Volume 37, Issue 10

We have reviewed the biomedical literature published over the last 25 years in order to try to establish which of four frequently evaluated laboratory parameters ( i.e. serum, or plasma, NSE, LDH, sodium or albumin) might, alone or in combination, give the "best" pretreatment prognostic information in small-cell lung cancer (SCLC) patients, independent of the usual radiological and clinical parameters. From the 45 studies included in this review, the only clear conclusion that can be derived is that it has not yet been clearly demonstrated that the "new" tests (NSE or other tumor markers) are superior to the "old" tests (LDH, sodium, albumin etc.). From the only seven studies that used the same powerful statistical methodologies (Cox's models in association with recursive partitioning and amalgamation proceduce (RECPAM) analysis) it could be concluded that LDH and albumin might have independent prognostic significance in SCLC and in advanced SCLC respectively. Provided that, in the future, both laboratory and statistical expertises are clearly guaranteed in the primary studies in this field, it might become possible to propose laboratory parameters as additional staging parameters in SCLC.

The oxidative hypothesis of atherosclerosis classically implies a central role for low density lipoprotein (LDL) oxidation. However, new antiatherogenic properties have been recognized for high density lipoproteins (HDL), apart from their ability to reverse cholesterol transport. Indeed, native HDL could protect LDL from oxidation, thereby minimizing the deleterious consequences of this process. Several mechanisms have been suggested to explain this protective role. Two HDL-associated enzymes, paraoxonase and PAF-acetylhydrolase, detoxify oxidized phospholipids produced by lipid peroxidation. In addition, HDL could reduce hydroperoxides to their corresponding hydroxides. It has also been suggested that HDL could inhibit oxidized LDL-induced transduction signals. However, in vivo HDL oxidation in the subendothelial space would favor the atherosclerotic process. Indeed, atherogenic properties of these oxidized HDL partly result from some loss of their cholesterol effluxing capacity and from an inactivation of the lecithin-cholesterol acyltransferase, which is a HDL-associated enzyme involved in reverse cholesterol transport. Finally, oxidized HDL could induce cholesterol accumulation in macrophages. Further in-depth investigation is needed to assess these antagonistic effects and their consequences for the atherosclerotic process.

The International Federation of Clinical Chemistry and Laboratory Medicine Working Group for the Standardization of Lipoprotein(a) Assays has initiated a project to select a secondary reference material for lipoprotein( a) that can standardize the measurement of this lipoprotein. Most of the analytical problems with lipoprotein( a) assays are due to apolipoprotein(a) kringle 4 type 2 reactive antibodies and values being expressed in mg/l mass units rather than as nmol/l of apolipoprotein( a) particles. In Phase 2, four manufactured materials were compared for analytical performance, commutability properties and method harmonization in 27 lipoprotein(a) test systems. Results of precision and linearity testing were comparable for all materials whereas testing for the harmonization effect resulted in an among-assay coefficient of variation for corrected lipoprotein(a) values of between 11% and 22%. The material that gave maximum harmonization achieved a variation of < 8% for 18 immunonephelometric and immunoturbidimetric assay systems. It can be hypothesized that this residual variation in part takes into account the inaccuracy of lipoprotein(a) measurement due to apolipoprotein(a) size polymorphism. On the basis of acceptable analytical performance, maximal harmonization effect and documented stability, a lyophilized material has been selected as the common calibrator for lipoprotein(a) to be used in a value transfer procedure by diagnostic companies.

We have investigated the serum level of stem cell factor (SCF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) in relation to a control group and commonly accepted tumour markers, such as carcinoembryonic antigen (CEA) and cytokeratin fragment 19 (CYFRA 21-1). Additionally, we have defined the diagnostic sensitivity, specificity, positive predictive value, negative predictive value and receiver-operating characteristics (ROC) curve of SCF and GM-CSF in non-small-cell lung cancer (NSCLC). The serum levels of cytokines were measured in 50 patients with NSCLC and in 20 healthy subjects. SCF and GM-CSF were determined using enzyme-linked immunosorbent assay (ELISA), CYFRA 21-1 was measured by radioimmunoassay and CEA by microparticle enzyme immunoassay. There were significant increases in circulating SCF and GM-CSF in the lung cancer patients compared to the control group. The diagnostic sensitivity of GM-CSF was higher (70 %) than the sensitivity of CEA (62 %) and CYFRA 21-1 (51 %). The diagnostic specificity of GM-CSF was lower (65 %) than SCF specificity (70 %), but the GM-CSF predictive values were higher in relation to the predictive values of SCF. These results suggest a potential role of SCF and GM-CSF as tumour markers for NSCLC.

