[The biomarkers BNP and NT-proBNP]. / Die Biomarker BNP und NT­proBNP.

The present review of the biomarkers BNP and NT-pro-BNP is published in the series "biomarkers" of the Zentralblatt für Arbeitsmedizin, Arbeitsschutz und Ergonomie, which deals with the increasing use of the determination of specific markers in so-called manager preventive and check-up examinations. In principle, BNP and NT-pro-BNP are fundamentally suitable as markers for diagnosing acute and chronic heart failure and for assessing the course. In this context these show a high sensitivity and specificity.

Standard values of the upper body posture in healthy adults with special regard to age, sex and BMI.

In order to classify and analyze the parameters of upper body posture in clinical or physiotherapeutic settings, a baseline in the form of standard values with special regard to age, sex and BMI is required. Thus, subjectively healthy men and women aged 21-60 years were measured in this project. The postural parameters of 800 symptom-free male (n = 397) and female (n = 407) volunteers aged 21-60 years (Ø♀: 39.7 ± 11.6, Ø â™‚: 40.7 ± 11.5 y) were studied. The mean height of the men was 1.8 ± 0.07 m, with a mean body weight of 84.8 ± 13.1 kg and an average BMI of 26.0 ± 3.534 kg/m2. In contrast, the mean height of the women was 1.67 ± 0.06 m, with a mean body weight of 66.5 ± 12.7 kg and an average BMI of 23.9 ± 4.6 kg/m2. By means of video rasterstereography, a 3-dimensional scan of the upper back surface was measured when in a habitual standing position. The means or medians, confidence intervals, tolerance ranges, the minimum, 2.5, 25, 50, 75, 97.5 percentiles and the maximum, plus the kurtosis and skewness of the distribution, were calculated for all parameters. Additionally, ANOVA and a factor analyses (sex, BMI, age) were conducted. In both sexes across all age groups, balanced, symmetrical upper body statics were evident. Most strikingly, the females showed greater thoracic kyphosis and lumbar lordosis angles (kyphosis: Ø â™€ 56°, Ø♂ 51°; lordosis: Ø â™€ 49°, Ø♂ 32°) and lumbar bending angles (Ø â™€ 14°, Ø♂ 11°) than the males. The distance between the scapulae was more pronounced in men. These parameters also show an increase with age and BMI, respectively. Pelvic parameters were independent of age and sex. The upper body postures of women and men between the ages of 21 and 60 years were found to be almost symmetrical and axis-conforming with a positive correlation for BMI or age. Consequently, the present body posture parameters allow for comparisons with other studies, as well as for the evaluation of clinical (interim) diagnostics and applications.

Symmetrical dental occlusion blocking - changes of body sway and weight distribution in healthy subjects across 4 age decades.

OBJECTIVES: Symmetrical dental occlusion blocking is used in dentistry as a quick diagnostic tool to test for potential influences of the craniomandibular system on body sway and weight distribution. This study presents the changes of body sway and pressure distribution in healthy subjects, free of a temporomandibular dysfunction (TMD). Immediate effects between occlusal blocking and rest position on body sway and body weight distribution in general, as well as for both genders and for four age decades will be evaluated. MATERIALS AND METHODS: 725 (396f/329 m) subjects (neither subjective signs of TMD nor acute/chronic complaints in the musculoskeletal system) volunteered (21 to 60 years) while both genders were divided into four age groups according to decades. A pressure measuring platform was used. Body sway and weight distribution were recorded in two dental occlusion conditions (a) in rest position and (b) symmetrical blocking (bicuspid region) by cotton rolls. RESULTS: Both, the frontal sway and the sagittal sway reduced by 0.67 mm (t(724) = - 3.9 (p <  0.001)) and by 0.33 mm (t(724) = - 3.4 (p <  0.001)). The relative pressure under the left forefoot increased by 0.33% (t(724) = 2.88 (p <  0.001)) and the relative pressure overall under the forefoot increased by 0.67% (t(724) = - 3.4 (p <  0.001)). Gender-specific, age-specific and BMI-specific reactions could not be identified. CONCLUSIONS: Subjects, free of any TMD and with no complaints of the musculoskeletal system, show small changes of the body sway and weight distribution when biting symmetrically on a cotton roll. These changes are independent of age, gender or body mass index (BMI). Due to the relative large sample size, the presented results can also be seen as norm values when body sway is used as an additional assessment of a TMD.

