Multicenter evaluation of the Elecsys CA 125 II assay.

The technical performance and clinical usefulness of the newly developed Elecsys CA 125 II assay (Boehringer Mannheim) was evaluated in a multicenter study. Imprecision studies were carried out using control sera and human pool sera with CA 125 concentrations from 11 to 1026 U/ml. Within-run CVs between 0.7 to 4.8% (median 1.7%) and between-day CVs between 2.4 to 10.9% (median 5.7%) were found. Method comparison studies with Enzymun-Test CA 125 II carried out in four laboratories yielded slopes between 0.94 to 1.07 and intercepts < 3 U/ml. A good comparability of the Elecsys CA 125 II assay was also found with one MEIA and the Centocor" IRMA. For a second MEIA and a second IRMA the slopes were 1.23 and 1.42, and the corresponding correlation coefficients were 0.987 and 0.977, respectively. The Elecys CA 125 II concentrations are clearly related to the tumor stage of ovarian carcinoma patients. The maximum of diagnostic efficiency of ovarian carcinoma patients compared with patients of benign gynecological diseases is reached at 150 U/ml with a specificity of 93% and a sensitivity of 69%. Follow-up studies of ovarian carcinoma patients reflect the status of the disease and the effect of various therapeutic applications. The technical and clinical evaluation of the Elecsys CA 125 II assay show a superior analytical performance with a broad measuring range up to 5000 U/ml and a short measuring time of 18 minutes.

A new approach for clinical biological assay comparison and standardization: application of principal component analysis to a multicenter study of twenty-one carcinoembryonic antigen immunoassay kits.

BACKGROUND: Principal component analysis (PCA) is a powerful mathematical method able to analyze data sets containing a large number of variables. To our knowledge, this method is applied here for the first time in the field of medical laboratory analysis. METHODS: PCA was used to evaluate the results of a blind comparative study of 21 carcinoembryonic antigen (CEA) reagent kits used to determine CEA concentration in a panel of sera from 80 patients. RESULTS: The mathematical technique first eliminated the variations attributable to the use of different calibrators. The PCA representation then gave a global view of the dispersion of the kits and allowed the identification of a main homogeneous group and of some discrepant kits. CONCLUSIONS: PCA applied to the in vitro diagnostic reagent field could contribute to the standardization process and improve the quality of medical laboratory analyses. A standardization method using a panel of patient sera is proposed.

Analytical and clinical evaluation of an electrochemiluminescence immunoassay for the determination of CA 125.

The CA 125 II assay on the Elecsys(R) 2010 analyzer was evaluated in an international multicenter trial. Imprecision studies yielded within-run CVs of 0.8-3.3% and between-day CVs of 2.4-10.9%; CVs for total imprecision in the manufacturer's laboratory were 2.4-7.8%. The linear range of the assay extended to at least 4500 kilounits/L (three decades). Interference from triglycerides (10.3 mmol/L), bilirubin (850 micromol/L), hemoglobin (1.1 mmol/L), anticoagulants (plasma), and several widely used drugs was undetectable. Method comparisons with five other CA 125 II assays showed good correlation but differences in standardization. A 95th percentile cutoff value of 35 kilounits/L was calculated from values measured in 593 apparently healthy (pre- and postmenopausal) women. In 95% of patients with benign gynecological diseases CA 125 was 190 kilounits/L. A comparison of CA 125 values obtained with the Elecsys test and with other common CA 125 tests in monitored patients being treated for ovarian cancer showed identical patterns. In conclusion, the Elecsys CA 125 II assay is linear over a broad range, yields precise and accurate results, is free from interferences, and compares well with other assays.

Imbalances in serum proinflammatory cytokines and their soluble receptors: a putative role in the progression of idiopathic IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis, and a potential target of immunoglobulin therapy?

Following recent experimental data suggesting an aggravating effect of circulating proinflammatory cytokines on the histological lesions of IgAN, we studied changes in serum proinflammatory cytokines and their soluble receptors and antagonists in patients treated with polyvalent immunoglobulins (15 with severe nephropathy who had indicators of poor prognosis: heavy proteinuria, hypertension, altered renal function and Lee's histological grade III or IV; and 14 with moderate forms of IgAN who had permanent albuminuria > 300 mg/day and < 2000 mg/day, Lee's histological grade II and a glomerular filtration rate > 70 ml/min) in comparison with healthy controls (n = 20) and patients with non-IgA nephritides (n = 50). These were measured by means of specific immunometric assays before and after 9 months of immunoglobulin therapy. Total tumour necrosis factor (TNF) serum and IL-6 levels were elevated in IgAN patients before therapy, relative to controls, and normalized after immunoglobulin therapy. Levels of soluble TNF receptor of type I (sR55) and type II (sR75) increased on immunoglobulin therapy. TNF index alpha-55,75 used to assess biologically available TNF-alpha (ratio of total TNF-alpha divided by levels of soluble TNF receptors sR55 and sR75) was elevated before therapy and was below healthy control values after 9 months of immunoglobulin administration. Levels of serum IL-1 receptor antagonist were low prior to immunoglobulin administration in patients with severe forms of IgAN, and normalized on therapy. Serum interferon-gamma was unmodified. The histological activity index correlated with serum total TNF-alpha, TNF index alpha-55,75 and serum IL-6 levels, whereas proteinuria correlated with serum total TNF-alpha and TNF index alpha-55,75 but not with serum IL-6. These data suggest that the overproduction of proinflammatory cytokine is unbalanced by their natural antagonists in IgAN and Henoch-Schönlein syndrome. This process may play a role in the progression of the disease and be one of the targets of immunoglobulin therapy.

