Lack of interrelationship between the effects of dietary factors and food withdrawal on carcase quality of broiler chickens

PURPOSE: We conducted this study to examine differences in characteristics of immunoreactivity for free PSA and alpha(1)-antichymotrypsin complex PSA (ACT-PSA) as well as in compositions and concentrations of PSA reference materials among commercially available PSA kits. METHODS: Fractionated serum samples using a Sephacryl S-200 column were measured by Tandem-R, Delfia-PSA, Ab bead PSA, ACS-PSA, Markit-M and gamma-seminoprotein (gamma-Sm) kits. The calibrators of Tandem-R, Delfia-PSA, Ab bead PSA and Markit-M were fractionated by the same method and measured by Tandem-R. The calibrators of Delfia-PSA, Ab bead PSA and Markit-M and control serums of ACS-PSA were measured by Tandem-R. RESULTS: Although the characteristic of immunoreactivity of Tandem-R, Delfia-PSA, and Ab bead PSA were found to be similar, they were not shown identical. ACS-PSA was proved to recognize free PSA greater than above three PSA kits, while Markit-M could scarcely detect free PSA. gamma-Sm recognized only free PSA. The calibrators of Tandem-R, Delfia-PSA, Ab bead PSA and Markit-M were proved to be only free PSA. The linear correlation was obtained between Tandem-R and Delfia-PSA or Ab bead PSA or Markit-M. The ratio of Delfia-PSA to Tandem-R, Ab bead PSA to Tandem-R and Markit-M to Tandem-R was 0.66, 0.93 and 2.2, respectively. With regard to relation of ACS-PSA and Tandem-R, two ratios of 0.22 and 0.25 were obtained between the two kits according to the different concentrations of control sera. CONCLUSION: The present studies suggest that the difference in PSA values among the commercial PSA kits results from (1) different characteristics of immunoreactivity for ACT-PSA and free PSA among PSA kits, (2) compositions of PSA calibrators among the kits, and (3) different concentrations of PSA calibrators among the kits.     

Percent free prostate-specific antigen in assessing the probability of prostate cancer under optimal analytical conditions

Although general consensus exists that percent free prostate-specific antigen (PSA) is superior to total immunoreactive PSA for prostate cancer (CaP) detection, its diagnostic performance is not yet well established. Analytical problems may account for difficulties in evaluating percent free PSA because the free PSA concentration is substantially lower than that of total PSA. The aim of the present study was to establish the diagnostic performances of the IMMULITE percent free PSA assay from Diagnostics Products Corp. under experimental conditions optimized to minimize analytical variability. Eighty-five patients with untreated primary CaP and 261 with untreated benign prostate hypertrophy (BPH) were prospectively enrolled. The Diagnostics Products IMMULITE total (Third Generation) and free PSA were measured by the same technician, using the same instrument and the same reagent batch. We calculated the post-test probability to express how the likelihood of the diagnosis of CaP changed after the percent free PSA was determined. Areas under the ROC curves of percent free PSA were better than those of total PSA in every evaluated range of total PSA. The percent free PSA could have reduced the rate of unnecessary biopsies by 47% in patients with total PSA >/=4 microg/L with only 3.8% false-negative results. The post-test probability of percent free PSA was, however, <50% in men 50-70 years of age, using cutoff points providing sensitivity from 99% to 80%. Percent free PSA is superior to total PSA in distinguishing primary CaP from BPH in patients with total PSA between 2 and 30 microg/L. In men with low total PSA, the diagnostic performance of the percent free PSA assay may be optimized by controlling methodological variability. The percent free PSA assay is effective in reducing the rate of unnecessary biopsies in men with total PSA >4 microg/L. However, the post-test probability provided by percent free PSA is relatively low in asymptomatic patients 50-70 years of age.     

