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C M Sturgeon

Publications and source records attributed to C M Sturgeon.

At least 19 recordsLinked to original sources

Standardization of FSH, LH and hCG--current position and future prospects.

Gonadotropin measurements contribute significantly to patient management in both endocrinology and oncology. Differences in calibration, antibody specificities and assay design mean that gonadotropin results obtained in different methods are still not comparable. Comparing patient results obtained in different methods therefore remains problematic, whether for individual patient care, when assessing the results of multicentre clinical trials, or when formulating national and international guidelines and recommendations. Achieving improved comparability of results for these important analytes will require clear descriptive nomenclature, accurate calibration with highly purified standards, careful characterization of what gonadotropin isoforms methods are measuring, broad recommendations about the most clinically appropriate antibody combinations, and increased awareness of clinically relevant interferences and the action required to minimise their effect. Encouraging manufacturers to standardize and carefully describe the evaluation methods they use, such that data from different manufacturers can readily be compared, is also a pre-requisite for future progress.

Antibody Specificity↗

Tumor markers in the laboratory: closing the guideline-practice gap.

Increasing interest in the use of tumor markers in the clinical management of cancer patients has encouraged development of guidelines by local, national and international groups. Such guidelines generally include recommendations about which markers are likely to be most helpful in given circumstances. Particular requirements and pitfalls in the preanalytical, analytical and postanalytical phases are highlighted. Establishing whether such guidelines are followed in routine practice is difficult, but some indication can be obtained through carefully designed local and national audit projects. Surveys through external quality assessment (proficiency testing) schemes provide a unique means of assessing practice and confirming trends. Such surveys suggest that although increasing numbers of laboratories in the United Kingdom now measure tumor markers, the quality of the service provided over the last ten years has been maintained or improved. While much has already been accomplished, further narrowing of the gap between theory and practice remains a challenge.

Biomarkers, Tumor↗

Acute-phase protein response, survival and tumour recurrence in patients with colorectal cancer.

INTRODUCTION: An acute-phase protein response (APPR) has been associated with reduced crude survival rates and increased recurrence following apparently curative resection in patients with colorectal cancer. This study investigated the prognostic significance of a preoperative and postoperative APPR in relation to disease-specific mortality rate. METHODS: Some 202 patients with colorectal cancer were followed for at least 5 years. C-reactive protein concentration, measured before and at 3 months after operation, was used as an index of the APPR. Univariate and multivariate analyses were performed on a number of potential prognostic factors. RESULTS: Thirty-six per cent of patients had an APPR and this was associated with a higher rate of local tumour invasion, fewer curative resections and a higher carcinoembryonic antigen (CEA) concentration. There was no difference in Dukes' stage between patients with or without an APPR. The most important prognostic factor related to both disease-specific and crude survival was Duke's stage (P < 0.0001). Subgroup analysis demonstrated that APPR had prognostic significance only in patients with advanced disease (P = 0.013). An APPR was present in a minority of patients (11 per cent) after operation and was not associated with increased likelihood of tumour recurrence. CONCLUSION: The APPR is increased in more than a third of patients presenting with colorectal cancer and is associated with more frequent local tumour invasion, fewer curative resections and a higher CEA level. An APPR at 3 months after operation does not have the prognostic significance reported by earlier studies.

Acute-Phase Reaction↗

Analysis of hCG: clinical applications and assay requirements.

Study of the glycoprotein hormones, including hCG, is complex and evolving, and has benefited from recent major advances in analytical technology and molecular biology. It is important to be aware of the effect that these technological advances have, both on the analytical and the clinical requirements for provision of a diagnostic service for hCG. Some aspects of particular relevance are summarized in Table 10.

Biomarkers, Tumor↗

Why do immunoassays for tumour markers give differing results?--a view from the UK National External Quality Assessment Schemes.

External Quality Assessment schemes can provide unique insight into how current methods are performing in the field. Results from the UK National External Quality Assessment Schemes, which monitor performance of immunoassays for a number of tumour markers and peptide hormones in serum, show that in spite of considerable improvements resulting from increased assay automation, major discrepancies in results obtained are still observed. Reasons for this include poor calibration, use of antibodies of differing specificity, and vulnerability to clinically relevant interferences. Variation in quoted reference ranges is also a cause of concern. Each of these important aspects of performance will require attention if improved between-method and between-laboratory agreement is to be achieved.

