Results from a Ukrainian-US collaborative study: prevalence and predictors of respiratory symptoms among Ukrainian coal miners.

BACKGROUND: Underground coal mining is an expanding industry in Ukraine, yet little is known about the burden of respiratory disease among Ukrainian miners. METHODS: A Fogarty International Center-supported collaboration between researchers at the University of Illinois and the Institute of Occupational Health in Kyiv, Ukraine formed to improve capacity for conducting and monitoring medical surveillance among Ukrainian coal miners. A cross-sectional survey among a random sample of working and former miners was conducted; demographic, work, and health information were collected using a standardized questionnaire. Weighted prevalence rates were calculated and predictors of respiratory symptoms explored. RESULTS: Improvements in infrastructure, including spirometry and chest radiography testing, transformed medical surveillance among these miners. Results from the health study included that the prevalence of respiratory symptoms was higher among former compared to current miners (shortness of breath 35.6% vs. 5.1%; chronic bronchitis 18.1% vs. 13.9%, respectively). A statistically significant exposure-response relationship was observed between years mining and respiratory symptoms in former miners and between years mining at the coal face and respiratory symptoms among current miners. Evidence of downward bias from the healthy worker survivor effect was observed. CONCLUSIONS: This successful international collaboration built a sustainable infrastructure for conducting workplace medical surveillance and research. The resulting study was the first in the western literature to report on respiratory symptoms in this population; likely underestimation of disease rates due to selection and measurement biases was demonstrated. Efforts should continue to build this collaboration and to characterize and reduce respiratory illness among Ukrainian coal miners.

Tricyclic antidepressants in red cells and plasma: correlation with impaired intraventricular conduction in acute overdose.

OBJECTIVE: Tricyclic antidepressant levels in red blood cells and plasma in acute overdose and their association with cardiotoxicity were studied. METHODS: This was a prospective study in 15 patients with acute tricyclic antidepressant overdose. Tricyclic antidepressant parent compounds and metabolites were measured in red blood cells and plasma, and tricyclic antidepressant levels were correlated with ECG indexes of toxicity. RESULTS: Plasma levels of the parent compounds were higher than their red blood cell levels on admission (mean +/- SD, 691 +/- 409 and 337 +/- 220 ng/ml, respectively). Admission metabolite levels were higher in red blood cells than in plasma (264 +/- 180 and 190 +/- 164 ng/ml, respectively). QRS duration and the red blood cell levels of the metabolites were significantly correlated at the time of admission (r = 0.77, p < 0.01), as well as at 6 to 10 hours (r = 0.74, p < 0.01). CONCLUSIONS: In acute overdose, a shift of tricyclic antidepressants from plasma to red blood cells and increased levels of red blood cell metabolites reflect tissue redistribution of the drug. Tricyclic antidepressant red blood cell metabolites are the best markers for impaired intraventricular conduction.

Appraisal of lupus nephritis by renal imaging with gallium-67.

To assess the activity of lupus nephritis, 43 patients with systemic lupus erythematosus (SLE) were studied by gallium imaging. Delayed renal visualization 48 hours after the gallium injection, a positive result, was noted in 25 of 48 scans. Active renal disease was defined by the presence of hematuria, pyuria (10 or more red blood cells or white blood cells per high-power field), proteinuria (1 g or more per 24 hours), a rising serum creatinine level, or a recent biopsy specimen showing proliferative and/or necrotizing lesions involving more than 20 percent of glomeruli. Renal disease was active in 18 instances, inactive in 23, and undetermined in seven (a total of 48 scans). Sixteen of the 18 scans (89 percent) in patients with active renal disease showed positive findings, as compared with only four of 23 scans (17 percent) in patients with inactive renal disease (p less than 0.001). Patients with positive scanning results had a higher rate of hypertension (p = 0.02), nephrotic proteinuria (p = 0.01), and progressive renal failure (p = 0.02). Mild mesangial nephritis (World Health Organization classes I and II) was noted only in the patients with negative scanning results (p = 0.02) who, however, showed a higher incidence of severe extrarenal SLE (p = 0.04). It is concluded that gallium imaging is a useful tool in evaluating the activity of lupus nephritis.