Analytical and clinical performance characteristics of Tandem-MP Ostase, a new immunoassay for serum bone alkaline phosphatase

The performance characteristics of the Tandem-MP Ostase assay, a new microplate immunoassay for bone-specific alkaline phosphatase (bone ALP; EC 3.1.3.1) in human sera, are described. Bone ALP is bound to streptavidin-coated microwells by a single biotinylated anti-bone ALP monoclonal antibody. Antigen is detected by the addition of p-nitrophenyl phosphate. The assay is performed at room temperature in <90 min. Imprecision was 2.3-6.1% with a detection limit of 0.6 microg/L. Method comparison of bone ALP measurements with the Tandem-MP Ostase assay and the mass-based Tandem-R Ostase assay (n = 285) indicated regression statistics of Tandem-MP Ostase = 1.03 Tandem-R Ostase + 0.22 microg/L, S(y/x) = 4.0 microg/L, r = 0.97. Serum bone ALP values in apparently healthy men and in pre- and postmenopausal women were also similar between the two Ostase assay formats. Liver ALP reactivity determined using the slope and heat inactivation methods was similar in both Ostase assays. Liver ALP reactivity ranged from 3 microg/L (heat inactivation) to 6 microg/L (slope method) per 100 U/L of liver ALP activity, whereas bone ALP reactivity was 37 microg/L per 100 U/L of bone ALP activity, indicating a liver ALP relative reactivity of 8.1-16.2%. Similar results were obtained with the Alkphase-B bone ALP immunoassay. The Tandem-MP Ostase bone ALP assay demonstrated increased concentrations of serum bone ALP in conditions where bone metabolism is increased and showed a rapid, temporal decrease in serum bone ALP in Paget disease patients on bisphosphonate therapy. In conclusion, the Tandem-MP Ostase assay for serum bone ALP is a rapid, simple, robust nonisotopic alternative to the Tandem-R Ostase immunoradiometric assay that provides an accurate and sensitive assessment of bone turnover.     

Active site mutants of human herpesvirus-6 proteinase

OBJECTIVES: To assess the comparability of the Hybritech Tandem-R and Abbott AxSYM PSA assays in the setting of a hospital laboratory changing methods of PSA assay. METHODS: A total of 115 serum samples were tested simultaneously with both reagent kits. These include samples from patients evaluated for screening, benign prostatic hyperplasia, and follow-up of prostate cancer. RESULTS: The outcomes of the Hybritech Tandem-R PSA test ranged from 0.0 to 48.3 ng/mL with a median value of 2.4 ng/mL (mean 3.48, SD 5.46). The outcomes of the Abbott AxSYM PSA test ranged from 0.0 to 49.33 ng/mL with a median of 2.22 ng/mL (mean 3.82, SD 5.59). The outcomes of the two assays were found to be highly correlated by the Pearson correlation coefficient (r = 0.9942). When samples were divided according to PSA levels of 0.0 to less than 2.5, 2.5 to less than 4.0, 4.0 to less than 10.0, and 10.0 to less than 25.0 ng/mL, the outcomes were also highly correlated in all PSA level ranges (r = 0.9619, 0.8094, 0.9167, and 0.9081, respectively). CONCLUSIONS: The PSA values of the Tandem-R and Abbott AxSYM assays are highly correlated in the PSA level ranges of 0.0 to less than 2.5, 2.5 to less than 4.0, 4.0 to less than 10.0, and 10.0 to less than 25.0 ng/mL.     

Genetics of cardio-vascular complications of diabetes

In this study, we investigated the immunoreactivity of the Technicon Immuno 1 PSA assay, a monoclonal-polyclonal sandwich immunoassay, with free and ACT-complexed PSA. Assay calibrators prepared with free PSA (standard Immuno 1 calibrators) and calibrators consisting of 90% ACT-complexed and 10% free PSA (90:10 calibrators) yielded virtually identical PSA recoveries at all concentrations tested. Concentrations of total PSA at approximately 4 and 10 ng/mL, prepared in varying ratios of free PSA to PSA-ACT complex, recovered from 92-104% at 4 ng/mL and from 98-102% at 10 ng/mL. Additionally, an excellent correlation of serum total PSA values from a panel of 40 prostatic cancer patient samples was obtained using calibration curves generated with the standard Immuno 1 calibrators or the 90:10 calibrators. These results demonstrate that the Technicon Immuno 1 PSA assay measures free and ACT-complexed PSA on an equal molar basis.     

