"STUDIES ON HYSTERIA"; A METHODOLOGICAL EVALUATION.
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C-Type natriuretic peptide (CNP) is a member of the family of natriuretic peptides with vasodilatory properties, and is produced and secreted by endothelial cells. It seems to play a central role in the paracrine vasomotor control of tone and to be important in several clinical conditions characterized by endothelial dysfunction. We evaluated the analytical performance of a commercially available radioimmunoassay for CNP after a preliminary extraction with Sep-Pak C18. Its analytical reliability was checked by determination of CNP plasma levels in healthy subjects (n = 23) and in patients with different diseases, likely characterized by endothelial dysfunction, such as chronic heart failure (n = 133) and cirrhosis (n = 84). The extraction yield was 78+/-3%. Accuracy of the radiommunological determination was evaluated by dilution (45-370 microL of extracted plasma) and recovery tests (>80%). Between- and within-assay variabilities were < or = 10% and analytical sensitivity was 0.41+/-0.015 pg/tube. Plasma CNP in patients with chronic heart failure and with cirrhosis was significantly raised compared to controls (p<0.0001 and p = 0.001, respectively). The sensitivity, accuracy and variability levels of the method proposed for CNP assay was suitable for reliable detection of changes in CNP plasma levels in the clinical setting.
The empirical evidence concerning the relationship between blood pressure and anthropometric characteristics (triceps skinfold, adiposity, and arm circumference) was assessed by means of meta-analysis. Different studies were evaluated critically for strength of design, methods and associations. It was found that the association between blood pressure and triceps skinfold holds for three different demographic categories. The question as to the independence of these associations remained unsolved. The effect of arm adiposity on the measurement of blood pressure was also discussed. Recommendations are give in order to standardize blood pressure measurements in clinical and research settings.
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OBJECTIVE: To evaluate the feasibility of intrapartum fetal pulse oximetry, the distribution of fetal oxygen saturation values, and the relation with the neonatal outcome in a population with an abnormal fetal heart rate (FHR). STUDY DESIGN: A prospective multicenter observational study, from June 1994 to November 1995. Fetal oxygen saturation was continuously recorded using a Nellcor N-400 fetal pulse oximeter in case of abnormal FHR during labor. Simultaneous readings of fetal oxygen saturation and of fetal blood analysis (FBA) were obtained at inclusion and before birth. Feasibility, adverse effects, distribution of fetal oxygen saturation values and relation with neonatal outcome were assessed. RESULTS: 74 patients were included. From 172 attempted sensor placements, the procedure was impossible in three cases and fetal oxygen saturation values were obtained in 164 cases (95.3%). Physicians considered sensor placement an easier task than FBA attempt (easy in 87.5% vs 78.9% for FBA, p = 0.03). The mean reliable signal time (+/- SD) was 64.7 +/- 32% during the first stage. There were no serious adverse effects in the study population. The mean fetal oxygen saturation during the first stage of labor was 42.2 +/- 8.0% (10th-90th centile range: 30-53%). Fetal oxygen saturation was significantly correlated with scalp pH (r = 0.29; p = 0.01) but not with neonatal umbilical artery pH or gas values. There was a significant association between a low fetal oxygen saturation (< 30%) and a poor neonatal condition. CONCLUSION: The feasibility of fetal pulse oximetry is satisfactory in clinical practice. It is easy to use and provides a fair rate of recorded values, even in a population with suspicion of fetal distress. A low fetal oxygen saturation is significantly associated with an abnormal neonatal outcome.
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The value of soluble transferrin receptor (sTfR) detected in serum is closely related to erythroid TfR turnover rate. An increased erythropoietic activity causes an increase in the sTfR level. Therefore, it is a useful test for monitoring the erythropoiesis. In this study, a new immunoturbidimetric method for automated measurement of sTfR was evaluated for its performance characteristics. Imprecision studies on patients' sera with 1.01 mg/l and 2.94 mg/l concentrations yielded within-run CVs of 1.16% and 1.27%. Accuracy analysis of the test by using the low and high control kit sera with 1.45 mg/l and 5.41 mg/l concentrations were 89.06% and 95.41%, respectively. The evaluation was also performed in 60 individual pediatric subjects, 30 beta-thalassemia/HbE and 30 control pediatric subjects. There is a statistically significant difference of sTfR between both groups (p < 0.0005, 95% Cl = 9.457-14.124). Ninety-five percent of matched pediatric subjects had sTfR level < or = 2.670 mg/l and 93.33% of patients diagnosed beta-thalassemia/HbE had values > 2.670 mg/l. In conclusion, this immunoturbidimeteric test yields good laboratory performance characteristics in terms of precision and accuracy.