Systematic changes of the static upper body posture with a symmetric occlusion condition.

BACKGROUND: Temporary occlusal changes and their influence on the upper body statics are still controversially discussed. Furthermore, concrete statements on whether age- or gender-specific differences in neurophysiological reactions exist are missing. Therefore, it is the aim of this study to evaluate the immediate effects of a symmetrical occlusion blocking on the upper body posture. These effects shall be investigated for both genders and for a larger age range. METHODS: In this study, 800 (407f/393 m) subjects volunteered aged from 21 to 60 years. Both genders were divided into four age groups according to decades. The three-dimensional upper body posture was measured by using the rasterstereography (ABW-Bodymapper). The habitual static posture was measured in two dental occlusion conditions (a) in rest position and (b) symmetrical blocking in the bicuspid region by cotton rolls. RESULTS: A significant reduction of the trunk length (0.72 mm; p <  0.001), an increase of the lumbar (0.30°; p <  0.001) and the thoracic bending angle (0.14°; p = 0.001), a reduction of the spinal forward decline (0.16°; p <  0.001) and a reduction of the scapular distance (0.36 mm; p = 0.001) was found. Gender-specific reactions can only be recorded in scapular distance, in that regard men reduce this distance while over all age groups women did not show a significant change. DISCUSSION: Slight gender- and age-independent reactions due to a symmetric occlusion blockade are shown: A gender independent reaction of the spinal related variables in the sagittal plane (thoracic and lumbar flexion angle, trunk length, spinal forward decline). In addition, a gender specific change of the shoulder blade distance could be observed, where men reduced the distance while female did not show a change. However, since these reactions are of a minimum amount, it can be concluded that neurophysiological compensation mechanisms work equally well regardless of age and sex, and the upper body posture of healthy people changes only very slightly due to a temporarily symmetrical altered bite position.

Kinematic posture analysis of orthodontists in their daily working practice.

PURPOSE: The aim of this study is to conduct a kinematic analysis of occupational posture in orthodontists. METHODS: A representative sample of 21 (13 female/8 male) residents in orthodontics and orthodontists was studied. The CUELA system collects kinematic data of the occupational posture. Alongside the kinematic analysis, the tasks performed on-site were also subject to a detailed computerized analysis. Data analysis comprised the evaluation and comparison of joint angle distribution in accordance with ergonomic standards categorized as neutral, moderate or awkward posture. RESULTS: The most common activities were executed in a seated position. During "treatment" (28% of total time) participants most often worked with a straight back (84.7%), whereas a "bent or twisted" torso posture was observed 23.4% of the time. For head and cervical spine, the 75th and 95th percentiles presented worse (higher) values during treatment as compared to non-orthodontic activities. The seated position next to the patient during treatment showed a stronger inclination of the thoracic spine to the right and an inclination of the lumber spine to the left. CONCLUSIONS: Orthodontists do take characteristic postures during treatment activities with highest angle values. The postures differ in the area of head and cervical spine with regard to the various activities carried out in the 3 categories.

Comparison of a new microbiological assay with a standard high-performance liquid chromatographic method for determination of vitamin B6 in serum.

BACKGROUND: A high-performance liquid chromatographic (HPLC) assay for vitamin B6 in human serum was compared with a novel microbiological assay (ID-Vit) that uses microtitre plates precoated with a specific microorganism, thus avoiding numerous problems associated with the use of stock cultures utilized by common other microbial assay mit B6. METHODS: Data obtained using HPLC were compared with 1D-Vit results in 170 healthy individuals and in 68 patients with coronary artery disease (CAD, 37 with acute coronary syndrome [ACS], 31 with stable CAD). Regression and Bland-Altman analysis were performed. Homocysteine in CAD patients was measured by HPLC. RESULTS: The ID-Vit assay correlated well with the HPLC assay (Pearson's r = 0.89 [p < 0.0001] in healthy and 0.82 [p < 0.001] in CAD individuals). Bland-Altman analyses revealed good agreement between the results of both methods in both cohorts, with > or = 95% of all values grouping within the lines of agreement. In CAD patients, mean homocysteine values did not differ between stable CAD and ACS and were normal. Thirty-seven percent of CAD patients had estimated glomerular filtration rates (GFR) below 60 mL/min/1.73m2. GFR correlated inversely with homocysteine levels (r = -0.80, p < 0.001) whereas neither HPLC nor ID-Vit values for B6 did. CONCLUSIONS: ID-Vit assay and the HPLC standard are in very good agreement. The new assay can easily be automated and is less laborious than common microbiological assays. The lack of correlation between B6 vitamin and homocysteine can be accounted for by the fact that mean vitamin B6 in our CAD patients was in the normal range and that a relevant percentage of patients had chronic renal disease.