Improvement of specificity in PSA-based screening by using PSA-transition zone density and percent free PSA in addition to total PSA levels

BACKGROUND: The clinical value of prostate-specific antigen (PSA) density in differentiating between prostate cancer and benign prostatic hyperplasia has been the subject of several studies. In this context the question has been raised about the diagnostic benefit of PSA transition-zone density (PSA-TZ density = total PSA/transition-zone volume) in the detection of prostate cancer. In the following study the value of PSA-TZ density alone and in combination with free PSA was investigated. METHODS: Between August 1995-May 1996, 308 first-line screening volunteers with elevated total PSA levels ranging from 2.5-10.0 ng/ml were evaluated. All patients underwent digital rectal examination, transrectal ultrasound, and transrectal ultrasound-guided biopsy of the prostate. Prior to these investigations, serum was obtained and total as well as free PSA levels were obtained. PSA transition-zone density (PSA-TZ density) was defined as follows: PSA-TZ density = total PSA/transition-zone volume. RESULTS: ROC curve analyses for PSA-TZ density showed that by using a PSA-TZ density of more than 0.22 ng/ml/cc as a biopsy criterion, 24.4% of negative biopsies could be avoided; ROC curve analyses for free PSA showed that by using percent free PSA <20% as a biopsy criterion, 45.5% of negative biopsies could be eliminated. When combining these two diagnostic tests, 54.2% of negative biopsies could be avoided. CONCLUSIONS: We conclude that PSA-TZ density, in addition to total and free PSA, is a new opportunity which renders it possible to calculate the likelihood of detecting prostate cancer on repeat biopsies in an individual patient.     

Effect of finasteride on the percentage of free PSA: implications in the early diagnosis of prostatic cancer

OBJECTIVE: To analyze the behaviour of free PSA percentage in finasteride-treated patients and to evaluate whether this ratio allows an increased PSA specificity in the early diagnosis of prostate cancer. MATERIAL AND METHODS: Evaluation of PSA serum levels and free PSA ratio in 336 patients initially diagnosed with prostate benign hyperplasia (PBH). A group of 82 patients were treated with finasteride for 14 to 58 months. A second group of 254 patients received no treatment. All patients were within the same age range and had similar PSA serum levels. In total, 141 prostate biopsies were performed: 19.5 (16/82) and 49.1 (125/254) respectively. RESULTS: Median PSA level in PBH patients was 1.6 ng/mL for the finasteride-treated group and 3.5 for the untreated group, p < 0.0001. Free PSA ratio was 18.6 and 18.8%, respectively, p > 0.05. Carcinoma detection rate was 25% (4/16) for the finasteride group and 27.2% (34/125) for the untreated group. If biopsy had been requested when PSA percentage was below 25%, 17.7 and 19.8% respectively would have been prevented and all carcinoma detected. CONCLUSION: Long-term treatment with finasteride reduces PSA serum concentration about 50% without changing the free PSA ratio. Carcinoma detection rate was similar in finasteride-treated and untreated patients. Free PSA ratio allows to increase PSA specificity and avoid unnecessary biopsied also in finasteride-treated patients.     

Transfected glucocorticoid receptor and certain GR fragments evoke cell death in malignant lymphoid, not myeloid cell lines

We compared the data from four growth hormone (GH) immunoassays for analyzing 24-h GH profiles in four apparently normal subjects and four obese subjects (508 serum samples). The detection limit was 0.02 microgram/L for one immunochemiluminometric assay (ICMA), 0.1 microgram/L for two IRMAs, and 0.4 microgram/L for one RIA. All GH pulses with a peak ICMA value > 1 microgram/L were detected by each of the other methods. Overall, the correlation coefficient between the values obtained with all four assays exceeded 0.90. However, for GH concentrations < or = 0.25 microgram/L, acceptable concordance (r2 > or = 0.80) was reached only between the ICMA and one IRMA; between the ICMA and the RIA, concordance was acceptable only for GH concentrations > or = 10 micrograms/L. In the normal subjects, the percentage of undetectable values was 0% with the ICMA but 29% with one of the IRMAs; in obese subjects, the corresponding values were 12% and 38%.     

