Mortality among plutonium and other radiation workers at a plutonium weapons facility

Mortality among 5,413 white males who were employed for at least two years at a plutonium weapons facility was investigated to measure risks from exposures to low levels of plutonium and external radiation. When compared with US death rates, fewer deaths than expected were found for all causes of death, all cancers, and lung cancer. No bone cancer was observed. An excess of brain tumors was found for the cohort in general. Elevated rate ratios for all causes of death and all lymphopoietic neoplasms were found when employees with plutonium body burdens greater than or equal to 2 nCi were compared with those with body burdens less than 2 nCi, while accounting for age, calendar period, and induction time. Increased rate ratios were also found for esophageal, stomach, colon, and prostate cancers, and for lymphosarcomas and reticulum cell sarcomas. No elevated rate ratios were noted for bone and liver cancers. When employees with cumulative exposures greater than or equal to 1 rem were compared with those with exposures less than 1 rem, elevated rate ratios were found for myeloid leukemia, lymphosarcoma and reticulum cell sarcoma, liver neoplasms, and unspecified brain tumors. No overall dose-response relationships were found for plutonium or external radiation exposures. Standardized rate ratios increased, however, as plutonium body burden levels increased for all causes, all cancers, and digestive cancers at five years induction time. Standardized rate ratios also increased as external radiation exposure categories increased for all lymphopoietic cancers and unspecified brain tumors for a two-year induction period. With the exception of analyses of combined categories of death, and perhaps of lung cancer, confidence limits were wide, indicating limited precision. Nevertheless, these findings suggest that increased risks for several types of cancers cannot be ruled out at this time for individuals with plutonium body burdens of greater than or equal to 2 nCi. Plutonium-burdened individuals should continue to be studied in future years.     

Vein patch versus primary closure for carotid endarterectomy. A randomized prospective study in a selected group of patients

During a 4-year period, 136 patients undergoing 152 carotid endarterectomies consented to be randomized to primary or saphenous vein patch closure of the arteriotomy. At operation, before randomization, careful assessment of arterial dimensions and anatomy was made. Patients who had an internal carotid artery (ICA) diameter less than 5 mm, arteriotomy extending more than 3 cm beyond the origin of the ICA, or tortuous or kinked ICAs were not randomized; they received obligatory vein patch closure (necessary in 20% cases). All patients were followed up every 3 months for 1 year and every 6 months thereafter with duplex scanning, ocular pneumoplethysmography, and neurologic assessment. The incidence of atherosclerotic risk factors was equal in the groups and all except one of the patients were male. Perioperative morbidity was not significantly different among those having primary closure (n = 60), saphenous vein patch closure (n = 62), and obligatory vein patch closure (n = 30). Operative time among patients having primary closure (122 +/- 4 minutes) was significantly less (p less than 0.001) than among those having saphenous vein patch closure (150 +/- 3 minutes). Three perioperative strokes were evenly distributed among the groups (2% for all procedures); no deaths and no acute postoperative occlusions occurred. Recurrent disease occurred in 12.9% of patients having saphenous vein patch closure compared with its occurrence in 1.7% of those having primary closure (p less than 0.05). However, most recurrences were moderate stenoses (25% to 50% diameter reduction), all were smooth-surfaced, and none required a second operation. All except one of the recurrences among those patients with saphenous vein patch closure were in the bulb and the origin of the ICA; two had evidence of regression. This finding suggested that thrombus layering in the dilated part of the saphenous vein patch reconstruction was the cause. This study demonstrates that in men with carotid arteries of predetermined minimal dimensions undergoing carotid endarterectomy routine saphenous vein patch closure does not produce superior results, is associated with a higher incidence of early recurrence, and increases operative time. In selected patients with anatomic risk factors for recurrent disease or acute postoperative occlusion, saphenous vein patch closure is appropriate.     

Visual hallucinations on eye closure associated with atropine toxicity. A neurological analysis and comparison with other visual hallucinations

Visual hallucinations of remarkable intensity began shortly after intravenous atropine and persisted for 11 days. They were present only when the eyes were closed and were associated with heightened dreaming and disturbed sleep. The patient remained lucid and described his experiences to his attendants. Our patient's hallucinations bore some resemblance to hypnagogic hallucinations and this became the basis for the hypothesis that the hallucinations originated in the sleep-dream system of the brain stem. It is speculated that a similar site--a metabolic locus minoris resistentiae may play a part in other types of visual hallucinations and in delirium.     

