Drug screening: ethical guidelines.
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Drug Evaluation, Preclinical↗
Biomedical subjects
K Kreiss
Publications and source records attributed to K Kreiss.
Approaches to assessing pulmonary dysfunction and susceptibility in workers.
Indices of the maximal forced expiration are the most widely adopted method of screening for occupational lung disease because of their ease of measurement, employee acceptability, and reproducibility. However, these indices may lack sensitivity, specificity, or validity in detecting cases of some occupational lung diseases at asymptomatic stages when intervention may affect outcome. In populations at increased risk for occupational asthma, pneumoconiosis, or hypersensitivity pneumonitis, three other types of screening are being evaluated in field settings: tests for bronchial hyperreactivity, barriers to diffusion, and abnormalities in gas distribution in the lung. The potential methods of screening--cold air challenge, methacholine challenge, peak flow logs, diffusing capacity, and single breath nitrogen tests--await clinical trials in industrial settings to evaluate whether early case finding of susceptible subjects can result in prevention of morbidity.
Cold Temperature↗
Studies on populations exposed to polychlorinated biphenyls.
Mean serum levels of polychlorinated biphenyls (PCBs) in U.S. population groups without occupational exposure to PCBs are usually between 4 and 8 ng/mL, with 95% of individuals having serum PCB measurements of less than 20. Subpopulations consuming fish taken from contaminated waters, such as Lake Michigan and near Triana, AL, have mean serum PCB levels several times those found in other general population groups and ranges that extend into concentrations found in industrial populations involved in capacitor manufacture. Two studies of general populations and several studies of industrial workers have demonstrated associations of PCBs with various serum lipids and liver enzyme levels. Six groups of investigators have found associations between PCB or chlorinated pesticide levels and blood pressure. Research efforts are needed in clarifying determinants of serum-adipose partition ratios; the utility of urinary porphyrins as a measure of subclinical hepatic effects; human metabolites and excretion of chlorinated hydrocarbons; and the relation, if any, between blood pressure and organochlorine compounds when controlled for confounding variables. Established cohorts, such as those in Triana, Lake Michigan sportsfishers, the Michigan PBB cohort, residents of farms with PCB-lined silos, and occupational groups, could all be studied further with attention to these research questions.
Adolescent↗
Risk factors for victimization during the 1980 riot at the Penitentiary of New Mexico.
The New Mexico Penitentiary riot of February 2, 1980, resulted in death for 33 inmates at the hands of their fellow prisoners, and the hospitalization of 62 inmates for treatment of drug overdose or trauma. A case-control study of dead and hospitalized inmates was conducted to determine risk factors for victimization. Twelve (12.5%) of the 96 inmates housed in the protective custody unit were killed, compared with an overall penitentiary death rate of 2.9% (p = 0.0003). These 12 individuals were similar to the general inmate population with respect to age, race, years of education, crimes, time served, and prison rule infractions committed. In contrast, the 21 homicide victims housed in other areas were younger and had committed significantly greater numbers of rule infractions during incarceration. Prisoners hospitalized for drug overdose, but not those hospitalized for traumatic injuries, could be differentiated from the remaining prison population by increased convictions for homicide and higher prison infraction rates. Inmates in protective custody were targeted selectively for death; other subgroups of victims of violence appear to share characteristics often associated with perpetrators of violence.
Adult↗
The assessment of human exposure to radionuclides from a uranium mill tailings release and mine dewatering effluent.
This study provides an assessment of human exposure to radiation from a river system contaminated by radionuclides of the 238U decay series released through a dam break at a uranium mill tailings pond and by the continuous discharge of dewatering effluent from 2 uranium mines. The in vivo analyses of radionuclides in 6 Navajo Indians who lived near the river indicate no detectable elevations above background concentrations. Dose estimates for inhalation of suspended river sediment indicate a maximum annual 50-yr dose commitment of 204 mrem to the endosteum. Estimates of doses (50-yr dose commitments) from the ingestion of livestock range between 1 mrem (to liver) and 79 mrem (to bone) suggest that the major contribution to human exposure is from mine dewatering effluent that has been continuously released into the river system for many years. Although the estimated exposures do not exceed existing state or federal regulations, their magnitude justifies further measurement of radionuclides in animals and in the natural environment and the consideration of strategies to reduce radiation exposure to humans and animals.
Accidents, Occupational↗
An outbreak of amebiasis spread by colonic irrigation at a chiropractic clinic.