Single-agent paclitaxel in patients with previously untreated stage IV epithelial ovarian cancer. London Gynaecological Oncology and North Thames Gynaecological Oncology Groups

OBJECTIVES: Prostate-specific antigen (PSA) is a widely used serum marker for human prostate cancer (PCa). The majority of PSA in serum is present as a complex with alpha-1-antichymotrypsin (ACT). In recent years, the ratio of free (uncomplexed) to total PSA has shown improved discrimination of PCa from benign prostatic hyperplasia. This study examines the nature of the free PSA from detected in PCa serum and shows that some of the uncomplexed PSA is an inactive precursor of PSA (pPSA). METHODS: Western blot analysis was used to detect clipped, fragment forms of PSA in sera and seminal fluid. Hydrophobic interaction chromatography-high performance liquid chromatography (HIC-HPLC) was used to identify forms of PSA present in the free PSA population. Pooled sera was passed over a PSA immunoaffinity column, and the eluted PSA components were further resolved by HIC-HPLC. RESULTS: Western blot analysis of whole sera showed complexed PSA and the intact, approximately 34 kilodalton free PSA. Only negligible levels of clipped or degraded forms of PSA, as found in seminal fluid, were detected. Column fractions measured for uncomplexed PSA using the Tandem-MP free PSA assay showed that about 25% of the free PSA eluted as pPSA beginning at the [-4]amino acid. Studies with purified recombinant [-4]pPSA showed that this proenzyme form is inactive and does not complex with ACT. CONCLUSIONS: These results suggest that the uncomplexed PSA in PCa serum is primarily unclipped PSA that contains a significant fraction of pPSA.     

Free-to-total prostate specific antigen ratio as a single test for detection of significant stage T1c prostate cancer

PURPOSE: We investigated whether impalpable, invisible (stage T1c) but significant prostate cancer can be detected better by determining the free-to-total prostate specific antigen (PSA) ratio of equivocal PSA serum levels. MATERIALS AND METHODS: The specificity of free-to-total PSA ratio using research monoclonal enzyme immunoassays was compared to that of PSA greater than 4.0 ng./ml. in 117 consecutive patients with PSA 3 to 15 ng./ml. (Hybritech Tandem-R assay) due to untreated benign prostatic hypertrophy or prostate cancer. Of the patients 77% underwent adenectomy or radical prostatectomy with thorough pathological evaluation of surgical specimens. RESULTS: Benign prostatic hypertrophy had a greater median free-to-total PSA ratio than stages T1c and T2 or greater prostate cancer (0.16 versus 0.09 and 0.11 ng./ml., p = 0.0001 and p = 0.0268, respectively). In stage T1c prostate cancer, areas under receiver operating characteristic curves were 0.58 and 0.84 for PSA and free-to-toal PSA ratio, and free-to-total PSA ratio correlated with prostate volume (r = 0.49, p = 0.005) and Gleason score (r = -0.37, p = 0.036). Pathologically, 84% of stage T1c cancers were significant and comparable to stage T2 or greater cancers. CONCLUSIONS: Free-to-total PSA ratio enhances the efficacy of PSA measurement by improving specificity for detecting impalpable, invisible but significant stage T1c prostate cancer.     

