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Biomedical subjects

B G Blijenberg

Publications and source records attributed to B G Blijenberg.

At least 37 records · Page 2Linked to original sources

The value of screening tests in the detection of prostate cancer. Part I: Results of a retrospective evaluation of 1726 men.

OBJECTIVES: The ratio between free and total prostate-specific antigen (PSA) in serum (F/T ratio) was shown to improve the differentiation between prostate carcinoma and benign conditions in selected series of patients. In this study the F/T ratio was analyzed for its ability to improve the specificity of total serum PSA, digital rectal examination (DRE), and transrectal ultrasonography (TRUS) for the detection of prostate cancer in an unselected screening population of men identified in the Rotterdam population. METHODS: In 1726 men between 55 and 76 years old, 67 prostate carcinomas were detected by DRE, TRUS, and total serum PSA (Abbott IMx, Hybritech Tandem E). The DELFIA ProStatus PSA EQM and ProStatus PSA Free/Total assays (Wallac) were applied in retrospect to determine total and free serum PSA. Age, total prostate and inner zone volumes were taken into consideration. RESULTS: Sixty-seven carcinomas were detected, two by TRUS and three by DRE alone. Total serum PSA was the most important single predictor of prostate cancer, followed by DRE. The F/T ratio increased the specificity of total serum PSA in the PSA range between 4.0 and 10.0 ng/mL. However, this improved specificity was not significant, nor for gland volumes restricted to 50 mL or less. CONCLUSIONS: The combination of total serum PSA and DRE remains the standard for detection of prostate carcinoma in a screening population. Their specificity may be improved minimally by the F/T ratio, but not significantly in a sample of 1726 screened men. The threshold of the F/T ratio, and the optimal PSA range for its application, remains to be assessed prospectively.

Aged↗

The value of screening tests in the detection of prostate cancer. Part II: Retrospective analysis of free/total prostate-specific analysis ratio, age-specific reference ranges, and PSA density.

OBJECTIVES: The ratio between free and total prostate-specific antigen (PSA) in serum (F/T ratio) was shown to improve the specificity of total serum PSA for the detection of prostate carcinoma in selected populations. In this study, the value of the F/T ratio for screening of prostate cancer was compared with that of age-specific reference ranges for PSA and PSA density (PSAD) by a simulation experiment. METHODS: In 1726 men between 55 and 76 years old, 67 prostate carcinomas were detected by application of digital rectal examination (DRE), transrectal ultrasonography (TRUS), and total serum PSA. A serum PSA of 4.0 ng/mL or more, an abnormal DRE, or an abnormal TRUS were the indications to perform 308 biopsies. A simulation was performed in which an F/T ratio of 0.20 (ProStatus PSA Free/Total), age-specific PSA reference ranges, and a PSAD of 0.12 ng/mL/cc were used to study their capability to increase the specificity of total serum PSA in predicting prostate biopsy results. RESULTS: Using age-specific PSA reference ranges and DRE as indicators for biopsy, a reduction of 37% (113) of biopsies would have been obtained with a loss of detected cancers of 12% (11). For the use of PSAD and DRE, these numbers were 28% (96) and 11% (7), respectively. Application of a serum PSA of 4.0 ng/mL or more and an F/T ratio of 0.20 or less and an abnormal DRE as indicators for biopsy would reduce the number of biopsies by 37% (112) and the number of detected cancers by 11% (7). The biopsy to prostate cancer ratio of these simulations varied between 3.3 and 3.6. Minimal loss of cancer detection of 3% (2) with a reduction in the number of biopsies of 17% (53) is obtained when TRUS is omitted from the screening protocol. Selecting men by a total serum PSA value of 2.0 ng/mL for further diagnostic workup by TRUS and DRE would have reduced the number of biopsies by 30% (102), and the number of cancers detected by 6% (4). CONCLUSIONS: The most cost-effective protocol for screening prostate carcinoma appears to be prescreening by total serum PSA. The F/T ratio might be used to detect carcinomas in the PSA range below 4.0 ng/mL, but the best threshold remains to be assessed.

Age Factors↗

Creatinine and surveys: an assessment.

We analysed the results of surveys on creatinine held in The Netherlands during the years 1992, 1993 and 1994. Assay results of 113 samples were reviewed: 88 human sera and 25 samples of animal origin. The results of 5 creatinine assays, 4 based on the Jaffé reaction and 1 enzymatic procedure, are discussed. The enzymatic assay showed by far the best performance, while some of the Jaffé methods differed considerably. All results were evaluated by reference to a HPLC-based selected method for creatinine. Our study shows the need for caution when applying survey performance criteria for creatinine.

Animals↗

Prostate-specific antigen: its clinical use and application in screening for prostate cancer.

