Volume 36, Issue 1

The present article proposes personal suggestions to improve determinations and clinical interpretation of results of lipoprotein(a) assays. Methods and procedures for sampling and quantification of the various isoforms of lipoprotein(a) in serum, plasma and urine are reviewed with the aim of improving the reliability and reproducibility of results and reinforcing the clinical utility of lipoprotein(a) measurements.

The concentration of soluble transferrin receptors in serum has proven to be a reliable predictor of iron status in adults. Its high sensitivity for iron deficiency combined with a small sample size (10 μl) makes it an interesting parameter for the assessment of iron stores in newborn infants. In the present study we investigated the usefulness of the concentration of soluble transferrin receptors in serum in the assessment of iron metabolism in the newborn. Infants born after an uncomplicated labour were compared to infants in the intensive care unit. The concentration of soluble transferrin receptors in serum was found to be elevated compared to normal adults and independently of iron metabolism. The concentration of soluble transferrin receptors did not correlate with serum iron and ferritin concentrations. In contrast to what was found in other studies, no relationship could be demonstrated between soluble transferrin receptors and birth weight or gestational age. The results of this study have shown that care has to be taken in the interpretation of the concentration of soluble transferrin receptors in serum in newborn infants. It seems to be a parameter which is independent of iron metabolism at least during the first days of life.

Currently no available immunoassay system offers complete protection against spuriously elevated or lowered results due to interference by Human Anti-Mouse Antibodies (HAMA). Although routine use of chromatography procedures is not an acceptable option because of the extra cost and workload involved, such a procedure would be highly desirable to ensure accurate immunoassay results. The present report describes a relatively simple affinity chromatography procedure using a HiTrap Protein G column to isolate immunoglobulin G (IgG) HAMA, followed by a HiTrap N-hydroxy-succinimide(NHS)-activated column coupled to goat-anti human immunoglobulin M (IgM) to bind IgM HAMA. To examine the usefulness of this purification procedure we determined CA 125 in forty serum samples prior to and following chromatography. Pre- and post-injection samples were obtained from 20 patients injected with 1 mg of 111In-Iabelled murine OC 125 F(ab′) 2 fragments in an immunoscintigraphy study. It is shown that this analytical procedure provides a technique to determine the extent and the nature of the existing HAMA interference in samples of patients after in vivo use of monoclonal antibodies for diagnostic or therapeutic purposes. The procedure can also contribute to the clarification of clinically discordant CA 125 results. Finally, the availability of such a procedure in the clinical laboratory provides an opportunity to test the robustness of newly developed immunoassay systems towards HAMA interference.

In a prospective, descriptive study in 25 patients with acute pancreatitis neopterin plasma concentrations were found to be associated with the severity of the disease, which was assessed using weights of the worst 17 physiological abnormalities of the APACHE-III score over a 24 h period after hospital admission. Neopterin concentrations were higher in severe pancreatitis (n = 10) compared to mild disease, and there existed a positive exponential correlation between neopterin and the Acute Physiology Score (r = 0.66). Higher neopterin concentrations were associated with the development of multiple organ failure (p = 0.012) and death (p = 0.019). At a cut-off concentration of 12 nmol/l the sensitivity (80 %) and specificity (100 %) of neopterin for the discrimination between mild and severe clinical course of pancreatitis was more accurate than C-reactive protein at a risk threshold of 1.2 g/l (70 % and 87 %). Development of pancreatic necrosis was associated with higher neopterin concentrations than edematous pancreatitis (p < 0.001).

The main objective of the Stanislas cohort is to study the role and the contribution of genetic and environmental factors to cardiovascular status. We plan: a) to describe the degree of association of a large number of cardiovascular risk indicators with cardiovascular endpoints, b) to evaluate the contribution of genetic and that of environmental factors to this association, c) to follow the evolution of these risk indicators during a period of at least ten years, d) to search for the determinants influencing this evolution. The principal variables studied are: a) to describe the degree of association of a large number of cardiovascular risk indicators with cardiovascular endpoints, b) to evaluate the contribution of genetic and that of environmental factors to this association, c) to follow the evolution of these risk indicators during a period of at least ten years, d) to search for the determinants influencing this evolution. a) blood pressure, cardiac mass, and wall thickness of carotid and femoral arteries, b) obesity and fat mass, c) indicators of lipid metabolism, d) genetic polymorphisms of several cardiovascular risk candidate genes, e) food, tobacco and alcohol consumption, f) consumption of drugs and anti-oxidant vitamins. Between September 1993 and August 1995, 1006 families consisting of the two biological parents with at least two children were recruited totalling 4295 individuals. This cohort will be followed up until 2004. There will be two health examinations five and ten years after the initial examination. A bank of blood samples (serum and plasma) in liquid nitrogen and DNA (−80 °C) has been established.