A morbidity study of former pentachlorophenol-production workers.

Pentachlorophenol (PCP) is a pesticide that was once widely used for wood preservation. Commercial PCP contained impurities including higher chlorinated dibenzo-p-dioxins (CDDs) and chlorinated dibenzofurans (CDFs). We investigated the effects of occupational exposure to PCP and its CDD and CDF contaminants on the skin, liver, porphyrin metabolism, and central and peripheral nervous systems. In 1986 we conducted a medical survey of 366 workers who had been engaged in the production of PCP at a single plant between 1938 and 1978. The referent group consisted of 303 workers from the same plant who were not exposed to these or related compounds. Exposure was determined from computerized personnel records. The medical survey included an administered questionnaire, medical record review, physical examination by dermatologists, internists, and neurologists, and analysis of 24-hr urine for quantitative porphyrins among other tests. In this paper we present the results of analyses of the general health, chloracne, and porphyrin metabolism end points. The general health status of PCP workers was similar to unexposed workers, but 17.8% of PCP workers had evidence of current or past chloracne. PCP workers with chloracne had significantly higher mean urinary excretion of coproporphyrins (117. 0 vs. 90.6 microg/24 hr) than unexposed workers after controlling for potential confounders. Workers with chloracne who had worked with both PCP and polychlorinated biphenyls had significantly higher mean urinary excretions of hepta-, penta-, and coproporphyrins than unexposed workers. We conclude that occupational exposure to PCP is associated with chloracne and biochemical abnormalities which may persist years after exposure.

Hyperaluminemia in renal failure: the influence of age and citrate intake.

Following the occurrence of aluminum encephalopathy in four patients with chronic renal failure, we studied 34 azotemic patients seen during the same year and five volunteers who took varying combinations of aluminum hydroxide and an alkalinizing citrate (Shohl's) solution. We found that the four encephalopathic cases were older than the 34 azotemic patients (68 years +/- 14 SD, vs 50 +/- 13, p less than 0.05), had a higher mean serum aluminum value (727 micrograms/l +/- 320 vs 92 +/- 73, p less than 0.005), had taken more aluminum hydroxide (5 g/day +/- 0.9 vs 1.6 +/- 1.8, p less than 0.01), and more Shohl's solution (64 ml/day +/- 19 vs 20 +/- 29, p less than 0.01). In all 38 patients the serum aluminum values correlated directly with age (p = 0.01), aluminum hydroxide (p = 0.001) and concomitant citrate intake (p = 0.004). In the five healthy volunteers the 24-hour urinary aluminum excretion increased from a baseline of 22 micrograms +/- 19 SD to 167 +/- 109 (p = 0.05) during aluminum hydroxide intake, rising to 580 +/- 267 (p = 0.01) during the simultaneous intake of citrate and aluminum hydroxide. Corresponding serum aluminum values were 11 micrograms/l +/- 2 SD, 44 +/- 34 (p = 0.1), and 98 +/- 58 (p less than 0.05). Thus citrate seems to enhance aluminum absorption and may cause encephalopathy in patients with chronic renal failure, especially the elderly.

Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls in breast milk from two cities in Ukraine.

Substantial environmental pollution has been alleged in Ukraine, but little information is available to allow an assessment of the possible impact on humans. To help remedy this lack of information, it was of interest to investigate whether certain polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), or coplanar polychlorinated biphenyls (PCBs) were elevated in people from Ukraine. Samples of breast milk were obtained from 200 women from the cities of Kyiv and Dniprodzerzhinsk; Kyiv is the capital and Dniprodzerzhinsk is a highly industrialized city. The samples were combined into four pools by city and age, and analyzed for 7 PCDDs, 10 PCDFs, and 2 coplanar PCBs (126 and 169). The total of the measured PCDDs, expressed as toxic equivalent, ranged from 5.1 to 7.6 pg/g lipid; for PCDFs from 3.6 to 5.2, and for PCBs from 11 to 18 pg/g lipid. Results from the two cities were similar; older women had slightly higher concentrations than did younger women. Levels of these compounds seen in Ukraine were similar to or lower than those seen in other recent studies from European and Asian countries.