Most studies of the relation between psychological performance in the elderly and deficiencies of cobalamin and folate have used methods that determine the blood concentrations of these vitamins, which might not reflect the vitamin status in the tissues. Recently, two new markers, plasma homocysteine and methylmalonic acid, have attracted growing interest since they are considered to reflect the status of cobalamins and folates in the tissues. In a previous study, we noted a strong association between five parameters of well-being and lower concentrations of plasma homocysteine. In the present study, we have extended these observations by determination of plasma methylmalonic acid in the same healthy elderly population. In the present study, 18 out of 100 subjects had increased plasma methylmalonic acid and in 7 of these subjects, the concentrations of serum cobalamin, blood folate, plasma homocysteine and serum creatinine were within normal limits. The relation between plasma methylmalonic acid concentrations and concentrations of serum cobalamin and blood folates and five parameters of well-being were investigated. Concentrations of plasma methylmalonic acid were only weakly associated with the concentrations of serum cobalamin and lower scores on the logical reasoning test. The present study clearly shows that the levels of plasma methylmalonic acid show a much lesser association with the parameters of well-being than did plasma homocysteine.

Coronary heart disease is the most severe form of disease caused by atherosclerosis; and there is a strong relationship between serum lipid concentrations and atherosclerosis. By decade of life, means, standard deviations and selected percentiles were calculated according to sex for serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride in 69,563 Koreans. The prevalence of dyslipoproteinemias which were related to high risk of coronary heart disease were assessed. The mean concentrations of serum total cholesterol and LDL-C in the Korean population were 5.02 mmol/l and 3.00 mmol/l. The 75th and 90th percentile concentrations of total cholesterol were 5.59 mmol/l and 6.24 mmol/l. The mean concentrations of serum triglyceride and HDL-C were 1.58 mmol/l and 1.30 mmol/l. The hyperlipoproteinemia type IV (4.8%) was the most frequent, followed by Type IIa (4.6%), hypoalphalipoproteinemia (3.3%), and type IIb (0.2%). According to the National Cholesterol Education Program Adult Treatment Panel II, 4.1% of Korean adults needed the initial drug therapy and 10.8% the initial dietary therapy for hypercholesterolemia. The age and sex-specific treatment guidelines for hypercholesterolemia would make it possible that early intervention could be applied to atherosclerosis in Korean adults.

The Paragon CZE 2000 (Beckman Analytical, Milan, Italy) is an automatic dedicated capillary zone electrophoresis (CZE) system, producing a five-zone serum protein pattern with quantitative estimation of the zones. With the view of substituting this instrument for two previously used serum protein electrophoresis techniques, we planned to produce reference values for the "new" systems leading to compatible interpretation of the results. High resolution cellulose acetate electrophoresis with visual inspection and descriptive reporting (HR-CAE) and five-zone cellulose acetate electrophoresis with densitometry (CAE-D) were the previously used techniques. Serum samples (n = 167) giving "normal pattern" with HR-CAE were assayed with the CZE system, and the results were statistically assessed to yield 0.95 reference intervals. One thousand normal and pathological serum samples were then assayed with the CAE-D and the CZE techniques, and the regression equations of the CAE-D values over the CZE values for the five zones were used to transform the CAE-D reference limits into the CZE reference limits. The two sets of reference values thereby produced were in good agreement with each other and also with reference values previously reported for the CZE system. Thus, reference values for the CZE techniques permit interpretation of results coherent with the previously used techniques and reporting modes.

In recent years, an increase in the prevalence of allergic diseases has been reported, in industrialised countries. It is also a problem in non-industrialised countries, but its extent is less well documented. In this study, inhalant screening allergens (AlaTOP ® ), food screening allergens (FP5E ® ), and total and specific IgE were measured in 237 allergic patients (164 adults and 73 children) in order to examine the distribution of common allergens, the percentage of atopy/non-atopy among allergic children and adults in a developing country, Turkey, which has different environments and societies from western countries. We also evaluated the efficiency of automatic allergy screening tests in both groups. The sensitivity and specificity of AlaTOP ® in adults were 83% and 86%, respectively; these were 70% and 84%, respectively for FP5E ® , and the sensitivity and specificity of AlaTOP ® in children were 79% and 82%, while sensitivity and specificity of FP5E ® were 72% and 85%, respectively. The percentages of atopic male children (31%) were higher than in adults (21%). The reverse is true in adults. The most frequent allergens in childhood were Lolium perenne and cow milk, while in adults it was Lolium perenne . Total IgE levels were found to be statistically different between atopic and non-atopic subjects in adults (p < 0.001). This relationship was not found in children (p > 0.05). The sensitivity and specificity of total IgE in children were 57% and 67%, and in adults 84% and 67%, respectively. The lower specificity and sensitivity of total IgE level in children than in adults suggests that it is less useful for the diagnosis of allergy.

It is customary to assume that pre-metrological variation is negligible if all pre-metrological sources of variation have been standardised. The aim of this study was to quantify the pre-metrological variation of some biochemical quantities frequently measured in clinical laboratories. The experimental design considers the different sources of pre-metrological variation that usually act day-to-day on samples from patients. The results demonstrate that, for many quantities, the pre-metrological variance is not negligible; consequently, it is suggested that these variances should be taken into account when estimating the uncertainty of measurement of patients' results.