Effects of imipramine on raphe nuclei and prefrontal cortex extracellular serotonin levels in the rat

In healthy boys, the pituitary-gonadal axis exhibits diurnal variation in early puberty. Serum testosterone levels are higher during the night and low or immeasurable during the day. These fluctuating levels of circulating androgens in early pubertal boys are difficult to monitor. Prostate specific antigen (PSA) is a marker of the androgen-dependent prostatic epithelial cell activity and it is used in the diagnosis and surveillance of adult patients with prostatic cancer. We have measured PSA concentrations in serum from boys with precocious puberty before and during gonadal suppression with GnRH agonists to evaluate the effect of normal and precocious puberty on PSA levels and to study the correlation between testosterone and PSA in boys. METHODS: PSA was measured by an ultrasensitive immunofluorometric assay with a detection limit of 0.03 microgram/l. Testosterone was measured by an RIA with a sensitivity of 0.23 nmol/l, and sex hormone binding globulin was measured by a time-resolved immunofluorescence assay (sensitivity 0.23 nmol/l). Five boys with central precocious puberty (CPP) were studied before and after 12 months of GnRH agonist treatment. Sixty healthy boys (12 in each Tanner stage of puberty) and 37 healthy young males served as controls. RESULTS: PSA levels were immeasurable in all prepubertal boys, whereas PSA levels increased with increasing stage of pubertal maturation. There was a significant correlation between PSA and testosterone and free androgen indices (r = 0.61 and r = 0.65 respectively, both P < 0.001). All 5 boys with CPP had significantly elevated PSA levels which decreased to very low or immeasurable levels after GnRH agonist treatment. CONCLUSION: PSA may be a useful marker of testosterone activity in boys with normal or precocious puberty.     

Prostate-specific antigen and its complexes with alpha 1-antichymotrypsin in the plasma of patients with prostatic disease

OBJECTIVE: To improve the specificity and sensitivity of the prostate-specific-antigen (PSA) assay for the distinction between prostate cancer and benign prostate hyperplasia (BPH). METHODS: Two sensitive immunoassays, one that measures free PSA and PSA complexed to alpha 1-antichymotrypsin (alpha 1-ACT) with the same efficiency (PSAag assay) and another that specifically measures the complex between PSA and alpha 1-ACT, have been designed to measure the PSA forms in the plasma of 84 patients with prostate disease and in the seminal plasma from 60 healthy individuals. RESULTS: The proportion of plasma PSA in complex with alpha 1-ACT was significantly higher in the 34 patients with prostate cancer (89 +/- 12%, mean +/- SD; median, 91%) than in the 50 patients with BPH (71 +/- 12%; 73%) and did not correlate with the total amount of PSA. Normal seminal plasma (n = 60) had 2.1 +/- 0.6 mg/ml PSA, 175 +/- 62 microns/ml alpha 1-ACT and 9.6 +/- 3.4 micrograms/ml PSA: alpha 1-ACT complex. CONCLUSION: These results confirm that PSA: alpha 1-ACT may be a good marker for a differential diagnosis of carcinoma of the prostate and BPH.     

Effects of benzodiazepine agonists on punished responding in pigeons and their relationship with clinical doses in humans

We evaluated the AxSYM troponin I (cTnI) immunoassay for assisting in the detection of acute myocardial infarction (AMI). At four sites, the total imprecision (CV) over 20 days was 6.3-10.2%. The minimum detectable concentration was 0.14 +/- 0.05 microgram/L. Comparison of cTnI measurements between the AxSYM and Stratus (n = 406) over the dynamic range of the AxSYM assay demonstrated good correlation, r = 0.881, with a proportional bias: AxSYM cTnI = 3.50(Stratus cTnI) - 1. 10. The confidence intervals (95%) for the slope and intercept were 3.39-3.64 and -1.32 to -0.95, respectively. The expected cTnI concentration in healthy individuals was /=96%, in skeletal muscle injury, chronic renal disease, and same-day noncardiac surgery patients.     

