European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies最新文献

This study describes the value of using the fraction of free prostate-specific antigen as a further marker in the early detection of prostate cancer. This newly introduced marker is compared to the usual battery of age-dependent total prostate-specific antigen, prostate-specific antigen density (microg/l x g tissue) and prostate-specific antigen velocity (microg/l x year). Determination of total prostate-specific antigen and free prostate-specific antigen was performed on fresh serum samples obtained from 3470 symptomatic patients aged 45-80 attending the Urology Clinics, or their General Practitioners. Among them, 310 patients had total prostate-specific antigen above the age-dependent cut-off, and/or free/total prostate-specific antigen under 11%, with different prostate-specific antigen densities and velocities. Only 147 patients complied to undergo biopsy: in 72 of those patients, benign prostatic disease was histologically confirmed, while in 75 patients primary prostate cancer was histologically confirmed. Total and free prostate-specific antigen levels were determined using the third generation DPCs prostate-specific antigen assay performed on the Immulite automated immunoassay instrument. Total prostate-specific antigen age reference values were adopted from Oesterling et al. (J Am Med Ass 1993; 270:860-4); the prostate-specific antigen density was considered suspicious of prostate cancer if it was greater than 0.15 microg/l prostate-specific antigen per gram tissue (Seaman et al. Urol Clin N Am 1993; 20:653); prostate-specific antigen velocity greater than 0.75 microg/l x year (Carter et al., J Am Med Ass 1992; 267:215) was considered suspicious for prostate cancer. Of the 147 patients, 75 had prostate cancer and 72 had benign prostatic hypertrophy. The difference between prostate cancer and benign prostatic hypertrophy was significantly reflected only by free/total prostate-specific antigen and prostate-specific antigen velocity. These parameters also provided the best sensitivity and specificity. Only these parameters proved to be significant when using a backwards logistic regression model (prostate-specific antigen velocity, p = 0.007 odds ratio 2.782; free/total prostate-specific antigen %, p = 0.016 odds ratio 2.678). Combinations of various parameters became significant when including free/total prostate-specific antigen, increasing prostate cancer detection to 88%. We conclude that free/total prostate-specific antigen is the most significant among prostate-specific antigen quantities (total age-dependent prostate-specific antigen, prostate-specific antigen density and prostate-specific antigen velocity). Adding this parameter to other prostate-specific antigen parameters improves the discrimination between prostate cancer and benign prostatic hypertrophy for the population at risk.

Dynamic interpretation of results is an alternative approach to the conventional cut-off procedure. Reference change limit is a valuable reference point to interpret dynamically tumour marker values when only very few serial results can be obtained from a patient after treatment. In this paper, a reference change limit of 2.0 microg/l was estimated for carcinoembryonic antigen in patients with complete remission of colorectal cancer. This figure means that a difference greater than 2.0 microg/l has at least a chance of being statistically significant (at 0.05 probability). As complementary information to the reference change limits, with more than four successive results, a simple time series model can be used to obtain predictive limits for the next observation.

Serum amyloid A, an apolipoprotein of high density lipoproteins, is also present to a lesser degree in low density lipoproteins and is co-localized with apolipoprotein B in atherosclerotic lesions. This study examined the effect of serum amyloid A on cellular affinity of low density lipoprotein in vitro. 125I-labelled low density lipoprotein, when loaded with recombinant serum amyloid A1 (acute phase isotype) or recombinant serum amyloid A4 (constitutive isotype), had enhanced binding to both human skin fibroblasts and a murine macrophage cell line, J774, while its degradation was slightly increased in both cells. The binding of oxidized low density lipoprotein to J774 cells was also enhanced by addition of recombinant serum amyloid A1 or serum amyloid A4, and degradation of oxidized low density lipoprotein was moderately enhanced by recombinant serum amyloid A1. The effects of recombinant serum amyloid A on cellular binding of labelled low density lipoprotein were not competed by non-labelled low density lipoprotein and were diminished in the presence of high density lipoprotein. These findings suggest that serum amyloid A in low density lipoprotein may promote association of low density lipoprotein with cells by non-specific adsorption, and high density lipoprotein may prevent such interactions by removal of serum amyloid A.

Epitestosterone, a C19-steroid with anti-androgenic activity, was determined in the plasma of 234 boys and men from the ages of 6-86 years, and in the prostate tissue of 15 men 55-82 years of age. It was documented that, while in adulthood the concentration of epitestosterone is about ten times lower than the concentration of testosterone, in the pre-pubertal period the level of epitestosterone is similar or even higher than that of testosterone. In the hyperplastic prostate tissue the content of epitestosterone is comparable to that of androstenedione, it is about twice as high as the content of testosterone and approximately half that of the content of dihydrotestosterone. At least in the case of pre-pubertal boys and in the prostatic tissue it is therefore possible to include epitestosterone into consideration as a regulatory factor for the androgen-dependent events.

