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.

[Alpha fetoprotein in congenital hypothyroidism before and during treatment]. / L'alphafoetoprotéine au cours de l'hypothyroïdie congénitale avant et sous traitement.

BACKGROUND: Screening for congenital hypothyroidism (CH) is an opportunity to investigate maturation by measuring alphafetoprotein (AFP). PATIENTS AND METHODS: Blood AFP was measured in 73 full-term infants (controls), 22 infants with permanent CH and 19 with a transient form (FT) of hypothyroidism. It was also measured in mothers of the two groups with hypothyroidism. AFP was measured by RIA and its value was compared to those of FT4, TSH and bilirubin. RESULTS: Blood AFP was higher in patients with CH with significant differences between patients who had jaundice or not, but AFP was not significantly different in FT patients and controls. Initial values of AFP in both CH and FT population was correlated to the levels of AFP in their mothers. Under treatment with 7.5 micrograms/kg/day of l-T4, AFP levels remained increased at T15, then gradually normalized at T30-T60. The log of AFP was correlated to TSH levels between T15 and T60 but was not correlated to FT4 levels. Preliminary results at one year of age show that IQ seems better in infants with early normalization of AFP. CONCLUSIONS: Prolonged follow-up is necessary to assess the possibility that initial kinetics of AFP under therapy have a prognostic value for estimating the quality of outcome.

[Ultra-sensitive TSH and the TRH test in the follow-up of thyroid and pituitary diseases]. / TSH ultra-sensible et test à la TRH dans le suivi des pathologies thyroïdiennes et hypophysaires.

Basal TSH values measured by an ultra-sensitive method (TSH-US) were compared with the response of TSH under TRH (delta TSH) in 178 patients. In all thyroid pathologies and in patients without thyroid or hypophyseal pathology, results are in good agreement, i.e., delta TSH is proportional to basal TSH-US (r = 0.93). In 92 patients with hypophyseal diseases, no correlation between delta TSH and basal TSH-US could be found.

[Surgery of primary hyperparathyroidism. Contribution of the peroperative assay of urinary cyclic AMP]. / Chirurgie de l'hyperparathyroïdie primaire. Apport du dosage peropératoire de l'AMP cyclique urinaire.

The increase of nephrogenic cyclic AMP is an excellent index of parathyroid hypersecretion. A successful treatment of primary hyperparathyroidism results in a rapid fall in nephrogenic cAMP. In a series of 24 patients with proven primary hyperparathyroidism (hyperplasia 3, adenoma 21) and 2 patients with suspected hyperparathyroidism, the success of surgical excision was evaluated by measuring the urinary cAMP/urinary creatinine ratio (R), which in the absence of renal impairment, is proportional to the level of nephrogenic cAMP. Sequential assays of urinary cAMP and creatinine were performed during surgery; laboratory results were available within less than one hour. Among 22 patients with elevated baseline value or R, R became normal in 18 and decreased by more than 50% in 3; these findings suggested that the operation would be successful. In 1 case, R was not measured as the patient had impaired renal function. In another patient with normal baseline value of R, R did not significantly decrease after excision. Surgery failed in 1 patient, although the high value of R at the end of the operation should have prompted us to continue. Finally, in 2 patients the diagnosis was erroneous since R was lower than 0.5 as in controls. Surgeons, therefore, now have a reliable biochemical method at their disposal, but its use will be limited by its cost and complexity.

Free thyroxine measurement by one-step method in the plasma of treated and untreated hypothyroid infants.