Morphological correlates of neural regeneration in the feeding system of Aplysia californica after central nervous system lesions

Specific direct bradykinin (BK) binding and competitive inhibition was detected in human neutrophil and peripheral blood mononuclear cell (PBMC) detergent solubilized extracts and purified plasma membranes using in vitro radioreceptor ligand binding. Scatchard analyses of [125I]-BK binding revealed an equilibrium dissociation constant (Kd) of 2.9 x 10(-11) M for neutrophils and 5.6 x 10(-11) M for PBMC using [des-arg9]-BK a B1 agonist; 2.6 x 10(-11) M for neutrophils, 6.2 x 10(-11) M for PBMC with BK a B2 agonist; 5.4 x 10(-11) M for PBMC using Lys-BK a B2 agonist. The number of binding sites (Bmax) was calculated to be 0.113 fM/microgram protein (720 receptors per cell) for neutrophils and 0.200 fM/microgram protein (1289 receptors per cell) for PBMC with the B1 agonist while with the B2 agonists the values were 0.128 fM/microgram protein (818 receptors per cell) for neutrophils and 0.157 fM/microgram protein (1005 receptors per cell) for PBMC with BK, and 0.293 fM/microgram protein (1870 receptors per cell) with Lys-BK for PBMC. In a competitive binding inhibition assay using neutrophil and PBMC glycerol purified plasma membranes, high affinity binding in the nanomolar range was detected to Lys-BK and BK but with [des-arg9]-BK a 10-100 fold lower order affinity was observed this being indicative of pharmacologically defined B2 characteristics.     

Determination of free follistatin levels in sera of normal subjects and patients with various diseases

We developed an assay system for measuring free follistatin by using an anti-follistatin mouse monoclonal antibody and [125I]activin A. The sensitivity of this assay was 0.5 microgram/l and cross-reactivities with inhibin, luteinizing hormone, follicle-stimulating hormone and growth hormone were all less than 0.5%. The dose-response curves of human sera and follicular fluid were parallel to the standard curve, and the follicular fluid contained a large amount of follistatin (6.4 +/- 0.5 mg/l, mean +/- SEM; N = 13). The within- and between-assay coefficients of variation calculated from the analysis of serum samples of four different concentrations were 3.3-7.8% and 3.9-11.0%, respectively. The recovery rates of free follistatin at five different doses were 86.4 - 102.4%. When activin A was added to the same sample, free follistatin recovery rate declined dose-dependently. Gel filtration analyses of human serum and follicular fluid resulted in a single peak corresponding to authentic follistatin. Using this assay, free follistatin concentrations in sera were measured in normal, pregnant and diseased subjects. The free follistatin level in serum of normal adults was 3.5 +/- 0.2 micrograms/l (N = 60), which was significantly elevated in pregnant women (16.7 +/- 1.3 micrograms/l, N = 56), and in patients with chronic liver disease (8.1 +/- 1.1 micrograms/l, N = 20), chronic renal failure (6.7 +/- 0.9 micrograms/l, N = 42), advanced solid cancer (8.5 +/- 1.0 micrograms/l, N = 39) and hematological malignancies (6.8 +/- 1.0 micrograms/l, N = 18). These data indicated that the free follistatin concentration in serum is detectable and varies during pregnancy and in various diseased states.     

Isolation and characterization of free form prostate specific antigen (f-PSA) in sera of men with prostate cancer