Tuberculosis skin test, but not interferon-γ-releasing assays is affected by BCG vaccination in HIV patients.

OBJECTIVE: Of this study was to compare the results of tuberculin skin test (TST) with two interferon-γ releasing-assays (IGRA) in a cohort of HIV positive patients, to analyze impact of prior Bacille-Calmette-Guérin (BCG)-vaccination. METHODS: Prospective cross sectional study, enrolling only asymptomatic adult HIV infected outpatients from a large German University hospital clinic. All participants were simultaneously tested for latent tuberculosis infection (LTBI) by QuantiFERON-TB Gold, T-SPOT.TB and TST. Only individuals with available definite results (positive/negative, indeterminates excluded) from all three test systems and recalling BCG-vaccination status by interview questionnaire were evaluated. RESULTS: From 286 study participants, 133 were evaluable; BCG-vaccination history was positive for 18 individuals, and negative for 115. The proportion of individuals with a positive TST was significantly higher for vaccinated (n = 6, 33.3%) than for unvaccinated individuals (n = 13, 11.3%, p = 0.013). There were no significant differences in the proportion of patients with CDC stage C, origin from a TB endemic country or in the CD4 count between the two groups. CONCLUSION: TST but not IGRAs interfered significantly with prior BCG vaccination in a cohort of HIV infected individuals from a low prevalence TB country. Therefore IGRA should preferentially be used for LTBI-testing in BCG-vaccinated adult HIV-patients.

Value of Procollagen Type I Aminoterminal Propeptide in Women with Breast Cancer with regard to Metastases.

Background. The aim of this study was to show the importance of the bone marker procollagen type 1 aminoterminal propeptide (P1NP) in detecting bone metastases in women suffering from breast cancer. We furthermore investigated to what degree P1NP is correlated to the degree of bone metastases, and if P1NP is increased in patients with metastases other than bone. Patients and Methods. We analyzed 80 serum samples of women (17 premenopausal/63 postmenopausal) with breast cancer. Therefore we used a specific immunoassay "ELECSYS 2010" by Roche Diagnostics. We divided our group of patients with regard to menopausal status, sites of metastases and number of bone metastases. Results. As a result we found higher concentrations of P1NP in women with radiologically confirmed bone metastases (median: 125.75 ng/mL) in comparison to the collective without bone involvement (median: 73.61 ng/mL). However, both groups showed values above the applied cutoff values of median 27.8 ng/mL for premenopausal women and median: 37.1 ng/mL for the postmenopausal group due to the fact that all patients had cancer. Furthermore higher P1NP concentrations were found in women with more than 5 sites of bone metastases (median: 183.9 ng/mL) than in patients with only one site of bone metastases (median: 37 ng/mL). Also patients with no bone involvement but other sites of metastases showed quite high P1NP concentrations (median: 73.61 ng/mL). Conclusion. The marker of bone turnover procollagen type 1 aminoterminal propeptide can be considered as a useful tool for estimating the extent of bone involvement and for the detection of bone metastases. P1NP cannot replace conventional methods for detecting bone metastases such as radiological methods but it can help clarify unclear radiological results. This study does not take into account the change of P1NP concentration during the course of therapy.

Alpha-1-Fetoprotein (AFP): international proficiency study with different test systems.

BACKGROUND: The present proficiency study aimed to elucidate the comparability and reliability of test systems for the determination of AFP concentrations. METHODS: 25 laboratories using 8 different commercial test systems used liquid BIOREF-AFP control serum in their routine internal quality control over a period of one year. For statistical analysis the results were collected centrally. RESULTS: The statistical analysis of the test results revealed considerable variation for the different laboratories. The deviations of the mean values of different laboratories from the overall mean value varied between 0.1 and 26.1%, and for most of the laboratories the deviation was round about 10%. The precision of measured values in the individual laboratories was in most cases acceptable: Nevertheless, the coefficients of variation of the individual laboratories ranged from 13 to 16.1%. CONCLUSIONS: In conclusion, this study indicates that AFP results vary between different laboratories albeit an international standard for AFP is available. Therefore, every laboratory should participate in external ring studies and should use a quality control serum independent of the test kit manufacturer for the internal quality control.