Collaborative research and research training through the "Family and Children of Ukraine" research program.

Family and Children of Ukraine, the Ukrainian component of the European Longitudinal Study of Pregnancy and Childhood, is a prospective, geographically-based study to evaluate pregnancy outcomes in 8,000 women in five cities in Ukraine and follow the cohort of births through 7 years of age. Family and Children in Ukraine has been the major collaborative research project for the University of Illinois' Fogarty-funded program, International Training and Research in Environmental and Occupational Health. This Fogarty program includes graduate training, U.S.-based training of visiting scientists, in-country training, and collaborative in-country research. Factors that have contributed to the success of the collaboration include: 1) its focus on the environmental health of mothers and children, which is a priority goal for both countries; 2) the adoption of an internationally-endorsed research protocol with strict quality-control criteria, specifically designed for international collaboration; 3) the establishment of an in-country data management center; and 4) the investment in a long-term research program rather than a short-term study. The major obstacles have been the difficult economic situation in Ukraine, which limits in-country research investment, and the difficulty in obtaining U.S. funding for an international research program.

Polycyclic aromatic hydrocarbons in placenta.

Concentrations of chrysene, benz [a] anthracene, benzo [a]-pyrene, benzo [b] fluoranthene, indeno [1,2,3-c,d] pyrene, dibenz [a,h] anthracene, and benzo [g,h,i] perylene were measured in placentas from 200 women from two cities in Ukraine, Kyiv and Dniprodzerzhinsk. The participants had no special exposures and were chosen from among subjects in an ongoing study of reproductive health. All seven of the polycyclic aromatic hydrocarbons (PAHs) were found in all placentas, with the sole exception of benzo [a] pyrene in one placenta. Chrysene was present at the highest concentrations, with median 1.38 ng/g dry weight. Dibenz [a,h] anthracene and benzo [g,h,i] perylene had the lowest concentrations; each had median 0.73 ng/g dry weight. Concentrations in Kyiv were slightly higher than those in Dniprodzerzhinsk, but the difference was significant only for dibenz [a,h] anthracene. Dibenz [a,h] anthracene and benzo [g,h,i] perylene increased significantly with maternal body mass index, but other PAHs showed no such pattern. Placentas from deliveries in autumn or winter had slightly but not significantly higher concentrations. Concentrations were not related to maternal age. There were too few smokers in the sample for meaningful evaluation. No associations were seen between any of the placental PAH concentrations and birth weight of the infant.

Detection of anticardiolipin antibody in patients with cocaine abuse.

Anticardiolipin antibody, an immunoglobulin that binds negatively charged phospholipids, is considered to be an in vitro inhibitor of clot-based coagulation procedures. We adapted an enzyme immunoassay using stationary cardiolipin antigen to compare anticardiolipin antibody activity in the plasma of 44 cocaine abusers with its activity in the serum of 72 blood donors and a sample of 203 random specimens from healthy volunteers. Activity of 20 of the 44 abusers and 43 of 203 random specimens exceeded the donor control reference range. Patients using intravenous cocaine were more likely to have elevated activity than those who inhaled (P less than 0.05). Of 7 patients who had seizures or thromboembolic disorders, 5 were anticardiolipin antibody positive. Enzyme immunoassay may have predictive value for ischemic disease in cocaine abusers.

Effects of nonparticipation in trauma center system on emergency department utilization.

The University of Illinois Hospital (UIH) serves an inner-city urban population in one of the highest crime rate districts in Chicago. On May 20, 1986, the city's Level I Trauma ordinance took effect with the University of Illinois Hospital declining to participate. To measure the impact of the ordinance on a nonparticipating hospital, we undertook a retrospective analysis of our trauma patient utilization statistics. Consecutive monthly patient census data of 71 months was compiled with emphasis on patient presenting complaints and related subspecialty evaluation. We observed significant decreases of patients presenting with head injuries, fractures, and animal bites as well as with major trauma, minor trauma, and general surgery hospital admission. The final disposition of the patients arriving by ambulance was consistent with the observed decrease in major traumatic conditions and in minor traumatic conditions. However, the mean number of patient presentations per day (ppd) admitted to regular medical or surgical beds decreased from 2.70 ppd to 2.30 ppd while the mean number of ppd sent home increased from 2.64 ppd to 3.49 ppd. These data suggest that loss of trauma center status designation has a profound effect on utilization of emergency departments not participating in the trauma system. Nonparticipation appears to be associated with a significant decrease in utilization rates for major and minor trauma patients and a significant increase in the number of patients discharged who had arrived by the Chicago Fire Department Paramedic System (CFD). This effect on the emergency department extends to utilization of inpatient services.