The one-step radioimmunoassay of free thyroxine (f-T4) using a gamma-coated kit was used in this study. In controls the mean plasma levels (pmol/l) were 20.8 (range 13.5-37) during the first days of life, 17.4 (11.5-27) from 1 week to 1 year, and 17.0 (10-24.5) after 1 year. In preterm newborns it was correlated with the length of gestation. Among 23 untreated hypothyroid infants aged 15-22 days, f-T4 was undetectable in those with athyreosis, while in cases with dysgenetic thyroid it was variable, correlated to the width of the gland (r = 0.77, p less than 0.01). In 44 hypothyroid patients treated with l-T4, a highly significant positive correlation was found after the 1st month of treatment between plasma f-T4 and the daily l-T4 dose (r = 0.46, p less than 0.01), and a negative one between f-T4 and plasma TSH (r = -0.59, p less than 0.001). It is concluded that measurement of f-T4 offers a valuable means for control of diagnosis and treatment in congenital hypothyroidism, especially useful for avoiding both under- and overtreatment. Its correlations suggest that it is the most reliable hormonal measurement in the follow-up of thyroid children.

[Direct assay of free thyroxine in children. Application to the monitoring of the treatment of hypothyroidism]. / Dosage direct de la thyroxine libre chez l'enfant. Applications à la surveillance du traitement des hypothyroïdies.

A direct measurement of free thyroxine (FT4) by a radio-immunologic method using an analogue of thyroxine as tracer allowed to establish the normal values in 341 children from birth to puberty. These values were used as reference for the determination of free T4 in the diagnosis and management of treatment for congenital hypothyroidism. In 44 treated hypothyroid children, there was a positive correlation between the serum concentration of free T4 and the amount of levothyroxine given daily (r = 0.46, p less than 0.01). There was also a negative correlation between free T4 and serum TSH (r = 0.59, p less than 0.001). Thus, the measurement of free thyroxine seems to be a more reliable, more accurate and more sensitive parameter than that of total thyroxine or TSH for controlling the treatment of congenital hypothyroidism.

[Blood gastrin levels after electrical stimulation of the vagus (author's transl)]. / Variations de la gastrinémie après stimulations électrique des pneumogastriques.

Acid secretion from the cells bordering the gastric fundus may be stimulated by a direct action of histamine or pentagastrin... or from electrical stimulation of the vagus as used to control vagotomy. It is not known, however, whether this latter effect is due to direct stimulation of the lining cells or follows hypersecretion of gastrin. In order to clarify this point, a stimulus was applied to the isolated vagus during vagotomy, and gastric acid and peripheral blood gastrin levels measured. Increased or decreased gastrin levels were noted in about the same number of cases. No direct relationship with pH variations was observed, and confirmation that vagal stimulation affects the lining cells through the intermediary of increased systemic blood gastrin levels was not obtained.

Falsely elevated serum thyrotropin (TSH) in newborn infants: transfer from mothers to infants of a factor interfering in the TSH radioimmunoassay.

In a TSH screening program for congenital hypothyroidism we detected seven newborn infants with normal plasma T4 and T3 levels but high immunoassayable TSH. Similar findings were obtained in their mothers. Serial plasma dilution curves, with and without the addition of normal rabbit serum to the samples, showed that the result of TSH assay performed with antihuman TSH rabbit antiserum was falsely elevated in mothers and infants by an interfering factor. Follow-up of the infants demonstrated that the falsely elevated plasma TSH levels returned to normal within the first 6 months of life. On the contrary, plasma TSH levels remained high in the mothers. These results suggested a placental transfer of maternal antibodies. Indeed, the analysis of the mothers anamnesis revealed that all had previously received injections of a microbial vaccine cultured on a rabbit lung-containing medium. We conclude that placental transfer of a maternal antirabbit factor may cause an artefactual hyperthyrotropinemia in the newborn and the incorrect diagnosis of neonatal hypothyroidism. This can be avoided by the addition of normal rabbit serum or immunoglobulin to the TSH RIA tubes.

[Problems encountered during intensive routine scale performace of paper T4 and TSH radioimmunoassays (author's transl)]. / Etude critique des problèmes associés à la pratique en grande série des dosages radioimmunologiques de T4 et de TSH sur papier.