In order to elucidate the question of free radical involvement in acute porphyric crisis, antioxidants were administered to two acute intermittent porphyria patients with long-standing recurrent attacks. Clinical condition and urinary excretion of porphyrins and porphyrin precursors were monitored before, during and after an eight week therapy with daily doses of vitamin E, beta-carotene, ascorbic acid, selenium, vitamin Q, acetylcysteine, mannitol and carnitine. Blood cell trace element profiles were followed. The administration of the compound antioxidant formula was found not to further impair the clinical or biochemical conditions of the patients but the incidence of the recurrent crises or the severity of the symptoms were not positively affected. Aberrant blood cell trace element profiles with increased granulocyte manganese were normalized during treatment, on cessation of the therapy again resuming the abnormal pretreatment patterns, which may suggest an origin in oxidative stress. No correlation was observed between the concentration of granulocyte manganese and the excretion of 5-aminolaevulinic acid. Indications for participation of this porphyrin precursor in a radical generating process leading to generalized mitochondrial superoxide dismutase induction, as conceivably signalled by increased intracellular manganese, were thus not obtained. The failure to note a clinical response to antioxidant therapy may be due to factors dependent upon dosage of, or interaction between, the antioxidant compounds given, or on restricted bioavailability of the antioxidants at critical anatomical sites, and does not per se invalidate the model of acute porphyria as a hyperoxidative condition.

We report on a 27-year-old healthy female with transient hyperphosphatasaemia of adulthood (it is the eighth case ever recorded). A maximum alkaline phosphatase activity of 1950 U/l, 11-fold the upper reference limit, was measured. The activity normalized within 11 weeks. Electrophoresis revealed the typical pattern for alkaline phosphatase isoenzymes observed in transient hyperphosphatasaemia of infancy: a fast-migrating liver isoenzyme and a bone isoenzyme. Contrary to the findings in transient hyperphosphatasaemia of infancy the liver isoenzyme did not precipitate with wheat-germ lectin whereas the bone isoenzyme partially bound to lectin. Biochemical features of transient hyperphosphatasaemia in an adult may be different from those in infancy. Recognition of an atypical pattern could help avoid unnecessary extensive investigations.

Insulin was assayed directly using radioimmunoassay and immunometric assay in 31 sera containing anti-insulin antibodies. Anti-insulin antibodies were determined by radio-binding-assay. Insulin measurements were compared with those of free (unbound to antibodies, polyethylene glycol precipitated) insulin measurements. Compared with free insulin concentrations, radioimmunoassay and immunometric assay yielded falsely increased insulin results. The degree of overestimation by radioimmunoassay and by immunometric assay correlated with the anti-insulin antibody value. Anti-insulin antibodies still remain a possible pitfall in the insulin-specific immunometric assays which are now being widely used.

The interference of buflomedil with the monoclonal and polyclonal EMIT d.a.u. amphetamine immunoassays was investigated. Urine samples collected from 20 patients taking 600 mg of buflomedil daily gave false positive results with the monoclonal EMIT d.a.u. assay, as did urine specimens collected 2 hours after the first oral dose of buflomedil. Conversely, no false positive results occurred with the polyclonal EMIT d.a.u. amphetamine assay. Urine samples with buflomedil added at concentrations greater than 100 mg/l gave false positive results with the monoclonal immunoassay. Buflomedil concentrations found in the patient urines (56-400 mg/l) failed to correlate to EMIT assay responses: this result suggests that one or more buflomedil metabolites, besides the unchanged drug, probably interfere in the monoclonal EMIT d.a.u. assay.

Two high performance liquid chromatographic methods (HPLC) with isocratic reversed-phase separation are presented for the determination of alpha-tocopherol (vitamin E) in serum. In the first method alpha-tocopherol acetate is used as internal standard, detection of absorbance is performed at 284 nm. In the second method tocol is used as internal standard, detection of fluorescence is performed with an excitation wavelength of 292 nm and emission wavelength of 325 nm. Both methods require a liquid-liquid extraction as sample preparation. The results of both HPLC methods have been tested by method comparison for n = 25 serum samples versus an isotope dilution-gas chromatography-mass spectrometry (ID-GC-MS) method using alpha-tocopherol-d6 as internal standard. The imprecision within-run was lower than 2.5% for the UV method and lower than 1% for the fluorescence method for both standards and serum pools. The between-run imprecision, obtained for serum pools, was below 5% for the UV method and not higher than 1.5% for the fluorescence method and not higher 1.8% for the ID-GC-MS. Recovery experiments performed by spiking pool sera with alpha-tocopherol showed recoveries between 98.5% and 100.6% for all methods studied. The result of the method comparison was a coefficient of correlation of r = 0.998 for the HPLC method with fluorescence detection to the ID-GC-MS reference method and a coefficient of correlation of r = 0.981 for the HPLC method with UV detection to the ID-GC-MS reference method. Both methods presented are useful for the analysis of alpha-tocopherol in patient samples. If detection of fluorescence is used, imprecision and inaccuracy of the HPLC method are comparable to the ID-GC-MS chosen as reference method.