Value of TRAcP 5b as a diagnostic marker for detection of bone metastases in patients with breast cancer.

BACKGROUND/AIMS: The aim of the study was to test the bone resorption marker TRAcP 5b regarding its suitability for detection of bone metastases in breast cancer patients. PATIENTS AND METHODS: Serum samples from a total of 101 patients with histologically proven breast cancer and from 100 healthy probands were analyzed. The patients were divided into three groups: eight patients without osseous involvement, 65 patients with untreated bone metastases, 28 patients whose bone metastases were treated with bisphosphonate therapy. RESULTS: The TRAcP 5b concentration was significantly higher in breast cancer patients compared to healthy probands. It was not possible to demonstrate a statistically significant difference in the TRAcP 5b concentration if osseous metastases in breast cancer patients were present or not. CONCLUSION: Our research cannot support the claim that TRAcP 5b could be useful as a diagnostic tool for the detection of bone metastases in patients with breast cancer.

Procollagen type 1 amino-terminal propeptide: a marker for bone metastases in prostate carcinoma.

BACKGROUND: The objective of this study was to assess the utility of the bone formation marker procollagen type 1 amino-terminal propeptide (P1NP) in indicating bone metastases in patients with prostate carcinoma. Alkaline phosphatase (AP) and prostate-specific antigen (PSA) were measured as a comparison. PATIENTS AND METHODS: The serum samples of 100 patients were analysed using a specific immunoassay. The patients were divided into three groups, 32 patients with benign prostate hyperplasia (BPH), 38 patients with prostate carcinoma and 30 patients with prostate carcinoma with bone metastases. RESULTS: PINP concentrations were elevated in about 87% of the patients with confirmed bone metastases, the P1NP levels were significantly (p < or = 0.001) higher (median: 194.7 ng/ml) than in the patients without bone involvement (median: 38.0 ng/ml) and the BPH patients (median: 42.2 ng/ml), who both presented P1NP levels within the normal range. CONCLUSION: P1NP is a reliable predictor of the presence or absence of bone metastases in prostate carcinoma.

Value of procollagen type 1 amino-terminal propeptide in patients with renal cell carcinoma.

BACKGROUND: The aim of the study was to investigate whether the bone turnover marker procollagen type 1 amino-terminal propeptide (P1NP) could be useful for the early detection of bone metastases in patients with renal cell carcinoma (RCC) and if chemotherapy influences P1NP concentrations in patients with bone metastases. PATIENTS AND METHODS: Serum samples of 36 patients were analyzed using a specific immunoassay. The patients were divided into three groups: 24 patients without metastatic spread, 6 patients with untreated bone metastases and 6 patients who had received sorafenib. RESULTS: The P1NP concentration was significantly higher (p< or =0.001) in the patients with bone metastases (median: 396.10 ng/ml) than in those without bone involvement (median: 35.53 ng/ml). The patients treated with sorafenib showed levels within the normal range (median: 28.96 ng/ml). CONCLUSION: P1NP is a significant diagnostic marker for the development of bone metastases in patients with RCC and could help to evaluate the progress of chemotherapy.

[Comparison of two methods for rapid determination of C-reactive protein with the Tina-quant].

C-reactive protein (CRP) as an acute phase protein is an important diagnostic marker for the presence and course of human processes. Out of the acute phase proteins it is one of those the concentrations increase most rapidly with its sensitivity being superior to other markers of inflammation, such as leukocytosis, erythrocytic sedimentation rate, and fever. This study compared two-point-of-care assays with the standard laboratory method Tina-quant CRP processed on a Hitachi 917: the immunofiltration assay NycoCard CRP Whole Blood and the turbidimetric immunoassay Micros CRP. Both methods are carried in the presence of a patient, by using capillary or venous blood. Seventy-eight blood samples were analyzed first in the standard laboratory routine and then by both rapid test assays. The precision of both assays was determined from the confidence interval. The results were statistically analyzed by arithmetic standard deviation mean method, variation coefficient, Spearman correlation index, Wilcoxon and Bland-Altman tests, and Passing-Bablock regression. NycoCard CRP Whole Blood showed a correlation coefficient of R = 0.9838; the precision had a coefficient of variation of CV = 1.8759% while As compared with Tina-quant CRP had R = 0.9934 and CV = 0.9160%. Both assays indicated the same results as Tina-quant CRP. Both Tina-quant CRP and NycoCard CRP Whole Blood give the best fit for the rapid determination of CRP.