Prostate cancer in most European countries is the second most frequent cancer in males and the second most frequent cause of cancer death. Prostate specific antigen (PSA) is an important tumour marker, which relates to many aspects of this disease. It has been shown that PSA is helpful in the early diagnosis of prostate cancer and in this respect is superior to other available tests like rectal examination and transrectal ultrasonography. PSA is also helpful in staging of locally confined disease. It can be used to identify or exclude local extension of disease, if combined with T category and grade of differentiation determined on biopsy. The same parameters also give an indication of the presence of lymph node metastases, which may prevent unnecessary and invasive staging procedures in certain groups of patients with favourable prognostic factors and a low PSA value. PSA is less suitable as a marker for metastatic disease. Progression of untreated prostate cancer in various stages can be monitored by PSA. The true value of the marker in this respect is still underexplored. It may be possible that PSA will be shown to differentiate effectively between aggressive and non-progressive disease. In this respect, it could become an essential tool to identify those patients that may not require treatment at all. PSA is also a useful marker for therapy response. An elevation of PSA after radical prostatectomy indicates local or metastatic progression, which will occur within 1-2 years. PSA is an androgen dependent enzyme and decreases under endocrine treatment. It is unexplained why in spite of its endocrine dependent character, PSA rises with endocrine independent progression of prostate cancer.

Humans↗

The analytical and clinical performance of the new Boehringer Mannheim Enzymun-Test PSA assay for prostate-specific antigen.

A combined evaluation effort of the Boehringer Mannheim Research and Development and Evaluation Departments and the University Hospital Rotterdam is described regarding the new, fully automated Enzymun-Test PSA assay for prostate-specific antigen. The study consisted of an analytical and a clinical part. At both sites, the vast majority of intra-assay coefficients of variation ranged from 2 to 3% above prostate-specific antigen = 1 microgram/l. Below that concentration higher coefficients of variation were measured. Comparable results were obtained for the interassay imprecision. The analytical sensitivity (lower limit of detection) was found to be 0.02 microgram/l at both sites. Regarding the linearity of the assay no systematic drift to either elevated or lower values which increasing dilution was found. Deviations remained well in the range between 100 +/- 10%. The correlation with the Abbot IMx PSA assay as performed with a large set of clinical specimens revealed: y (= Enzymun) = 1.16x (= IMx) + 0.0; r = 0.985; n = 245. In this comparison study small differences between benign prostatic hyperplasia patients and prostate cancer patients were detected, perhaps partly based on the differences in recognition patterns of various molecular prostate-specific antigen forms in both assays. A follow-up after radical prostatectomy with 17 patients (50 serum samples) also showed a good comparability between the Enzymun-Test and the IMx assay. The limited check of the reference range resulted in data comparable to what can be found in the literature: out of 100 samples originating from healthy males, aged 20-60 years, 99 had prostate-specific antigen values lower than 4 micrograms/l. Based on our findings it can be concluded that the new Enzymun-Test PSA assay meets the current state-of-the-art criteria in prostate-specific antigen methodology.

Adult↗

Diagnostic analysis of total protein, albumin, white cell count and differential in ascitic fluid.

Accurate and precise procedures are described for the measurement of total protein, albumin, white cell count and differential in ascitic fluid. The total protein method (biuret) on the serum chemistry analyser, Bayer-Technicon Chem-1, was calibrated against the biuret reference method in the measuring range from 1-100 g/l, covering serum as well as ascitic fluid values. The albumin method (bromcresol green) on the Chem-1 was calibrated for the measurement range from 1-50 g/l against the new human plasma protein international reference preparations and compared to the nephelometric method on the Beckman Array, which was also calibrated against these reference preparations. A good correlation was obtained for total protein between the Chem-1 (y) and the biuret reference method (x) in 58 ascitic fluids (y = 1.02x -0.3; r = 1.00). A good correlation between the Chem-1 (y) and the Array (x) was also obtained for albumin (r = 0.99). The bromcresol green method, however, which is not fully specific, resulted in significantly higher results (y = 1.32x - 1.3). The immunochemical procedure is considered the more accurate and therefore the bromcresol green method is not suitable for the determination of albumin in ascitic fluids. The white cell count in ascitic fluid can be measured reliably by most haematology analysers if the sample is fresh and homogeneous, but the differential is flagged as a result of differing morphology. Handmade smears from ascitic fluid, however, show uneven distribution of cells and disturbed morphology.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

Multicentre evaluation of a new fully automated enzyme immunoassay for total prostate-specific antigen.