Comparison of six serum ferritin immunoassays and isoferritin spectrotypes in malignancies.

Serum ferritin was measured by six enzyme immunoassays in specimens from patients with digestive cancers (n = 30) and hematologic malignancies (n = 33). Most mean comparisons show significant differences in both groups of patients. In digestive cancers correlations between any two methods are very satisfactory (r > 0.99) but a proportional bias is often observed. In hematologic malignancies, correlations are bad (r < 0.80 in 8 out of 15 correlations) because of many discrepant values. Isoelectric focusing separation of isoferritins was performed in most specimens and the pattern of each serum was compared to the between kit CV. We conclude that an 'acid' spectrotype increases between-kit analytical variability. We try to explain the results taking into account the nature of the immunological systems and the cross-reactions with tissular isoferritins. In conclusion, our results indicate that large differences may be observed in sera from hematologic malignancies (leukemias, lymphomas ... ) We recommend that monitoring be achieved by the same method of measurement.

Reducing unnecessary laboratory use with new test request form: example of tumour markers.

To limit the ordering of serum tumour marker tests that are clinically irrelevant, we designed a new request form. This is a matrix of boxes, rows being individual markers and columns body organs. The box at the intersection of line and column is colour-coded to indicate whether the test is appropriate or not. These ratings were allocated on the basis of published data and local consensus. This new form replaced the form in use at our hospital at the beginning of 1992, and resulted in a 25% decrease in the ordering of tumour markers. Adapting the design of the test request form is a low-cost intervention that combines both economic and clinical requirements in reducing the prescription of tests that are useless in a given clinical situation.

Diurnal variations of acute mountain sickness, colour vision, and plasma cortisol and ACTH at high altitude.

Time dependence of colour vision in the green/red axis, signs of acute mountain sickness (AMS), and plasma cortisol and ACTH concentrations were studied in eight sea-level male natives exposed 79 h to altitude hypoxia at 4,350 m. Colour vision (CV) was explored every 2 h from 08:00 to 20:00 hours by means of two portable anomaloscopes, one derived from Essilor CHROMOTEST and the other from the OSCAR. Significant diurnal variations in CV were found using both anomaloscopes, major alterations in green relative to red sensitivity being seen in the early morning. AMS scores also showed remarkable diurnal variations, parallel to those of plasma cortisol and CV, with maximum values observed at 08:00 hours. Cortisol diurnal rhythm was maintained in hypoxia, with mean concentrations higher than in normoxia. ACTH followed the same trend, but variations were not significant. Significant correlations were found between instant values of CV, cortisol, and AMS score, but no causal relationship between these variables can be ascertained.

[The value of the serum level of the prostate-specific antigen in prostatic pathology]. / Intérêt du dosage sérique de l'antigène spécifique prostatique dans la pathologie prostatique.

Development of serum assays for prostate-specific antigen (PSA) has provided physicians with a new marker for carcinoma of the prostate. PSA was compared to prostate acid phosphatases (PAP), the reference serum marker, in 162 patients including 54 patients with carcinoma of the prostate (CP), 84 patients with benign hypertrophy of the prostate (BHP), and 24 controls free of prostate disorders. PSA appeared more sensitive but less specific than PAP. Results showed that PSA is not suitable for routine screening in the population at large where BHP is common. In BPH, the rise in PSA concentrations parallels the size of the hypertrophy. However, in patients with CP, PSA seems more sensitive than PAP for evaluating tumor spread and response to treatment. The prognostic bearing of increased levels in patients with apparently localized carcinomas remains to be elucidated.

[The coefficient of saturation of iron in transferrin]. / A propos du coefficient de saturation en fer de la transferrine.

Theoretical iron fixation capacity of transferrin (FCT) can be calculated on its immunochemical titration: (FCT (mumol/l = transferrin (g/l) x 25). Today, its reckoning is more advisable to serum total iron binding capacity measurement. The authors studied the effects of this new proceeding upon usual values interval of transferrin saturation (i.e. serum iron/FCT ratio). The mean value and the distribution of transferrin saturation appear displaced with regard to those achieved by chemical measurement of serum total iron binding capacity. We discuss interpretation of transferrin saturation related to its methods of determination and its semiological interest.

[Reevaluation of strategies for the diagnosis of iron deficiencies]. / Réévaluation des stratégies pour le diagnostic des carences martiales.

Serum ferritin has been assayed by two methods. Radio-Immunology and Enzymo-Immunology in two group of young females. Iron deficiency is considered as unequivocal if serum ferritin is lower than 20 micrograms/l whatever the method used analysis of red cell indices in iron deficient females has shown that anemia, hypochromia and microcytosis are very late events and that their sensitivity for the diagnosis if iron deficiency is very poor.