PURPOSE: The free uncomplexed form of prostate specific antigen (f-PSA) from prostate cancer sera was partially isolated and characterized because the molecular form of f-PSA in the serum is unknown. MATERIALS AND METHODS: 230 ml. of sera from 59 men with bone metastasis and individual PSA values of >2000 ng./mL were combined and centrifuged for 60 minutes at 30,000 RPM (4C). The sera were fractionated by gel filtration column chromatography (Sephacryl S-200, 2.5 cm. x 92 cm.). Free and complexed PSA in the eluted fractions were isolated by measuring immunoreactivity of PSA (Tosoh AIA-600 assay); f-PSA from 23 separate runs were combined, concentrated and re-chromatographed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to immobilize the isolated proteins onto a nitrocellulose membrane and a polyvinylidene difluoride (PVDF) membrane. Monoclonal antibody (F5) was used to probe PSA on nitrocellulose membrane and the PSA band was detected by Emission Chemoluminescence (ECL) kit. Amino terminal sequence analysis of the isolated f-PSA was performed with a gas-phase sequentor (Applied Biosyntens 4760 A) using the program designed by the manufacturer. RESULTS: 0.5 cc of f-PSA (27,000 ng./mL) was obtained from serums after rechromatography. SDS-PAGE showed one double band around 30 kDa; with ECL technique, one major band at 30-kDa was identified as PSA. The amino terminal sequence analysis of this band showed residue 1 through 9 and 146 through 152. CONCLUSIONS: In our preliminary experiment, the free form of serum PSA is partially isolated directly from human sera. Amino terminal sequence analysis has shown that serum f-PSA is not a pre-mature or zymogen form of PSA because serum f-PSA has a N-terminus identical to that of seminal fluid PSA. A nicked form of f-PSA is also found in these patient sera.     

Free-to-total prostate-specific antigen (PSA) ratio improves the specificity for detecting prostate cancer in patients with prostatism and intermediate PSA levels

OBJECTIVE: To investigate the clinical significance of the free-to-total prostate-specific antigen (PSA) ratio in improving the specificity of PSA measurement for detecting prostate cancer within the diagnostic intermediate range (4-10 ng/mL total PSA) in patients referred for the treatment of urinary symptoms. PATIENTS AND METHODS: Serum samples were obtained from 333 consecutive patients with obstructive and irritative urinary symptoms. Of these men, 114 had total PSA levels of 4-10 ng/mL; 22 had prostate cancer (group 1) and 71 had benign prostatic hyperplasia (BPH, group 2). Group 3 consisted of 21 patients with BPH and a chronic indwelling catheter. The concentrations of free and total PSA (ProStatus, Wallac Oy, Turku, Finland) and PSA complexed to alpha-1-antichymotrypsin were measured and the free-to-total PSA ratio calculated. All patients under 70 years of age or with suspicious findings on digital rectal examination or transrectal ultrasonography underwent ultrasound-guided sextant prostate biopsies. Of the 114 patients, 105 (92%) underwent transurethral resection of the prostate and six (5%) radical retropubic prostatectomy. RESULTS: Patients in group 1 had significantly lower median free PSA concentrations (0.78 ng/mL vs 1.13 ng/mL, P < 0.001) and a lower free-to-total PSA ratio (12.1% vs 19.9%, P < 0.001) than those in group 2. The differences were similar between group 1 and group 3 (median free PSA in group 3, 1.06 ng/mL, P = 0.03, and free-to-total PSA ratio 18.7%, P = 0.007). There were no significant differences between patients in groups 2 and 3. The free-to-total PSA ratio had a higher specificity than total PSA at all sensitivity levels, e.g. a threshold free-to-total PSA ratio of 0.20 detected 91% of cancers and spared 48% (group 2) or 46% (group 3) from unnecessary biopsies. The area under the receiver operating characteristic curve for group 1 vs group 2 was 0.56 (total PSA) and 0.78 (free-to-total PSA ratio) and for group 1 vs group 3 was 0.56 (total PSA) and 0.81 (free-to-total PSA ratio). CONCLUSION: In those patients with extensive symptoms from BPH and requiring surgical treatment, the free-to-total PSA ratio improves the specificity for detecting prostate cancer in the diagnostic 'grey zone' of 4-10 ng/mL total PSA. This improvement occurred in patients with or without a chronic indwelling catheter for urinary retention.     

