Changes in compensation for occupationally induced bladder cancer.

faulty copper genes (almost always the result of consanguineous marriage) causes Wilson's disease. Heterozygotes are clinically well but may show some of the biochemical abnormalities. Excess copper damages first the liver and then as copper is released from the dying hepatocytes it affects the brain, eyes, kidneys, bones and joints, and possibly the parathyroid glands.8 The definitive biochemical signs are, firstly, a low plasma concentration of caeruloplasmin, usually but not always below 200 mg 1, with low serum concentrations of copper (less than 12 6 mmol 1 (80 mtg 100 ml)).9 Secondly, the urinary copper excretion is high. (A high urinary output of copper is also, however, seen in biliary cirrhosis.10) Thirdly, the copper content of the liver is raised and histological examination of biopsy specimens shows fine fat droplets, nuclear vacuoles, and a positive stain for copper. Fourthly, there is an overall diminution of copper incorporation into caeruloplasmin and a prolonged turnover of body copper. And, finally, rusty brown Kayser-Fleischer rings near the limbus of the eye are said to occur in all cases with neurological damage." Over the past 30 years treatments for Wilson's disease have been largely developed by Walshe.'2 13 He began with injections of the chelating agent BAL (British-as opposed to Russianantilewisite; dimercaprol) and then in 1956-7 developed oral treatment with penicillamine-a metabolite of penicillin of no previous importance-and showed that this effectively "decoppered" six patients with Wilson's disease. More important, clinical improvement, though sometimes slow, was spectacular. Renal tubular defects, liver disease, and neurological problems-and the CT scan abnormalities-are all reversed.'4 Treatment with pencillamine needs to be continued for life, and mild or severe sensitivity reactions are not uncommon. Patients who develop a rash, leucopenia, fever, a lupus-like syndrome, or the nephrotic syndrome may need to have the dose reduced, or treatment with cortisone, or the drug may have to be withdrawn. If penicillamine cannot be tolerated other effective treatments are fortunately available, the most satisfactory ofwhich is triethylene tetramine dihydrochloride." Large doses of zinc by mouth also result in a negative copper balance.'6 Our advances in the understanding of Wilson's disease have been spectacular over the past 70 years: over 1000 publications on the topic have appeared.' All too often, however, we are missing the diagnosis or making it too late.