Standardization of glycated haemoglobin assays throughout the Northern region of England: a pilot study.

We describe a pilot study designed to assess the comparability of measurements of glycated haemoglobin among 15 laboratories in the North of England. We also evaluated a means of improving agreement and aligning results by referencing locally measured values to those obtained by the central biochemistry laboratory of the Diabetes Control and Complications Trial research group. Blood samples from 50 diabetic and non-diabetic subjects were analysed for glycated haemoglobin content in the participating and reference laboratories using a variety of routinely available methods. The mean CV for these results was 15.3% (95% confidence interval 14.0% to 16.5%). Using a regression equation relating a subset of seven of these results to their assigned reference values, a glycated haemoglobin index was calculated for all the other samples distributed. The mean inter-laboratory CV improved to 4.6% (95% confidence interval 4.0% to 5.1%), p<0.0001. The percentage bias of results from the reference method also improved from 15.1% (95% confidence interval 9.4 to 20.1) to 4.67% (95% confidence interval 4.05 to 5.25) after alignment, p<0.001. This study demonstrated that substantial method related differences between reported glycated haemoglobin results exist. These can be reduced using a simple calibration strategy in which data are correlated to an established method with associated extensive clinical interpretive value as established by the DCCT.

Emergency serum creatine kinase MB isoenzyme concentration in patients with suspected acute myocardial infarction.

We report the results of the introduction of a service which offered emergency measurement of serum creatine kinase MB isoenzyme concentration in patients admitted to hospital with suspected acute myocardial infarction and a non-diagnostic electrocardiogram. A retrospective study suggested that in such patients, a single admission measurement would have a diagnostic sensitivity of 70% and specificity of 100%. A prospective study employed a protocol which included repeat measurement after two hours where the initial measurement was low in samples taken less than six hours after the onset of symptoms. The prospective study showed that the service was welcomed by physicians, who employed the measurements appropriately as a supplement to, rather than substitute for, clinical judgement. In a continuing audit, 228 patients had an emergency measurement according to the agreed protocol. 79 of these had a discharge diagnosis of acute myocardial infarction. The diagnostic sensitivity and specificity of our emergency strategy were both 94%. The strategy led to the treatment with thrombolytic drugs of 73 patients who would not otherwise have been treated, 69 with a discharge diagnosis of acute myocardial infarction, and four with some other discharge diagnosis. The median time taken from requesting the analysis to reporting the result was 34 minutes. The costs and potential benefits of our strategy are discussed.

"Delfia" and "Amerlite": two sensitive nonisotopic immunoassay systems for assay of thyrotropin compared.

We assessed the LKB "Delfia" (time-resolved dissociation-enhanced lanthanide fluoroimmunoassay) and the Amersham "Amerlite" (enhanced luminescent immunometry) assays of thyrotropin in serum. Both assays are sensitive (respective detection limits: 0.02 and 0.04 milli-int. unit/L) and have very good within- and between-batch precision over a wide range of thyrotropin concentrations. Results by the two methods correlate well (r = 0.992); the regression equation is: Amerlite = 0.915 Delfia - 0.33 milli-int. unit/L. The standard curve for the Delfia assay was linear, but that for the Amerlite assay showed some deviation from linearity below 0.5 milli-int. unit/L. Both assays have a negative bias in comparison with radiolabeled immunoradiometric assays, as judged by results for samples from the Quality Assurance Scheme. Both assays discriminate well between hyper-, hypo-, and euthyroid subjects, and results for thyrotropin for most patients with nonthyroidal illness were within the euthyroid reference interval. Both assays are convenient to perform and are based on systems that provide a viable alternative to radioimmunoassay.

Use and misuse of a digoxin assay service.

In a study of the use of a digoxin assay service and its influence on clinical management 285 assay requests were audited over 12 weeks. For 67 (24%) there was no clear clinical indication for the request and for 140 the period between the last dose of digoxin being given and the blood sample being taken was either unknown or inappropriate. Treatment in 64 patients (22%) was changed after the assay result was received [corrected]. 24 of these changes bore no relation to the original clinical indication for requesting the assay, suggesting that such changes were based on the assay result alone. Of samples collected within six hours after the last dose, 15 of 69 (22%) led to a reduction in treatment compared with 10 of 116 (9%) taken after six hours (p less than 0.025), thereby highlighting the danger that incorrectly timed samples may lead to inappropriate clinical decisions.

Intact parathyroid hormone assay offers increased sensitivity over C-terminal assays in the study of parathyroid graft function.

Serum parathyroid hormone (PTH) levels in 6 patients who had received parathyroid tissue autografts were studied. Samples were taken from graft and non-graft arms both pre- and post-dialysis. Each sample was analysed using two PTH assays, one measuring C-terminal PTH and the other measuring the intact PTH molecule. For both pre- and post-dialysis samples an appreciably greater difference was seen between the graft and non-graft arms using the intact assay. A patient with suspected ectopic PTH production showed a very much reduced differential between the two sampling sites with both assays. We suggest that the intact PTH assay is of greater clinical utility in the localisation of ectopic glands and monitoring of graft function than the commonly used C-terminal assays.

Evaluation of the intact hormone assay in the study of parathyroid autograft function.

Parathyroid autograft function was studied using radioimmunoassay measuring intact parathormone (iPTH) and C-terminal PTH (C-PTH). Blood samples were taken from graft and non-graft arms pre- and post-dialysis. The intact assay showed an appreciably greater differential gradient pre- and post-dialysis than the C-terminal assay. We conclude that particularly in patients with chronic renal failure the intact assay is of greater value in monitoring graft function than the commonly used C-terminal assay. It may also be of value in distinguishing between graft overactivity and ectopic cervical parathyroid tissue in cases of recurrent hyperparathyroidism following apparently total parathyroidectomy and autotransplantation.

Plasma digoxin: assay anomalies in Fab-treated patients.

Using a variety of radioimmunoassay methods, plasma digoxin concentrations were measured in two patients before and after the administration of ovine Fab antibody fragments to remove the effects of digoxin. Gross method-dependent anomalies in the results due to in vitro drug interaction were observed. More widespread use of immunotherapy may invalidate data obtained by direct immunoassay techniques.