Gibbs K, Hanka R, Walshe J M
Q J Med. 1978 Jul;47(187):349-64.
Radiocopper (64Cu, 67CU), given intravenously, has been used to study the pattern of excretion of copper in patients with presymptomatic, symptomatic and treated Wilson's disease, together with heterozygotes for the Wilson's disease gene and a control group of patients with a variety of neurological lesions mimicking Wilson's disease. Urine was collected for three periods after injection, 0 to 8 hours, 8 to 24 hours, at which time a test dose of penicillamine was given, and from 24 to 30 hours. Stable (endogenous) copper was also estimated on these samples and specific activity was determined. This was multiplied by a correction factor to allow for variations in dose and body weight. The findings for stable copper in urine were largely predictable. Controls and heterozygotes had the least copper excretion, the amounts rising in the presymptomatic to a peak in the symptomatic patients. Institution of therapy was associated with a fall in copper excretion pro rata with time. The most important radiochemical findings were as follows. Heterozygotes excreted less of the injected copper than controls both under basal conditions and after penicillamine. Presymptomatic patients excreted less radiocopper than heterozygotes after penicillamine although the excretion during the basal 24 hour period was very much greater. Patients with symptomatic Wilson's disease had by far the highest excretion of radiocopper in all three time periods which fell after treatment, pro rata with time, as had been found for stable copper. These results were subjected to computer analysis. There was no overlap between the various groups with the exception of a single control subject who had combined pyramidal and extrapyramidal system degeneration of obscure aetiology. This patient was classified by the computer study as 'heterozygote'. These findings lend further support to the hypothesis that the loss of a single gene for copper balance can be detected with a high degree of accuracy and also that presymptomatic patients can be selected from a sibship for prophylactic treatment without the risk of subjecting healthy heterozygotes to unnecessary and potentially hazardous long-term therapy.
静脉注射放射性铜（64Cu、67Cu）已被用于研究处于症状前期、有症状以及接受治疗的威尔逊病患者、威尔逊病基因杂合子以及一组患有各种模仿威尔逊病的神经病变的对照组患者体内铜的排泄模式。注射后分三个时间段收集尿液，0至8小时、8至24小时（此时给予青霉胺试验剂量）以及24至30小时。还对这些样本中的稳定（内源性）铜进行了估算，并测定了比活度。将其乘以一个校正因子以考虑剂量和体重的变化。尿液中稳定铜的结果在很大程度上是可预测的。对照组和杂合子的铜排泄量最少，在症状前期患者中排泄量增加，在有症状患者中达到峰值。开始治疗后，铜排泄量随时间成比例下降。最重要的放射化学研究结果如下。在基础条件下以及给予青霉胺后，杂合子排泄的注入铜比对照组少。症状前期患者在给予青霉胺后排泄的放射性铜比杂合子少，尽管在基础24小时期间的排泄量要大得多。有症状的威尔逊病患者在所有三个时间段内放射性铜的排泄量迄今为止都是最高的，治疗后随时间成比例下降，这与稳定铜的情况相同。这些结果进行了计算机分析。除了一名患有病因不明的锥体系统和锥体外系联合变性的单一对照受试者外，各个组之间没有重叠。该患者在计算机研究中被归类为“杂合子”。这些发现进一步支持了这样的假设，即可以高度准确地检测到单个铜平衡基因的缺失，并且可以从同胞中挑选出症状前期患者进行预防性治疗，而不会使健康的杂合子面临不必要的、潜在危险的长期治疗风险。