[The significance of TU M2-PK tumor marker for lung cancer diagnostics].

The purpose of the study was to investigate significance of the tumor marker pyruvate kinase Tumor M2 (Tu M2-PK), in diagnostics, monitoring of treatment, and evaluation of its effectiveness in patients with lung cancer (LC). This is an isoform of the glycosile enzyme pyruvate kinase, existing as an active dimer and less active tetramer. The expression of the less active form is typical of tumor cells; its blood level can be measured. The subjects of the study were 140 patients with LC of various histologic types. Serum levels of certain tumor markers (Cyfra 21-1, NSE, SCC, and Tu M2-PK) were measured; Tu M2-PK level was determined by ELISA test from ScheBoTech, a two-stage sandwich immunoassay using one type of antibodies. The marker concentration was also determined in 195 healthy volunteers (control group.) The maximum concentration of Tu M2-PK was 12.9 U/ml, determined with 95% specificity. 78% of the patients with small-cell carcinoma, 73% of patients with adenocarcinoma, and 81% of patients with non-small cell lung carcinoma displayed increase of Tu M2-PK serum concentration; this concentration was within normal limits in patients with nonmalignant diseases (e.g. bronchitis or tuberculosis). Thus, patients with lung carcinoma display a pathologic increase of Tu M2-P level. Measurement of Tu M2-P may be useful in patients with suspected LC; this marker may be of greater diagnostic significance than SCC or NSE.

Value of tumour and inflammatory markers in lung cancer.

The aim of this study was to evaluate the individual diagnostic utility of tumour and inflammatory markers in patients with different pulmonary diseases. The usefulness of neuron-specific enolase (NSE), carcino-embryonic antigen (CEA), serum pro-gastrin releasing peptide (ProGRP) and CYFRA 21-1, as tumour markers, and C-reactive protein (CRP) and tumour necrosis factor-alpha (TNFalpha) as inflammatory markers for diagnosis, treatment and monitoring of patients with different pulmonary afflictions was investigated. Eighty healthy individuals were also included. Serum samples were also obtained from 20 patients suffering from bronchitis, 20 with lung fibrosis and 30 with sarcoidosis. Moreover, serum marker levels were analyzed in 139 patients with different pulmonary malignancies: 29 patients with adenocarcinoma, 30 patients with squamous cell carcinoma, 80 patients with small cell lung cancer (SCLC). All tumour markers showed significantly elevated values in malignant diseases. The levels of ProGRP in patients with benign diseases were significantly higher than those in the healthy group (35.4 +/- 6.6 compared with 21.3 +/- 9.2 pg/ml respectively). The serum ProGRP levels were elevated in SCLC patients (1673.9 +/- 706 pg/ml). The elevation was significantly higher than that of the benign reference group. The acute phase response had a wide range in patients with malignant tumours. Serum CRP levels were significantly higher in patients with SCLC (38.5 +/- 7.6 mg/dl) than in the benign reference group. In conclusion, when serum tumour markers are abnormally elevated in patients with lung cancer, CEA, CYFRA 21-1, NSE and ProGRP are useful clinical markers, good indicators of disease extent and may have important prognostic value. In particular, NSE and ProGRP have a very high sensitivity for SCLC detection.

Saphenous vein interposition as a salvage technique for complex vascular situations during renal transplantation.

The shortage of donor organs for renal transplantation leads to the necessity of accepting organs with vascular disadvantages, such as venous difficulties (eg, shortness, disrupted vein after explantation) or arterial problems (eg, iatrogenic vascular accidents, arterial plaques, hemodynamically relevant polar arteries) and horseshoe kidneys. Consequently, such organs may not be considered for transplantation. Surgeons still have the ability to use such organs by saphenous vein interposition. This study focused on the frequency of vascular difficulties in 100 randomly selected kidney transplantations and their outcomes after arterial or venous saphenous vein interposition.