We evaluated the performance of an enzymatic method using dry chemistry for serum total carbon dioxide (tCO 2 ) determination using a Vitros 500 analyser. Imprecision results were acceptable and the linearity was verified for concentrations within a range of 5.5–39.2 mmol/l, i.e. y measured = 0.93 x calculated +1.32, r = 0.99. The Vitros tCO 2 method was unaffected by haemoglobin at all concentrations tested. Significant interference was caused by bilirubin at concentrations higher than 30 μmol/l; the addition of bilirubin lowered the apparent values for tCO 2 dose-dependently. Serum tCO 2 results were practically the same as those for plasma. The reference interval for venous tCO 2 concentrations in a healthy population was: 22.4–34.2 mmol/l (mean: 28.3 mmol/l). Comparison of venous serum tCO 2 results assayed using the Vitros method with bicarbonate (HCO 3 − ) values calculated by blood gas determination of pCO 2 and pH in arterial blood samples gave poor agreement, r = 0.58. The data revealed a mean difference of 5.48 ± 3.09 mmol/l between the tCO 2 measurements and calculated bicarbonate. This was statistically (p = 0.01) and clinically significant. We conclude that the Vitros method provides reliable tCO 2 results in venous serum but this method must not be used as an interchangeable alternative to calculated arterial bicarbonate in order to avoid confusion, misinterpretation of results and erroneous therapeutic decisions.

The performance and practicability of 2 blood glucose meters (Glucocard Memory 2 and Accutrendr sensor) were evaluated. Both glucose meters produced acceptably precise results in the hyper- and normoglycaemic concentration ranges. In the hypoglycaemic concentration range, the imprecision of Accutrend ® sensor was much higher than recommended by the American Diabetes Association. Within-run coefficients of variation for Glucocard Memory 2 were 6.3 %, 3.9 % and 2.4 % at glucose concentrations of 1.7 mmol/l, 5.8 mmol/l and 11.7 mmol/l, respectively; for Accutrend ® sensor these were 15.2 %, 5.0 % and 1.2% at respective concentrations of 0.9 mmol/l, 4.2 mmol/l and 19.6 mmol/l. Between-day coefficients of variation for Glucocard Memory 2 were 4.8 % and 3.5 % at glucose concentrations of 3.9 mmol/l and 17.2 mmol/l, respectively and for Accutrend ® sensor they were 3.8 % and 2.9 % at glucose concentrations of 3.8 mmol/land 18.7 mmol/l, respectively. Results were linear over a range of 1.6 mmol/l–29.7 mmol/l for Glucocard Memory 2 and 1.6 mmol/l–33.3 mmol/l for Accutrend ® sensor. Results of both blood glucose meters correlated closely with the hexokinase/glucose-6-phosphate dehydrogenase laboratory method. Ninety-eight percent of both Glucocard Memory 2 and Accutrend ® sensor results were within 20 % of the comparison method values. Ninety-three percent of the Glucocard Memory 2 and 96 % of the Accutrend ® sensor results were within 15 % of the comparison method results. An inverse relation between the glucose readings and haematocrit values was observed for both blood glucose meters in the hyperglycaemic range and this effect was more pronounced for Accutrend r sensor. In the normo- and hypoglycaemic ranges the effect was insignificant and absent, respectively. Minimum sample volume for Glucocard Memory 2 was 3 μl and for Accutrend ® sensor it was 9 μl. Lower sample volumes gave erroneous results. Presenting more than the required volume had no effect on results.

We evaluated circulating aminoterminal and carboxyterminal propeptides of type I procollagen and total alkaline phosphatase levels in eighty consecutive patients affected by Paget's disease of bone. We compared the biochemical data with the extent of bone disease calculated on the basis of the bone scintigraphic indices. Serum aminoterminal propeptide of type I procollagen levels were high in 77% of patients, serum carboxyterminal propeptide of type I procollagen levels in 22% and serum total alkaline phosphatase levels in 76%. We found significant correlations between the three markers studied. The three biochemical markers correlated significantly with the bone scintigraphic activity indices, but the highest correlation coefficient was between the aminoterminal propeptide and total alkaline phosphatase. We conclude that there is a discrepancy between serum levels of the propeptides studied in relation to Paget's disease of bone. The sensitivity of the carboxyterminal propeptide of type I procollagen in this disease is low. In contrast the aminoterminal propeptide may be as sensitive a marker for the evaluation of this disorder as total alkaline phosphatase, and in addition may be more specific.

Historical research on the concept of normality, its roots and its development show that this concept has its sources in very different areas of scientific and medical thinking. Of great importance were: (i) a new theory of disease arising early in the 19th century supposing a continuous change from the healthy to the diseased state; (ii) the examination of variation within and between species of plants and animals; (iii) the clinical theory of constitution developed to describe the wholeness of the individual determined both by genetic factors and the influence of the environment; (iv) the development of mathematical and statistical tools starting with the adaptation of Bernoulli's “law of the great numbers” and Gauss' and Legendre's “law of errors” to biological measurements by the Belgian astronomer Quetelet. At the end of the First World War the concept of normality was first discussed. An idealistic “value norm” was set against a statistical “frequency norm”. Between 1920 and 1930 the principles of our present concept were accepted and the mathematical tools developed. It took several decades to introduce this concept into practical medicine finally being recommended by the IFCC.