Physiologically based pharmacokinetic modeling of the pregnant rat: a multiroute exposure model for trichloroethylene and its metabolite, trichloroacetic acid

A physiologically based pharmacokinetic (PB-PK) model was developed to describe trichloroethylene (TCE) kinetics in the pregnant rat exposed to TCE by inhalation, by bolus gavage, or by oral ingestion in drinking water. The kinetics of trichloroacetic acid (TCA), an oxidative metabolite of TCE, were described by a classical one-compartment pharmacokinetic model. Among the required model parameters for TCE, partition coefficients (PCs) and kinetic constants for oxidation were determined by vial equilibration and gas uptake methods, respectively. The fat:blood PC was 33.9; the blood:air PC was 13.2; and the fetal tissue:fetal blood PC was 0.51. TCE was readily metabolized with high substrate affinity. In naive and pregnant female rats the maximum velocities of oxidative metabolism were 10.98 +/- 0.155 and 9.18 +/- 0.078 mg/kg/hr, while the estimated Michaelis constant for the two groups of rats was very low, 0.25 mg/liter. The first-order rate constant for oral absorption of TCE from water was 5.4 +/- 0.42/hr-1 in naive rats. With TCA, the volume of distribution (0.618 liter/kg) and the plasma elimination rate constant (0.045 +/- 0.0024/hour) were estimated both from intravenous dosing studies with TCA and from an inhalation study with TCE. By comparison of the two routes of administration, the stoichiometric yield of TCA from TCE was estimated to be 0.12 in pregnant rats. To develop a data base for testing the fidelity of the PB-PK model, inhalation and bolus gavage exposures were conducted from Day 3 to Day 21 of pregnancy and a drinking water exposure from Day 3 to Day 22 of pregnancy. Inhalation exposures with TCE vapor were 4 hr/day at 618 ppm. The TCE concentration in drinking water was 350 micrograms/ml and the gavaged rats received single daily doses of 2.3 mg TCE/kg. Time varying physiological parameters for compartment volumes and blood flows during pregnancy were obtained from the published literature. Using the kinetic parameters determined by experimentation, TCE concentrations in maternal and fetal blood and TCA concentrations in maternal and fetal plasma were predicted from the PB-PK model by computer simulation and compared favorably with limited data obtained at restricted time points during pregnancy for all three routes of exposure. On the basis of the PB-PK model, fetal exposure to TCE, as area-under-the-curve, ranged from 67 to 76% of maternal exposure. For TCA the fetal exposure was 63 to 64% of the maternal exposure. The fetus is clearly at risk both to parent TCE and its TCA metabolite.(ABSTRACT TRUNCATED AT 400 WORDS)     

COMMUNITY PARTICIPATION OR COMMUNITY MANIPULATION? A CASE STUDY OF THE ILLAWARRA CANCER APPEAL-A-THON

Fashion parades, balls, raffles, and weekly deductions from thousands of workers' pay packets were integral to success of the Cancer Appeal-a-thon in the Illawarra region. In 1986–87 the Illawarra community was induced to contribute $1.5 million in order to purchase a linear accelerator for the Wollongong Hospital. The community agreed that a radiotherapy machine was the number one health service priority for the region. Or did it? Application of Alford's structural interests framework to this case-study reveals how failure to examine power relations between medical monopolizers, health care rationalizers and community participants results in an inability to recognise that alternative community needs — for cancer prevention, domiciliary care, or alternative therapies — might be unarticulated or unobservable, and in an inability to ask whether the community may be mistaken about, or unaware of, its own health needs. Specifically, the paper argues that, ‘community needs’ are easily manipulated or distorted by powerful interest groups and that the political context within which community needs are recognized, articulated and mobilized is the most important issue for community participation in the health policy-making process.     

Bupropion and nicotine patch as smoking cessation aids in alcoholics.

This is a double-blind placebo-controlled study of sustained-release bupropion as a smoking cessation aid in alcoholics undergoing treatment for their alcoholism. Participants (N=58) were enrolled within 1 week of entry into alcohol treatment from community and Veterans Affairs Substance Use Disorder programs. All participants received nicotine patch and were invited to attend a smoking cessation lecture and group. Cigarette smoking and alcohol outcomes were measured at 6 months. Bupropion when added to nicotine patch did not improve smoking outcomes. One third of participants on bupropion reported discontinuing the drug during weeks 1-4. Participants reported cigarette outcomes with nicotine patch that are similar to those seen in the general population. All study participants significantly reduced cigarette use. Comorbid affective disorder or antipersonality disorder did not affect outcomes. Alcohol outcomes were improved in those who discontinued cigarettes.