A wire reclamation incinerator as a source of environmental contamination with tetrachlorodibenzo-p-dioxins and tetrachlorodibenzofurans.

The authors investigated an outbreaks of unusual illnesses in humans and horses residing within 1.3 km of a wire reclamation incinerator. The study included site visits; medical and veterinary examinations; analyses of furnace ash, fly ash, soil, and biologic samples for air residues. Tetrachlorodibenzo-p-dioxins (TCDDs) and tetrachlorodibenzofurans (TCDFs) were discovered in furnace ash, fly ash, soil, horse fat, and horse liver samples.

Constraints on the enhancement of elimination of drugs with activated charcoal.

Both extracorporeal hemoperfusion through charcoal-containing columns and repeated oral administration of charcoal can accelerate clearance of some drugs or toxins from the systemic circulation. The efficacy of these 2 interventions is limited by a variety of factors, and the complex kinetic equations describing charcoal-induced clearance provide little practical clinical guidance about the potential efficacy of charcoal in accelerating clearance of a specific drug or toxin without previous empiric data. We derive here simple rules that place an upper limit on the maximal fraction of an absorbed dose of drug that can be removed (FRmax) by charcoal in terms of the volume of distribution (Vd), a parameter which is known for most drugs. For 4 h of hemoperfusion, a theoretical upper limit of FRmax is (1/Vd), where Vd is expressed in L/kg of body weight, and actual fractional removal (FR) will not exceed [1/(2 x Vd)]. Drug removal by 24 h of repeated po administration of charcoal exhibits similar relationships between FRmax and Vd, when charcoal-induced clearance derives primarily from removal of drug from blood perfusing in gastrointestinal mucosa. These relationships offer a simple means to evaluate the potential efficacy of acceleration of drug clearance by activated charcoal for drugs with a known value for Vd, and the relationships indicate that such interventions are impractical for drugs with very large values for Vd, such as tricyclic antidepressants.

Unusual occupational toxins.

Occupational and environmental medicine affords encounters with many unusual toxins, ranging from exotic metals to rocket fuels. Twelve of the most unusual industrial toxins are reviewed here and their clinical manifestations and treatments explored: acetonitrile, acrylonitrile, boron hydrides, dimethylaminopropionitrile, dimethylformamide, hydrazines, methyl isocyanate, 2-nitropropane, phosphine, Stalinon, tellurium, and vanadium.

Successful therapy of iron intoxication in pregnancy with intravenous deferoxamine and whole bowel irrigation.

We describe the successful treatment of a severely iron-poisoned adult patient in week 26 of gestation with 10.2 g deferoxamine administered iv over 14 h and whole bowel irrigation (2 L/h of polyethylene glycol-electrolyte solution/nasogastric tube for 12 h) with a good maternal outcome and no adverse effects on the fetus.

Treatment of ciguatera fish poisoning with amitriptyline and nifedipine.

Ciguatera fish poisoning is the most common fish poisoning in the United States. Symptoms involve the gastrointestinal, cardiovascular and neurological systems. No known treatment exists. We explore the therapeutic effect of amitriptyline in two patients and nifedipine in one patient. Amitriptyline demonstrated resolution of most symptoms except for heat/cold reversal in one patient and heat/cold reversal, pruritus and headache in the second patient. We then used nifedipine in the second patient and noted only the resolution of his headaches. We recommend further study of these agents for the treatment of ciguatera fish poisoning.

The price of gold: mercury exposure in the Amazonian rain forest.