UNLABELLED: The evaluation is reported of a newly developed automated assay for measuring total prostate-specific antigen: Enzymun-Test PSA. Starting with a small field study, the study was extended to 74 laboratories in different countries. The median values for the intra-assay imprecision ranged from 5.0% (0.0-2.0 micrograms/l) to 2.5% (> 10.0 micrograms/l). For the inter-assay imprecision the results for the same ranges were 23.2 and 3.8%, respectively. The lower limit of detection, biological and functional sensitivity were 0.03, 0.1 and 0.25 micrograms/l, respectively. The linearity and dilution experiments showed acceptable data. The determined reference ranges (95% confidence intervals) were: men < 40 years: 0.1-1.3 micrograms/l, men 40-50 years: 0.2-2.0 micrograms/l, men 50-60 years: 0.2-3.0 and men > 60 years: 0.2-4.5 micrograms/l. Comparison of Enzymun-Test PSA with most present-day commercially available assays generally revealed very good correlations. IN CONCLUSION: the new Boehringer Mannheim Enzymun-Test PSA is compatible with the state-of-the-art for the measurement of total prostate-specific antigen.

Adult↗

[Variability of values of prostate-specific antigen determined with 6 methods].

OBJECTIVE: To illustrate the variability of serum Prostate Specific Antigen (PSA) and its causes in relevant clinical patient populations. SETTING: University Hospital Rotterdam, the Netherlands. DESIGN: Descriptive. METHODS: Six different methods of PSA analysis were applied to sera of 19 participants of a screening population, 20 patients after radical prostatectomy, and 15 newly diagnosed patients with a prostate carcinoma. The Hybritech Tandem-R value was chosen as the standard to compare the methods of analysis. Around a standard of 4.0 micrograms/l a range of 3.3 to 7.2 micrograms/l was found; around 10.0 micrograms/l a range of 8.7 to 18.5 micrograms/l. After radical prostatectomy the different methods of analysis agreed completely in only 5 out of 15 patients with respect to serum PSA. CONCLUSION: Because of a considerable variability in serum PSA values between different laboratories and methods of analysis, and of overlap between benign and malignant prostatic diseases, reference values of PSA should be handled with great care.

Adult↗

Prognostic significance of tissue polypeptide-specific antigen (TPS) in patients with advanced non-small cell lung cancer.

In this study, we evaluated the prognostic value of the tumour marker, tissue polypeptide-specific antigen (TPS), in 203 patients with non-small cell lung cancer (NSCLC), and related this to several other known prognostic factors. TPS was significantly correlated with lactate dehydrogenase (LDH), gamma-glutamyltranspeptidase and alkaline phosphatase, and the median level of TPS in patients with stage 4 disease was significantly higher as compared to stage 3A and 3B disease. In the univariate analysis, performance status, stage of disease, LDH, alkaline phosphatase, a histology of undifferentiated large cell carcinoma and TPS all had a statistically significant association with survival. Multivariate analysis showed that stage of disease, performance status, histology and TPS were the most important prognostic factors. TPS has prognostic significance for survival in patients with advanced NSCLC, independent from performance status and stage of disease.

Adult↗

Evaluation of a new tumour marker in patients with non-small-cell lung cancer: Cyfra 21.1.

The Cyfra 21.1 assay is a newly developed test which measures in serum a fragment of cytokeratin 19. We evaluated this marker in 212 patients with non-small-cell lung cancer (NSCLC), predominantly stage 3a-b and 4, and compared it with three other markers: carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and tissue polypeptide antigen (TPA). Sensitivities for Cyfra 21.1, TPA, CEA and SCC (using cut-off levels corresponding to a 95% specificity for benign lung diseases) were 40%, 40%, 42% and 19% respectively. The sensitivity of CEA was significantly higher in patients with adenocarcinomas compared with the other three markers, while the sensitivity of Cyfra 21.1 and TPA was significantly higher in patients with squamous cell carcinomas. The value of Cyfra 21.1 for monitoring disease during chemotherapy could be evaluated in 23 patients with squamous cell carcinomas. When the cases of lead time were included a concordance between clinical evaluations according to WHO response criteria and evaluations according to changes in the marker levels of 74% was found. The criteria defined for marker response were a 65% decrease in the marker level for a partial response and a 40% increase for progressive disease. In particular, increasing levels of this marker indicated usually disease progression. In conclusion, Cyfra 21.1 is a useful serum marker for patients with NSCLC, especially for disease monitoring of patients with squamous cell carcinoma during and after chemotherapy.

Adult↗

The accuracy of creatinine methods based on the Jaffé reaction: a questionable matter.

The determination of creatinine in serum based on the Jaffé reaction was evaluated with four current analysers. In particular, the comparability of results was determined also with survey specimens. Recalibration of 3 out of 4 modifications was necessary, based on the results of patient samples as verified with a HPLC-method. One of the methods proved to give an unacceptable scatter for the results in the lower range (30-150 mumol/l). A limited interference study (haemoglobin, lipids, bilirubin and acetone) and a method assessment with quality control sera supported the conclusion that the overall accuracy of creatinine methods based on the Jaffé reaction is questionable.