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The analytical performance of the automated Enzymun Test System ES 300 and ES 600 (developed by Boehringer Mannheim) for the assay of the tumour markers CEA, CA 19-9, CA 125, and CA 15-3, was assessed from data collected in a multicentre collaborative study in which eleven laboratories were involved. Results of the 1990 cycle of the external quality assessment (EQA) scheme for tumour markers, supported by the Italian National Research Council (CNR), were also used in this evaluation. The within-assay and between-assay precision was found to be 2.0 and 4.3 CV% for CEA, 2.9 and 6.8 CV% for CA 19-9, 3.6 and 9.4 CV% for CA 125, 2.9 and 6.0 CV% for CA 15-3. The between-lab variability of the four tumour markers on ES 300 and ES 600 systems was 9.4, 10.6, 11.9, 9.2 CV% for CEA, CA 19-9, CA 125 and CA 15-3 respectively. These values were comparable to or better than those obtained with the most precise manual kits used by laboratories participating in the 1990 EQA cycle. The agreement between the results from the Enzymun Test and those obtained using other method/kits was evaluated by assaying control samples previously circulated either in the CNR EQA or in the German EQA. The regression analysis indicates that for CEA, CA 125 and CA 15-3 assays the results produced by ES 300 and ES 600 are in good agreement with the consensus means of the EQAs; CA 19-9 results exhibit a worse correlation and are generally lower than the consensus mean. The linearity of the assays for the four tumour markers was checked by dilution tests performed by participants in the collaborative study; in all cases the dilution of the sample did not affect the values obtained.
BACKGROUND: The evaluation of big-endothelin (ET)-1 plasmatic concentrations may serve as another noninvasive marker in patients with cardiovascular diseases, based on the assumption that it may reflect endothelin overproduction more accurately than circulating ET-1. For this reason the analytical performance of an immunoenzimatic assay for plasma Big-ET-1, with or without a preliminary step of extraction, was evaluated. METHODS AND RESULTS: Sensitivity for direct assay was 0.15+/-0.010 fmol/ml (n=27), inter-assay variability, evaluated at 2 different concentrations, resulted 2.5+/-0.062, CV%=5.6 (n=5) and 1.47+/-0.09 fmol/ml, CV%=12.8 (n=4), respectively, while intra-assay variability was 0.89+/-0.022 fmol/ml, CV%=5.6. Sensitivity for the assay with extraction resulted 0.71+/-0.104 (n=6) fmol/ml and intra-assay variability was 3.6+/-0.13 fmol/ml, CV=7.4% (n=4). The comparison between the 2 procedures, performed on 107 plasma samples at different peptide concentrations, showed a close agreement between the results of the 2 procedures for Big-ET-1 values higher than 1 fmol/ml. CONCLUSION: The main limitation of the direct assay is due to possible interference effects while the correct evaluation of extraction yield of the individual samples is the main drawback of the procedure with extraction. These effects become important when assaying samples with low levels of analyte. The direct assay of plasma Big-ET-1, easier to perform, more rapid and less expensive, could be the choice method.
We have studied the relation between the structure and the multidrug resistance-reversal activity of a set of diverse chemicals with the MULTICASE structure-activity program. A number of key structural features were identified as being related to multidrug resistance reversal activity. Using these key features, we identified seven new compounds predicted to have substantial activity. These were obtained and tested experimentally on a CHO/CHRC5 cell line derived from the AB1 Chinese hamster ovary line in the presence of vincristine and vinblastine. Of the seven compounds tested so far, four showed substantial reversal activity, the most potent of them exhibiting activity at par with verapamil.
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The validity of the Carlens Vitagram Index was tested by using the result of therapy in 48 patients with bronchial carcinoma in advanced disease, 54 patients with localized disease and 34 deceased treated surgically. The Carlens Vitagram Index, which is additional and composed of six items, was correlated to a set of additive indexes including the same items but other item weights, which were chosen with non-controversial pre-specified restrictions. The lowest correlation achieved was an indicator of the lowest degree of consistency that could be attributed to the Carlens Index given. The definition of the index was operationalized so far that each item in the set of six items included in the index was regarded as valid, and it was also considered reasonable that only these six items should be included; that each item had a weight; that the index was obtained as a product (weight x item value) sum and that the pre-specified conditions were accepted. By using restrictive conditions the lowest correlation between the index giving the lowest correlation and the Carlens Index for the 48 patients with localized disease was 0.98, for the 54 patients with localized disease 0.91 and for the surgically treated ones 0.83. In addition to the total index, the average index per month was also studied and the corresponding correlations were 0.96, 0.86 and 0.81 respectively. The Carlens Index and its application per month was found to have good validity for inoperable patients and acceptable validity for surgically treated patients. The Carlens Index was shown to be robust and there is reason to believe that it lies close to the optimal index.
The validity of the Carlens Vitagram Index for measuring the quality of survival in bronchial carcinoma was further tested on the basis of the result of therapy in 48 patients with advanced disease, 54 patients with localized disease and 34 deceased patients surgically. Different approaches for index construction are discussed and the "MaxMin" correlation method, in which the highest of the lowest correlations is sought, is presented. The principal algorithms of the method are given, and the mathematical proof and the procedures are described and exemplified. By finding the "MaxMin" correlation a new index was constructed with weights of 20, 12.36, 12.36, 8.18, -6.15 and 0 points. The corresponding weights of the Carlens index are 20, 16, 12, 8, -4 and -2 points. Thus the Carlens index lies very close to the optimal index found with the "MaxMin" method. This result gives further proof that the Carlens index is valid for use in the types of bronchial carcinoma described above.