From June 1978 through December 1980, at least 36 cases of amebiasis occurred in persons who had had colonic-irrigation therapy at a chiropractic clinic in western Colorado. Of 10 persons who required colectomy, six did. Of 176 persons who had been to the clinic in the last four months of 1980, 80 had received other forms of treatment. Twenty-one per cent of the colonic-irrigation group had bloody diarrhea, as compared with 1 per cent of the non-irrigation group (P = 0.00013). Thirty-seven per cent of the colonic-irrigation group who submitted specimens had evidence of amebic infection on either stool examination or serum titer, as compared with 2.4 per cent in the non-irrigation group (P = 0.00012). Persons who were given colonic irrigation immediately after a person with bloody diarrhea received it were at the highest risk for the development of amebiasis. Tests of the colonic-irrigation machine after routine cleaning showed heavy contamination with fecal coliform bacteria. The severity of disease in this outbreak may have been related to the route of inoculation.
Adult↗
Association of blood pressure and polychlorinated biphenyl levels.
The geometric mean serum level of polychlorinated biphenyls (PCBs) of 458 persons in a communitywide study was 17.2 microgram/L, with 80% to 90% having levels within the range found in other community groups. As a dependent variable, PCB levels were found to be positively related to age, even when controlled for all other variables associated with PCB level: sex, local fish consumption, obesity, serum cholesterol level, and alcohol consumption. No major point source of PCB contamination was found, and fish taken in the drainage of a major population center had mean PCB levels below the current enforceable Food and Drug Administration tolerance of 5 mg/kg. As an independent variable, serum PCB levels were positively associated with gamma-glutamyl transpeptidase level, serum cholesterol level, and measured blood pressure. The PCB-blood pressure association, which was independent of age, sex, body mass index, and social class, must be confirmed in other exposed populations.
Alabama↗
Cross-sectional study of a community with exceptional exposure to DDT.
The geometric mean level of total DDT in serum samples (76.2 ng/mL) from 499 persons living downstream from a defunct DDT-manufacturing plant was several times the national geometric mean (15.0 ng/mL). DDE isomers, metabolites of DDT, accounted for an average of 86.7% of total DDT. Total DDT levels increased with age, even when controlled for other independent variables also significantly associated with DDT: race, sex, fish consumption, years of residence, socioeconomic status, alcohol consumption, and serum triglyceride levels. Fish consumption, the second strongest determinant of DDT level, had one third the predictive power of age. Total DDT levels were not associated with specific illness or ill health. However, total DDT levels were positively associated with levels of serum cholesterol, triglyceride, and gamma-glutamyl transpeptidase. The finding that serum DDE levels increase with age suggests that no equilibrium in body burden has been reached or that pharmacokinetics or serum/adipose partition may vary with age.
Adolescent↗
Alcohol consumption and high-density-lipoprotein cholesterol.
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Adolescent↗
Clinical epidemiology of occupational neurotoxic disease.
Occupational exposures to neurotoxic chemicals have produced large outbreaks of illness in chemical and pesticide workers worldwide. Outbreaks of occupational neurologic disease in the United States have included (1) the Kepone episode in Hopewell, Virginia, in which 76 workers at a pesticide plant producing the chlorinated hydrocarbon insecticide, Kepone, developed a previously unrecognized syndrome of nervousness, tremor, ataxia, weight loss, opsoclonus, pleuritic and joint pain, and oligospermia; (2) an outbreak of 104 cases of autonomic neuropathy in polyurethane foam workers in Marblehead, Massachusetts, manifest principally by urinary bladder dysfunction, which followed exposure to a new catalyst, dimethylaminopropionitrile (DMAPN); and (3) an outbreak of acute mixed motor and sensory neuropathy in 48 plastic fabric workers in Columbus, Ohio, exposed to the solvent methyl butyl ketone (MBK). These outbreaks underscore the vulnerability of chemical workers to neurotoxins. In addition, occurrence of these large, easily detectable epidemics suggests that many more smaller clusters and single cases of neurologic disease of undetermined origin, particularly in younger adults, may be caused by exposure to occupational or to other toxic chemicals. Detection of the etiology of chemically induced neurologic illness requires a high index of suspicion and careful ascertainment of occupational history.
Adult↗
Serial PBB levels, PCB levels, and clinical chemistries in Michigan's PBB cohort.
