Diabetes control and complications: the role of glycated haemoglobin, 25 years on.

The long-term complications of diabetes have major consequences for individual subjects and growing healthcare delivery and cost implications for society. Evidence for the benefits of good glycaemic control, as monitored by glycated haemoglobin measurements, has been developed in the 25 years since they were introduced to the point where HbA(1c) assays play central roles in patient management, clinical guidance and audit, and clinical trial design. In this review this evidence is examined and three classes of uncertainty identified that diminish confidence in the effectiveness of these roles for HbA(1c).

Clinical pathology accreditation: standards for the medical laboratory.

This article describes a new set of revised standards for the medical laboratory, which have been produced by Clinical Pathology Accreditation (UK) Ltd (CPA). The original standards have been in use since 1992 and it was recognised that extensive revision was required. A standards revision group was established by CPA and this group used several international standards as source references, so that the resulting new standards are compatible with the most recent international reference sources.

Rapid responses of British butterflies to opposing forces of climate and habitat change.

Habitat degradation and climate change are thought to be altering the distributions and abundances of animals and plants throughout the world, but their combined impacts have not been assessed for any species assemblage. Here we evaluated changes in the distribution sizes and abundances of 46 species of butterflies that approach their northern climatic range margins in Britain-where changes in climate and habitat are opposing forces. These insects might be expected to have responded positively to climate warming over the past 30 years, yet three-quarters of them declined: negative responses to habitat loss have outweighed positive responses to climate warming.

The role of bioassays in the development, licensing and batch control of biotherapeutics.

The role of bioassays in ensuring the safety and efficacy of medicines produced by biotechnology intended for human use is under continuous review. It is a complex area, in which the rapid scientific and technological advances have been accompanied, more or less synchronously, by novel clinical applications. The need to match the rapidity of these developments with the necessarily more cautious regulatory procedures for licensing and controlling medicines in the pharmaceutical marketplace has produced an area of active debate.

The First International Standard for Somatropin: report of an international collaborative study.

Following an earlier decision to move away from the in vivo bioassay for determination of the potency of therapeutic somatropin (recombinant DNA human growth hormone), 18 laboratories in 12 countries participated in an international collaborative study designed to establish an international standard for somatropin, calibrated both by bioassay and by physicochemical assays of somatropin content. The mean in vivo biological potency of preparation studied, coded 88/624, was 6.75 IU/ampoule (fiducial limits 6.

The role of bioassays in the assessment of recombinant proteins.

Although the need is diminishing, biological assays still have an important place in the characterization and quality control of therapeutic peptides prepared by recombinant DNA technology. This role needs to be assessed on a case-by-case, product-by-product basis. It includes as a minimum the need to establish during product development the range and quantitative nature of its biological activities, particularly those relevant to its intended clinical use and potential side effects.

Analysis of therapeutic growth hormone preparations: report of an interlaboratory collaborative study on growth hormone assay methodologies.

Recombinant DNA-derived human growth hormone (somatotropin) is widely used to treat growth hormone-deficient children. The potency of this product is determined by in-vivo bioassay in hypophysectomized rats, which is imprecise, costly and invasive, and there have been suggestions that it could safely be replaced with in-vitro or physico-chemical alternatives. In this report we present the results of a collaborative study designed to test this proposal.

International Standards for human prolactin: calibration by international collaborative study.

Three ampouled preparations of purified human prolactin were assessed by 20 laboratories in eight countries for their suitability to serve as International Standards for the estimation of human prolactin in serum. Bioassays (pigeon crop sac assays and NB2 cell assays) were carried out in two laboratories, radioreceptor assays by one laboratory and radioimmunoassays by 17 laboratories. By physicochemical analysis the preparations appeared similar.

Three methods compared for estimating the fraction of testosterone and estradiol not bound to sex-hormone-binding globulin.

Here we propose and validate, both theoretically and experimentally, a new technique for measuring the percentage of non-sex-hormone-binding globulin (SHBG) bound to testosterone and estradiol. In this method, SHBG is saturated with 1 mumol of 5 alpha-dihydrotestosterone per liter and the non-protein-bound fraction is subsequently measured in treated and untreated samples by centrifugal ultrafiltration dialysis (CUFD). We compared this technique with two previously published methods for measuring the percentage of albumin-bound steroid--ammonium sulfate precipitation and heat denaturation of SHBG followed by CUFD--and also with previously published computer predictions.

The production and characterisation of monoclonal antibodies against human prolactin and the development of a two-site immunoradiometric assay.

Monoclonal antibodies against human prolactin (PRL) have been produced and characterised and used to develop a sensitive two-site immunoradiometric assay (IRMA). Nine anti-PRL monoclonal antibodies were assessed for reactivity in immunoblotting experiments with PRL, hPL, hGH and pituitary gland extract. There was no detectable crossreactivity with hPL or hGH.