Undetectable pregnancy-associated plasma protein-A in antenatal serum Down's syndrome screening: a case of assay interference.

Serum pregnancy-associated plasma protein-A (PAPP-A) is measured in Down's syndrome screening, routinely offered to women in pregnancy. We present the case of an undetectable pregnancy-associated plasma protein-A concentration on the PerkinElmer AutoDELFIA system where immunoassay interference was suspected. Investigations performed, including dilution and recovery studies and antibody-blocking tube incubations, all yielded serum pregnancy-associated plasma protein-A concentrations of <25 mU/L. Pregnancy-associated plasma protein-A was also undetectable on two alternative pregnancy-associated plasma protein-A assays. An experimental manual Delfia procedure suggested the site of interference was between the secondary antibody and the pregnancy-associated plasma protein-A molecule. This case of negative interference in the PerkinElmer pregnancy-associated plasma protein-A assay produced a falsely high Down's syndrome risk that might have led to an unnecessary invasive procedure with the potential for fetal loss. This highlights the need for Down's syndrome screening laboratories to be vigilant to immunoassay interference due to the significant impact of the results on patient decision outcome.

The penetration of Sorbinil, an aldose reductase inhibitor, into lens, aqueous humour and erythrocytes of patients undergoing cataract extraction.

Two studies to investigate the penetration of the aldose reductase inhibitor, Sorbinil, were conducted. In the first study, 24 diabetic patients undergoing intracapsular extraction were randomised into three groups on a double masked basis. In the week immediately preceding the operation, all patients were requested to take two capsules daily before breakfast. Each capsule contained 200 mg Sorbinil, 100 mg Sorbinil, or a placebo. On measuring Sorbinil levels in lens, plasma and erythrocytes using HPLC, three clearly defined groups of patients were obtained. In one group no Sorbinil was detected, in the second group there were moderate levels of Sorbinil, while the third group had significantly higher levels of Sorbinil. The ratio of erythrocyte/plasma Sorbinil was 0.225, while the ratio for lens/plasma was 0.7, for both groups where Sorbinil was detected. In a second study, 20 patients were treated topically with a single dose of 0.5 mg ophthalmic Sorbinil at times ranging from 0-14 hr preoperatively. Sorbinil was detected in both lens and aqueous. Transport into the lens was complete within about 2 hr, and although aqueous levels were negligible after 6 hr, Sorbinil persisted up to 14 hr in the lens. Three out of 16 patients taking Sorbinil orally developed a maculopapular rash with pyrexia approximately 8 days after commencing the drug. No side effects were noted in any patients given the topical ophthalmic preparation.

NADPH-oxidising activity in lens and erythrocytes in diabetic and nondiabetic patients with cataract.

Levels of lens aldose reductase, aldehyde dehydrogenase activity, and erythrocyte NADPH-oxidising (or glyceraldehyde reductase) activity were determined in 17 diabetic and 16 nondiabetic patients undergoing cataract extraction. Lens aldose reductase and aldehyde dehydrogenase activities were significantly lower in diabetics than in nondiabetics. Both enzymes showed significant inverse correlations with grouped HbA1c and fasting blood glucose levels. By contrast, erythrocyte NADPH-oxidising activity showed a significant positive correlation with grouped HbA1C. It is suggested that a direct effect of the glycaemic status on the lens enzymes is masked by a loss of enzymes secondary to the development of cataract. It is not yet possible to say whether erythrocyte NADPH-oxidising activity can be used to monitor aldose reductase activity in the lens or other tissues in clinical trials of aldose reductase inhibitors.