Antibody Specificity↗

Serological markers for metastatic breast cancer.

Three serum markers, TPS, CA 15.3 and CEA, were used to monitor the response to treatment of 20 patients with metastatic breast cancer. At the time of the first evidence of metastases or at the time of progression of known metastatic disease, 84% of TPS values were above the reference limit, as compared to 74% for CA 15.3 and 84% for CEA. If the treatment instituted was effective, 60% of TPS values showed an early (within 2 or 3 weeks after commencement or change of therapy) reduction in level against only 27% of CA 15.3 and 27% of CEA levels. This suggests that TPS provides a more sensitive and earlier predictor of therapeutic response. In patients with clinical evidence of further progression of disease while on therapy, 86% of TPS values showed persistent elevation or increase, as compared to 71% of CA 15.3 levels and only 36% of CEA levels. It was also noted in these patients that TPS values rose earlier than either CA 15.3 or CEA. This indicates that TPS is a more reliable predictor of response to treatment than the other two markers. In addition, we found that, at the time of presentation, in women who had visceral metastases (liver, lung, or brain alone or in combination), 87% of TPS values were raised, as compared to 80% of CA 15.3 and 73% of CEA values. In women who had bone and soft tissue metastases at presentation, 75% of TPS values were elevated, against 50% of CA 15.3 and 75% of CEA values.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Tumor-Associated, Carbohydrate↗

Validation of target values in external quality assessment schemes for peptide hormones and tumour markers.

Consensus means are tacitly assumed to provide correct target values in many external quality assessment schemes EQAS for peptide hormones and tumour markers. We suggest, however, that such targets should not be used without some evidence of their validity. Comparison of the expected and found increments in the target value on adding known quantities of International Standards to serum pools can provide confirmation of the correctness of target values or, in some cases, identify clearly incorrect targets. Validation of targets is important if EQAS are to stimulate use of correctly calibrated assays, rather than those that simply agree with the most commonly used method(s).

Biomarkers, Tumor↗

Effect of bowel cleansing and colonoscopy on serum CEA levels.

A group of patients being investigated for various forms of colonic pathology showed an apparent rise in serum carcinoembryonic antigen (CEA) level following bowel cleansing at the time of colonoscopy, as compared with the 'resting' level. The rise was particularly marked in a small group of patients with colonic polyps or previous colonic resection for carcinoma, suggesting a need for careful timing in the taking of blood samples. The findings may also have diagnostic importance in identification of patients at higher risk of malignant disease of the colon.

Adult↗

External quality assessment of immunoassays of peptide hormones and tumour markers: principles and practice.

External quality assessment schemes (EQAS) have traditionally emphasised the achievement of between-laboratory consensus. Although this is important, the application of EQAS to relatively new and evolving techniques such as immunoassay calls for a wider and more searching remit if the goals of accurate assays, properly used, are to be achieved. This article outlines the principles of EQAS for peptide hormones and tumour markers, emphasising key aspects such as validation of target values, dependency of results on sample type, and assessment of method characteristics such as vulnerability to interfering factors. The latter are considered to be important as they can affect patient care more seriously than modest degrees of imprecision or inaccuracy. EQAS play a unique role in providing objective data on assays performed in many laboratories under routine conditions and the data they provide can guide improvement in diagnostic reagents and laboratory practice.

Artifacts↗

Carcinoembryonic antigen as a prognostic indicator in the radiotherapeutic management of rectal cancer.

Carcinoembryonic antigen (CEA) levels have been assessed retrospectively in a group of 32 patients with inoperable or recurrent carcinoma of the rectum treated with radiotherapy. Complete clinical regression of pelvic disease was only achieved in patients with pre-treatment CEA levels less than 30 ng/ml when no metastases were present. Pre-treatment CEA assay has a place as a prognostic indicator in the radiotherapeutic management of inoperable or recurrent carcinoma of the rectum.