Concern has surfaced over the recent discovery of human mercury exposure throughout the tropical rain forest of South America's Amazon River Basin. The probable source of mercury has been traced to gold mines located within the interior. The mining process involves the extraction of gold from ore by burning off a mercury additive, resulting in vaporization of elemental mercury into the surrounding environment. The purpose of this case series is to document mercury levels in miners and local villagers presenting with a history of exposure, or signs and symptoms consistent with mercury toxicity. Over a five year period (1986-91), the whole blood and urine mercury levels of 55 Brazilian patients demonstrating signs and symptoms consistent with mercury exposure were collected. Thirty-three (60%) of the subjects had direct occupational exposure to mercury via gold mining and refining. Whole blood mercury levels ranged from 0.4-13.0 micrograms/dL (mean 3.05 micrograms/dL). Spot urine levels ranged 0-151 micrograms/L (mean = 32.7 micrograms/L). Occupational mercury exposure is occurring in the Amazon River Basin. Interventions aimed at altering the gold mining process while protecting the workers and surrounding villagers from the source of exposure are essential. The impact of the gold mining industry on general environmental contamination has not been investigated.

Treatment of neuroleptic malignant syndrome with diphenhydramine.

A case report of a patient with neuroleptic malignant syndrome is described. Of note is the fact that both central and peripheral manifestations of the syndrome responded to diphenhydramine and suportive therapy alone. A brief review of therapy is also discussed.

Surveillance for carbon monoxide poisoning using a national media clipping service.

Using a novel method to review carbon monoxide (CO) exposures in the US, the role of CO detectors in prevention of CO-related deaths was studied. Using a national media clipping service, CO poisonings reported in the US were analyzed. The impact of CO detectors was investigated through nonfatal outcomes attributable to the presence of CO detectors and case fatality rate comparison among cities with and without CO detector ordinances. There were 4,564 CO exposures resulting in 406 (8.9%) fatalities. Of the exposures 2,617 (57.3%) occurred in the home, accounting for 374 (92.1%) deaths. Faulty heating systems constituted 2,540 (55.6%) exposures and 186 (45.8%) deaths, with alternate heating sources responsible for 389 (8.5%) exposures and 104 (25.6%) deaths. Cities with CO detector ordinances showed lower case fatality rates as reported in the media than those cities without ordinances (P <.001). There were 1,008 (24.2%) survivors who attributed their survival to the presence of a CO detector. A media clipping service provided insight into CO poisoning demographics. Despite its limitations, this tool may calibrate the positive impact of CO detectors on the prevention of CO-related deaths.

Use of the scan statistic to detect temporal clustering of poisonings.

The purpose of this study is to explore the use of the scan test to detect temporal clustering of poison control center data. We applied the scan test to a computerized data set consisting of all cases of carbon monoxide poisoning reported to our Poison Control Center in 1988. Using a time window of three days, the scan test identified three statistically significant temporal clusters. A review of case and climatologic data revealed that two of the clusters were due to family outbreaks and one was due to a sudden cold spell. We conclude that the scan test is a potentially useful surveillance tool which can be easily applied to poison control center data.

Inpatient theophylline toxicity: preventable factors.

OBJECTIVE: To identify preventable factors contributing to inpatient theophylline toxicity. DESIGN: Case series. SETTING: Tertiary care public hospital. PATIENTS: Forty consecutive adult inpatients (mean age, 56.5 years) with theophylline levels greater than 140 mumol/L (25.0 mg/L). MEASUREMENTS AND MAIN RESULTS: A retrospective chart audit was done. Toxicity was produced in 27 of 40 patients by inpatient or emergency department theophylline administration. Management errors found included delay (greater than 10 hours) in taking action from time toxic blood levels were drawn (20 patients), inappropriately high dosing of patients with congestive heart failure (17 patients), failure to recognize obvious symptoms (16 patients), recurrent toxicity (11 patients), additional emergency department treatment of already toxic patients (7 patients), overlap of intravenous and oral therapy (6 patients), patient discharged with no physician awareness of toxicity or dosage change (5 patients). CONCLUSIONS: A set of recurring management errors was identified as contributing to inpatient theophylline toxicity. Effective preventive mechanisms could have prevented most toxicity and associated morbidity. Theophylline's overall risk-benefit ratio in the inpatient setting may be less than that measured in well-controlled studies of the drug's efficacy because of these management errors.