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Background and purpose The severity of Wilson's disease ( WD) is linked to free copper accumulating in the liver and brain. Exchangeable copper (Cu EXC) is a new technique to determine plasmatic copper and is useful in the diagnosis of WD. It is hypothesized that it may also enable a good evaluation of extra-hepatic involvement and its severity. Methods Forty-eight newly diagnosed WD patients were prospectively evaluated using hepatic, neurological, ophthalmological and brain magnetic resonance imaging ( MRI) scores. Three phenotypic presentations were distinguished: pre-symptomatic, hepatic and extra-hepatic. Cu EXC was determined in addition to standard copper assays before decoppering therapy. Correlations between biological parameters and the different scores were determined and compared in the hepatic and extra-hepatic groups. Results Extra-hepatic patients had significantly higher Cu EXC values than those with the hepatic form ( P < 0.0001). The overall ability of Cu EXC to separate the two forms was satisfactory, with an area under the curve of 0.883 (95% confidence interval 0.771-0.996) and an optimal threshold for extra-hepatic diagnosis of 2.08 μmol/l (sensitivity 85.7%; specificity 94.1%). In extra-hepatic patients, Cu EXC was the only biological marker to be positively correlated with the Unified Wilson Disease Rating Score ( r = 0.45, P = 0.016), the Kayser−Fleischer ring score ( r = 0.46, P = 0.014) and the brain MRI score ( r = 0.38, P = 0.048), but it was not correlated with the hepatic score. Conclusions Exchangeable copper determination is useful when diagnosing WD as a value >2.08 μmol/l is indicative of the severity of the extra-hepatic involvement. In the case of purely hepatic presentation, atypical or mild neurological signs, it should encourage physicians to search for lesions in the brain and eyes. [ABSTRACT FROM AUTHOR]

An abstract of the article "Gadolinium chelates: pharmacokinetics during pregnancy" by B. Deloison and colleagues is presented.

Hepatotoxicity, predominantly cholestatic, is a rare adverse effect of gold salt therapy, which usually completely resolves within a few months. We report the case of a female patient treated for rheumatoid arthritis, who had gold salt overdose, and in whom acute cholestatic hepatitis occurred three weeks after beginning of therapy. Evolution of gold concentration was followed in plasma and urine, as well as in cutaneous and liver dry tissue. Liver biopsy showed marked inflammatory changes of interlobular bile ducts that evolved towards ductopenia, which was responsible for prolonged cholestasis still present 15 months later. In addition, sialadenitis with sicca syndrome was noted six months after onset of the disease. The mechanism of hepatotoxicity was probably immunoallergic since liver lesions were associated with hypersensitivity syndrome including dermatitis and blood and tissue eosinophilia. This is the first report of gold salt hepatotoxicity with histological demonstration of cholangitis followed by ductopenia.

T-cell prolymphocytic leukaemia (T-PLL) is a rare form of mature T-cell leukaemia that is generally resistant to conventional chemotherapy. Mice transgenic for MTCP1 develop leukaemia similar to human T-PLL, providing a model useful for testing therapeutics. We here evaluated the potential effectiveness of arsenic trioxide (ATO) in murine T-PLL. In vitro, ATO consistently reduced the viability of murine T-PLL cells at a clinically achievable concentration (1 micromol/l). The percentage of viable cells after 24 h was 77 +/- 4%, 56 +/- 6%, 31 +/- 7% with 0 micromol/l, 0.5 micromol/l and 1 micromol/l ATO respectively. ATO cytotoxicity was enhanced by ascorbic acid (125 micromol/l). Mice were then treated with ATO (5 microg/g/d intra peritoneally, 5 d per week) or saline for 4 weeks, starting 14 d after tumoral engraftment. The appearance of lymphocytosis and splenomegaly was delayed in the group treated with ATO and survival was significantly prolonged (mean survival in days: 57.6 +/- 0.8 for ATO versus 45 +/- 0 for saline, P < 10-4). No additional effect was observed in vivo by combining ATO with ascorbic acid (500 microg/g/d, 5 d per week, intra peritoneally). These findings provide support for clinical trials to test therapeutic effects of ATO for human T-PLL.