Carcinoembryonic Antigen↗

Comparison of radioimmunoassay and immunoradiometric assay for serum prostatic acid phosphatase.

We have compared the laboratory performance of immunoradiometric (IRMA) and radioimmunoassay (RIA) methods developed in this laboratory for measurement of serum prostatic acid phosphatase (PAP). The IRMA utilizes a radiolabelled mouse monoclonal anti-PAP and a solid phased rabbit polyclonal anti-PAP. The same rabbit antibody is used in the RIA. The IRMA shows excellent precision over a much wider working range (0.25-1000 micrograms/l) than the RIA (0.73-14.0 micrograms/l), and can be completed in 5 h, while the RIA requires 3 days. Levels in healthy males and in patients with benign prostatic hypertrophy are similar in both assays, upper limits of normal being 1.8 micrograms/l (IRMA) and 4.7 micrograms/l (RIA). The two assay methods correlate very well (r = 0.97) when PAP is measured in serum from prostatic cancer patients, although IRMA results are generally lower than those obtained by RIA. About 20% of patients with non-metastatic prostatic carcinoma had elevated serum PAP, whereas about 80% of those with metastatic disease had raised levels. The diagnostic efficiencies of the RIA and IRMA appeared similar. The value of the IRMA in follow-up and staging remains to be determined.

Alkaline Phosphatase↗

The preparation, characterization and application of monoclonal antibodies to human prostatic acid phosphatase (PAP).

Hybridoma cells secreting anti-PAP were produced by fusion of NS-1 myeloma cells with spleen cells from immunized Balb/c mice. Three of 32 hybrids secreted antibodies. Dilution cloning of the two hybrids producing the highest antibody titres showed that each antibody was monoclonal. One clone from each hybrid (clones ES2 and ES8) was selected for further study. The specificity of the antibodies appeared satisfactory, no inhibition of 125I-PAP binding to antibody being seen with extracts of bone, intestine, kidney, leucocytes, liver or lung. The association constants of the antibodies from ES2 and ES8 were 1.7 X 10(8) and 1.7 X 10(9) l/mol respectively, both were of the IgG1 class. For the immunoradiometric (IRMA) assay of serum PAP 125I-labelled monoclonal antibody was incubated with serum and the PAP-labelled antibody complex was separated by addition of solid-coupled polyclonal anti-PAP. The wide working range of the response curve (0.3-400 micrograms/l) and the rapid analysis time (4 h) offer practical advantages over RIA procedures. Clinical evaluation of the assay is in progress. ES8 antibody also appears to have good specificity for immunocytochemical applications. Localisation of micrometastases in bone in prostatic carcinoma was readily achieved.

Acid Phosphatase↗

Comparison of Bolton-Hunter and chloramine-T techniques for the radioiodination of prostatic acid phosphatase.

A double antibody, semi-automated radioimmunoassay for serum prostatic acid phosphatase (PAP) is described, which uses the 125I-labelled N-succinimidyl-3-(4-hydroxyphenyl) propionate ester of PAP. This type of label has substantially higher immunoreactivity than that prepared using the chloramine-T method of radioiodination. Chromatographic purification of either label on Ultrogel ACA44 further improved immunoreactivity. The lowest detection limit (0 . 35 micrograms/l) was achieved with the chromatographically purified ester label.

Acid Phosphatase↗

Affinity chromatography of sialoglycoproteins, utilising the interaction of serotonin with n-acetylneuraminic acid and its derivatives.

Serotonin, immobilised on Sepharose 4B, has been used to study the affinity chromatography of neuraminic acid and its derivatives. Free N-acetylneuraminic acid and oligosaccharides, polysaccharides, and glycoproteins containing that sugar are specifically bound to the columns. Removal of neuraminic acid from sialoglycoconjugates, or modification of the neuraminic acid residues by periodate oxidation, abolishes their ability to bind to the ligand. The presence of the N-acetyl group, but not the N-glycolyl group, and the integrity of the side chain (C-7-C-9) of the neuraminic acid are essential for binding to serotonin.

Acid Phosphatase↗