High sensitivity attained in radioimmunoassays explains the important role played by specialized laboratories as screening partners for early neonatal hypothyroidism detection. In this paper, the author tries to point out optimal technical conditions to be followed while performing at routine scale T4 and TSH paper immunoassays choice of filter paper, blood collection and storage, assay, quality control, assay mecanization, computer calculation of results).

[Nitroglycerin infusion in patients with or without cardiac failure. Demonstration by multifactorial analysis (analysis of correspondences) of three types of hemodynamic response dependent upon the initial state (author's transl)]. / La trinitrine intraveineuse chez les malades avec et sans insuffisance cardiaque. Mise en évidence par une analyse multifactorielle (analyse des correspondances) de 3 types de réponse hémodynamique dépendant de l'état initial.

The effects of nitroglycerin on systemic vascular resistance and cardiac output are highly debated. This study demonstrates that these effects depend on the initial haemodynamic condition, and explains the conflicting results previously reported. 31 patients presenting initially with a fairly wide spectrum of various haemodynamic parameters underwent cardiac catheterisation with measures of parameters before and after nitroglycerin infusion. Multifactorial statistical analysis by correspondence analysis identifies 3 types of haemodynamic responses and demonstrates the association of each response with a particular haemodynamic profile. It is demonstrated that systemic vascular resistance is decreased only when it is initially elevated and cardiac output is increased only when initial pulmonary wedge pressure and systemic vascular resistance are elevated and cardiac output is low. The effects of nitroglycerin on cardiac output, systemic vascular resistance, heart rate and arterial pressure differ significantly according to the presence or not of cardiac insufficiency and depend mainly on the initial value of three parameters: systemic vascular resistance, pulmonary wedge pressure and cardiac output.

Pharmacokinetic study of ketoprofen (19.583 R.P.) in man using the tritiated compound.

Ketoprofen (19.583 R. P., Profenid N. D., Orudis) labelled with tritium was administered orally to 4 patients (3 men - 1 woman) at a dose of 150 mg (therapeutic dose) with a radioactivity of approximately 500 muCi. Tritiated ketoprofen capsules, which disintegrated in the stomach, were administered in particle size of the same order as in the clinical trial material. The ketoprofen plasma levels and the quantities of the compound excreted in the urine and faeces were measured for 5 days after the administration of the capsules. Ketoprofen is absorbed rapidly and its plasma levels, which vary from patient to patient, can be comparatively high (9 to 21.3 mg/l), but these levels fall rapidly by 2 or 3 half-lives. Ketoprofen and its metabolites are excreted mainly in the urine (approximately 85% of the radioactivity administered is excreted within 5 days) and to a very limited extent in the faeces (within 5 days: approximately 1 to 8% of the radioactivity administered). Thus the evaluation of the radioactivity shows that the compound and its metabolites are almost completely excreted by the 5th day after administration. The ketoprofen urinary excretion rate is fairly closely correlated with the disappearance of the compound from the plasma. Overall measurements of the compound in the plasma and urine show that ketoprofen undergoes a relatively significant degree of metabolic transformation in man since, on an average, approximately 55% of the administered compound is recovered as metabolites from urine samples. In faeces, the relative significance of the transformation into lipo-soluble metabolites and water-soluble substances suggests that the metabolic transformation has a bacterial origin which varies in different individuals. The parameters of the pharmacokinetics of ketoprofen and its metabolism show no differences between the sexes in the cases studied.

[Quantitative functional exploration of the salivary glands. Measurement of salivary elimination of technetium 99]. / L'exploration fonctionnelle quantitative des glandes salivaires Mesure de l'élimination salivaire du technetium 99m

The authors propose a method for the quantitative functional exploration of the salivary glands using two objective criteria, on the one hand the level of fixation in the parotid of technetium 99m injected in the form of its pertechnate and on the other hand by the fraction of radioactivity found in different specimens of saliva collected in the course of a test carried out using a pharmacological agent free of toxic effects--lemon juice. The quantitative results obtained and its simplicity render the method particularly useful in evaluating the course of salivary function in all forms of disorder, pathological or iatrogenic.