Phospholipids, tumour marker and beta-CrossLaps in diagnosis of gastric carcinoma.

INTRODUCTION: The aim of this study was to evaluate the effectiveness of the serum tumor marker levels of CEA, CA 19-9, CA 72-4 and beta-CrossLaps in gastric cancer patients. As an additional parameter, we investigated the membrane phospholipid profile of gastric cancer patients. MATERIALS AND METHODS: We measured the tumor marker and phospholipid concentrations in 40 patients suffering from gastric cancer, 12 patients suffering from pancreatitis and 40 patients with gastric ulcera. We used the Elecsys 2010 enzyme analyser to determine the concentrations of CEA, CA 19-9, CA 72-4 and beta-CrossLaps. Phospholipid fractions were determined by HPLC. RESULTS: Preoperative serum levels of CEA, CA 19-9 and CA 72-4 showed sensitivities of 47.5%, 68% and 76%, respectively. The sensitivity of beta-CrossLap was 63% for non-metastatic and 76% for metastatic gastric cancer. The phospholipid fraction of phosphatidyl ethanolamine showed elevated concentrations. CONCLUSION: Additional prognostic information can be obtained using the combined assay of these tumor markers in gastric cancer patients.

Pro-gastrin-releasing peptide (Pro-GRP), a tumor marker for small cell lung cancer.

INTRODUCTION: Gastrin-releasing peptide (Pro-GRP), a member of the bombesin family of peptides, has been shown to have mitogenic activity in small cell lung carcinoma (SCLC), and to be produced by SCLC in an autocrine fashion. We investigated the usefulness of serum pro-gastrin-releasing peptide (Pro-GRP) as a tumor marker for diagnosis, treatment and monitoring of patients with small cell lung cancer (SCLC). MATERIALS AND METHODS: This study comprised 80 healthy individuals. Serum samples were also obtained from 80 patients with small cell carcinoma, 20 with chronic bronchitis, 30 with sarcoidosis and 20 with lung fibrosis. The cut-off level of serum Pro-GRP was set at 34.2 pg/ml. RESULTS: The levels of Pro-GRP in the patients with benign diseases were significantly higher than those in the healthy group. The serum Pro-GRP levels were elevated in SCLC patients. The elevation was significantly higher than that of the benign reference group. CONCLUSION: These results show that Pro-GRP may be a potential tumor marker for small cell lung carcinoma.

Complexed PSA in routine diagnosis.

INTRODUCTION: Prostatic tumor tissue produces a more complex form of PSA (cPSA) than free PSA (fPSA). For the early detection of prostate cancer, cPSA is supposed to be more sensitive than the ratio of fPSA and tPSA. The aim of the study was to evaluate the diagnostic value of cPSA in the early detection of malignant prostatic tumor. MATERIALS AND METHODS: We evaluated the new cPSA test comparing it with the already routinely used fPSA and tPSA test. The study comprised a total of 100 patients with different urological symptoms attending the Division of Urology, University of Frankfurt, Germany. Biopsy and histological examination were performed in all cases. The histological report was compared with the laboratory results obtained by immunological and electrochemiluminescence methods. RESULTS: Forty-one had a benign tumor of the prostatic gland and 59 had a malignant process diagnosed by histological examination. The cut-off level for cPSA was at 2.3 ng/ml. Within a range of 2.0-4.0 ng/ml tPSA and a cut-off of 2.3 ng/ml for cPSA we found a tumor sensitivity of the test in 92%, proved by the histological report. cPSA allows the detection of a malignant process at an earlier stage than tPSA and even within a "normal-range" of tPSA between 2.0-4.0 ng/ml. A concentration of tPSA between 4.1 and 10 ng/ml represents a grey zone. With measurement of cPSA we achieved, in 71% of our cases, a more specific result than in obtaining the PSA ratio. We did not observe any adverse result in the concentration of cPSA concerning manipulation of the prostatic gland as seen before in the measurement of fPSA. cPSA is much more stable regarding transportation and storage. There is no loss of concentration level observed up to -20 degrees C, whereas fPSA shows a loss of 10%. CONCLUSION: We conclude that the new tumor marker cPSA is more specific in the concentration range of tPSA from 2.0-4.0 ng/ml, as well as in the grey zone between 4.0-10 ng/ml.