Mercury poisoning occurred after the acute, prolonged exposure of 53 construction workers to elemental mercury. Of those exposed, 26 were evaluated by clinical examination and tests of neuropsychological function. Patients received treatment with chelation therapy in the first weeks after exposure. Eleven of the patients with the highest mercury levels were followed in detail over an extended period. Observations included the evaluation of subjective symptoms of distress, using the 'Symptom Check List 90-Revised' (SCL-90R) and tests of visual-motor function such as 'Trailmaking Parts A and B', 'Finger Tapping', 'Stroop Colour Word Test' and 'Grooved Pegboard.' On day 85 ± 11 (mean±s.d.) after exposure, these 11 men again received either 2,3-dimercaptosuccinic acid (DMSA) or N-acetyl-D, L-penicillamine (NAP) in a short-term study designed to compare the potential to mobilize mercury and the incidence of drug-induced toxicity of these two chelating agents. Rapidly resolving metal fume fever was the earliest manifestation of symptoms. CNS symptoms and abnormal performance on neuropsychological tests persisted over the prolonged period of follow-up. There were significant correlations between neuropsychological tests and indices of mercury exposure. Serial mercury in the blood and urine verified the long half-life and large volume of distribution of mercury. Chelation therapy with both drugs resulted in the mobilization of a small fraction of the total estimated body mercury. However, DMSA was able to increase the excretion of mercury to a greater extent than NAP. These observations demonstrate that acute exposure to elemental mercury and its vapour induces acute, inorganic mercury toxicity and causes long-term, probably irreversible, neurological sequelae.

No abstract

Autoradiographic studies have shown that the liver accumulates endothelin. High-affinity binding sites for endothelin have been identified on rat liver plasma membranes. We investigated the role of endothelin isopeptides as mediators of cholestasis with isolated rat liver perfused by a recirculating solution of buffer and blood. These studies demonstrated that endothelin-1, as measured by means of radioimmunoassay, was cleared from the perfusate by the liver and that the liver concentrated both endothelin-1 and endothelin-3 in bile. Addition of endothelin-1 to the liver perfusate solution increased the concentration of endothelin-3 measured in the perfusate, suggesting that endothelin-1 caused release or secretion of endothelin-3. Both endothelin-1 and endothelin-3 at 5 nmol/L caused almost complete cessation of bile flow, but this effect was more prolonged after endothelin-1 than after endothelin-3 administration. Because it has been reported that cyclosporine increases endothelin levels, we studied the interaction of these two compounds. Cyclosporine (100 mumol/L) also produced cholestasis. Endothelin-3 secretion in bile, however, was decreased in livers perfused with cyclosporine compared with secretion in controls. Simultaneous addition of endothelin-1 and cyclosporine that on their own were not significantly cholestatic produced cholestasis. In conclusion, endothelin is a potent cholestatic agent secreted and excreted by the liver. It may potentiate the cholestatic action of cyclosporine.

Exposure to elemental mercury vapour is known to influence renal function; however, severe renal disease has not been consistently identified. Eleven men were evaluated for renal disease after acute, massive mercury poisoning. Significant hyperchloraemia was identified in this group of patients and a reversible renal tubular defect was suggested by low normal serum bicarbonate, a normal serum anion gap and a positive urinary anion gap. The only other evidence of renal dysfunction was transient, mild proteinuria in one of the 11 patients. During this same time period, neuropsychological impairment was identified on a test of cognitive and visual-motor function, 'Trailmaking B', in seven of the 11 patients. Additionally, dysuria and ejaculatory pain occurred without evidence of urological disease. These complaints were more frequent in those patients with impairement on 'Trailmaking B' suggesting a neurological basis for these symptoms. The findings of this study support earlier observations that the brain rather than the kidney is the critical target organ after elemental mercury vapour exposure.