Half of a cohort of 3683 Michigan residents exposed to polybrominated biphenyls (PBBs) in 1973 and 1974 had 2 serum PBB determinations at a 1- or 2-yr interval. The median decrease in serum PBB levels during both 1- and 2-yr intervals was 1 microgram/L. The geometric mean serum polychlorinated biphenyl (PCB) level (6.3 microgram/L) exceeded that of PBB (4.1 micrograms/L), although the range of PCB levels (smaller than 1-57 microgram/L) was narrower than that of PBB levels (smaller than 1-3150 micrograms/L). Mean PCB and PBB levels were higher for males, and mean PCB levels increased with age. In a subgroup with higher-than-average PBB levels, serial clinical chemistry tests during 4 different years showed no consistent significant correlation with serum PBB levels. Tests with greater sensitivity and specificity for hepatic microsomal enzyme induction and thyroid status are needed in future evaluations of the most highly exposed subgroup of the cohort.
Adolescent↗
Neurologic evaluation of a population exposed to arsenic in Alaskan well water.
One hundred forty-seven persons exposed to arsenic from well water were evaluated by neurologic examination and nerve conduction studies. Total arsenic concentrations in well water ranged from 1 to 4781 micrograms/L and from 6 to 4964 micrograms/L in urine; a calculated index of arsenic ingestion ranged from 1 to 4521 micrograms/day. No dose-response relationship existed between arsenic ingestion and symptoms or physical findings compatible with peripheral neuropathy. Five of six persons with symptoms or physical findings suggestive of sensory neuropathy had normal nerve conduction velocities. Thirteen persons with elevated arsenic ingestion but no signs or symptoms of neuropathy had one or more abnormal nerve conduction velocities. No dose-response relationship, however, existed between arsenic ingestion and nerve conduction velocities. The authors concluded that arsenic ingestion from well water at the concentrations found in this Alaskan community did not result in clinical or subclinical neuropathy.
Adult↗
An evaluation of the incidence of work-related asthma in the United States.
The objective of the study was to estimate the incidences of physician-diagnosed cases of work-related asthma (WRA) in Michigan and the entire United States. The statewide surveillance system for WRA in Michigan receives reports primarily from three sources: physicians, hospital discharge data, and worker's compensation claims. Knowledge of the overlap in reports from these sources was used in conjunction with capture-recapture methods to estimate the total number of diagnosed cases of WRA, and incidence rates were calculated using the estimated number of civilian employees in Michigan as the population at risk. For the entire United States, the product of a national incidence rate for asthma among adults and estimates of the proportion that is work-related was used. A total of 933 cases of WRA were reported to the Michigan surveillance program during 1988-1995, of which 904 were reported by at least one of the three main sources and equaled an average incidence of 27 cases/10(6)/year. This estimate was less than the range of estimates 58 to 204 cases/10(6)/year in Michigan arrived at using the capture-recapture methods. The national estimates of WRA ranged from 63 to 441 cases/10(6)/year. The authors' indirect estimates are closer to estimates from Canada, Sweden, and Finland than most existing direct estimates in the United States, but probably still underestimates the magnitude of WRA incidence because of the limitations of physician recognition of the work-relatedness of asthma among adults.
Adult↗
Immunologic evaluation of occupational lung disease.
Many inhaled agents in the workplace can induce immunologic responses. Given the current state of clinical immunology, this article focuses on how to detect the body's response to those inhaled agents that behave as antigens. First the types of immunologic mechanisms that are activated in occupational lung disease are discussed, and the tests that reflect those states of immunologic activation. The second part of the article reviews major classes of occupational lung diseases and the immunologic tools that are available in making specific diagnoses.
Antibody-Dependent Cell Cytotoxicity↗
The epidemiology of building-related complaints and illness.
The recent epidemiology of major building-related complaints and illness is summarized. The variety of symptoms that have been attributed to building environments in sick building syndrome and in building-related illness are described, including their likely pathophysiology and their implications for remedial action and prevention.
Denmark↗
Neurological dysfunction of the bladder in workers exposed to dimethylaminopropionitrile.
Neurogenic bladder dysfunction, characterized by hesitancy, need to strain, decreased stream, and increased duration of urination, developed in 104 (63%) of 166 employees working in the manufacture of polyurethane foam. Highest rates of illness (69%) occurred in production workers, and no illness occurred in office or warehouse workers. Onset of the epidemic coincided with introduction of a catalyst, dimethylaminopropionitrile (DMAPN), and monthly case incidence rates increased as DMAPN use increased. Outbreak ceased abruptly when DMAPN use was stopped. Of eight patients who underwent neurourologic testing during recovery, seven lacked either detrusor reflex or normal sensation of bladder filling; seven had a subclinical sensory abnormality; three had prolonged sacral-evoked responses; and two of these three had limb motor neuropathies. Dimethylaminopropionitrile is unique among known neurotoxins in producing urinary symptoms more frequently than limb nerve symptoms.
Adult↗