Calibration↗

Improvements in creatinine methodology: a critical assessment.

A large evaluation study, analytical as well as clinical, was performed on four published improvements for the determination of creatinine in serum. Two of the methods were based on the Jaffé reaction, the other two were enzymatic methods. Analytically, all four methods showed a similar performance. In the analysis of numerous specimens from advanced care departments, however, the methods performed differently. The two enzymatic procedures scored better than the two Jaffé methods, when compared with an HPLC-based reference method. However, even the best methods produced outliers and a larger scatter than that obtained with "normal" specimens.

Bilirubin↗

Quantitative urinalysis with a common predilution on a DuPont Dimension.

Urine was quantitatively analysed for sodium, potassium, creatinine, calcium, urea, uric acid, inorganic phosphate and magnesium in one manual central predilution. The analysis was implemented on a DuPont Dimension and the results were compared with those obtained with our analysers currently in use. Based on modified serum methods and their assessed linearities, the 8 urine constituents were analysed with high accuracy and reproducibility in a 6-fold diluted urine with DuPont reagents. The Dimension method correlated well with flame photometry for sodium and potassium; with the EPOS analyser for creatinine, calcium, uric acid, urea and inorganic phosphate; with atomic absorption spectroscopy for magnesium. All between-run coefficients of variation were smaller than 5%, except for the analysis of sodium in the lower part of the measurement range. However, a dilution ratio of 6 is an acceptable compromise when these 8 constituents are determined collectively from a common predilution, thereby covering the complete measurement ranges for these analytes in urine specimens. An additional dilution step is necessary for only a few urine samples (fewer than 1% of samples for calcium and urea and fewer than than 2% for inorganic phosphate). The combined analysis of these 8 constituents can be carried out only on untreated urine samples. Currently recommended pretreatments, such as acidification for calcium and inorganic phosphate analysis, and uric acid analysis under alkaline conditions, can be avoided.

Evaluation Studies as Topic↗

New approaches with the Chem-1 creatinine determination.

Three modifications of the Chem-1 determination of serum creatinine were tested. Two different algorithms developed for compensating the interference of bilirubin were compared with the current one by analysing bilirubin-enriched albumin solutions and 82 icteric serum samples. A number of known other interfering substances were also tested. The modification involving parallel bichromatic measurement plus bilirubin correction appeared to give the best performance. However, despite the improvements, the determination is not yet completely satisfactory.

Algorithms↗

The performance of the Chem-1 revisited: an evaluation after 3 years.

An evaluation of the Bayer-Technicon Chem-1 multitest analyzer is described over the period 1989-1992. Various aspects like daily use, running costs and quality assessment are discussed. The whole process regarding the performance, ranging from negative feelings in the first year to satisfaction in the third, is followed critically.

Chemistry Techniques, Analytical↗

Automated enzymatic methods for creatinine measurement with special attention to bilirubin interference.

Four enzymatic methods for creatinine measurement were evaluated on a DuPont Dimension automatic analyzer. Biomed Creatinine-Duo-UV (BIO) and Raichem Creatinine Reagent Enzymatic (RAI) start creatinine breakdown with creatinine iminohydrolase (EC 3.5.4.21) resulting in the formation of NH4+. The Boehringer Mannheim Creatinine PAP (BM1) and SopaChem Creatinine (SOP) start the breakdown of creatinine with creatininase (EC 3.5.2.10) which yields creatine. In order to reduce bilirubin interference, the BM1 method was modified to contain K4Fe(CN)6. This substance was added with reagent 1 (BM2) or with reagent 2 (BM3). All the enzymatic creatinine methods tested displayed good linearity for concentrations up to at least 1000 mumol/l. The BIO, BM3, RAI and SOP methods showed good stability of test outcome for the tested period of a week. The outcome of the BM1 and BM2 method increased continually with time. Only the results of the RAI method were diminished by the presence of lipids. The BM1, BM2, BM3 and SOP methods showed no interference with haemoglobin, whereas this increased the outcome of the BIO method and slightly decreased the results of the RAI method. Using spiked human albumin solutions it was found that the BIO, BM2, BM3 and RAI methods displayed good resistance to interference by bilirubin or ditauro-bilirubin. The outcome of the BM1 and SOP method was strongly decreased by both bilirubin and ditauro-bilirubin. When creatinine was measured in a panel of sera originating from 100 patients with bilirubin concentrations higher than 50 mumol/l, the obtained results were in close agreement with those found for the spiked human albumin solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

Bilirubin↗