The importance of human glandular kallikrein and its correlation with different prostate specific antigen serum forms in the detection of prostate carcinoma

BACKGROUND: Human glandular kallikrein (hK2), the prostate specific antigen (PSA) close homologue, possesses approximately 80% structure identity with PSA. The identification of PSA was an important step in the detection of prostate carcinoma (PCa). Thus, hK2 measurement in the serum has the potential to become another important diagnostic test for PCa. In the current study, the authors measured the serum concentrations of the hK2 with "in-house" immunofluorometric assays in different patient groups. The correlation between serum hK2 and different PSA forms was investigated. METHODS: The prospectively collected serum samples were obtained preoperatively on admission from 311 consecutive male patients. Sixteen patients did not fulfill inclusion criteria; the remaining patients were divided into four groups (Groups I-III confirmed histologically): Group I: patients with PCa (n = 56); Group II: patients with benign prostatic hyperplasia (BPH) (n = 163); Group III: patients with BPH with a chronic in-dwelling catheter (BPH cat) (n = 44); and Group IV-control group (n = 32). The patients in Group IV had urolithiasis, varicocele, or kidney or bladder tumors). An experimental immunofluorometric assay with an analytic sensitivity of 0.01 ng/mL and a functional sensitivity of 0.05 ng/mL was used to determine serum hK2 concentrations. Total PSA, free PSA, and PSA complexed to alpha-1-antichymotrypsin (PSA-ACT) also were measured. hK2 concentrations equal to or above the functional sensitivity limit were correlated with each of these PSA serum forms. Free to total PSA, hK2 to total PSA, and hK2 to free PSA ratios were calculated and compared in different patient groups. RESULTS: The hK2 concentrations were equal to or above the functional sensitivity limit in 179 of 311 samples (57.6%). In these samples, hK2 correlated best with free PSA (correlation coefficient [r] = 0.79) and correlated well with total PSA (r = 0.72) and PSA-ACT (r = 0.74). Similar correlations also could be observed when each clinical group was analyzed separately. The median proportion of hK2 in relation to total PSA was 2.1%, 1.8%, and 1.4%, respectively, for PCa, BPH, and BPH cat patients. Both the free to total PSA ratio and the hK2 to free PSA ratio discriminated well between PCa and BPH patients. Within the range of total PSA of 4-10 ng/mL (PCa [n = 11] and BPH [n = 41]) the hK2 to free PSA ratio had a specificity of 63.4% and 90.9% sensitivity (area under the receiver operating characteristic [ROC] curve = 0.85) whereas the free to total PSA ratio had a 34.1% specificity at the same sensitivity level (area under ROC curve = 0.74). CONCLUSIONS: The hK2 serum level correlates well with all PSA serum forms in all clearly defined clinical groups. The preliminary finding that the hK2 to free PSA ratio appeared to improve the detection of PCa compared with the free to total PSA ratio in patients with total PSA within a 4-10 ng/mL range is of clinical interest. Combining human serine proteases in the multivariate regression analysis will be a tool to improve cancer detection. Further investigations with more sensitive hK2 assays and in larger patient populations are needed to confirm this finding.     

Does mandating continuing education mandate competence?

Serial prostate-specific antigen (PSA) measurements (PSA velocity) as an additional instrument to detect prostatic cancer was introduced in 1992. It has previously been reported that PSA increase per year differed in the last 5 years prior to diagnosis in patients with benign prostatic hyperplasia (0.18 ng/ml/year), locally confined (0.75 ng/ml/year) and metastasized (4.4 ng/ml/year) cancer of the prostate (CaP) in contrast to healthy men (0.04 ng/ml/year). The ability of PSA velocity to detect organ-confined CaP in patients with intermediate PSA serum values depends therefore on a reliable and reproducible PSA result. The present study comprised 85 men with PSA values between 3 and 8 ng/ml (Abbott IMx). PSA measurements were repeated with Abbott IMx (n = 85 patients) and Hybritech Tandem-E (n = 59 patients) assays. The PSA serum values differed from one examination to the other from 0.02 to 2.74 ng/ml with the Abbott IMx. Standard deviation amounted to 0.35 ng/ml with the Abbott IMx PSA assay. Using the Hybritech Tandem-E assay, mean standard deviation was 1.15 ng/ml and therefore higher than with the Abbott IMx assay. The difference from one test to the other ranged from 0.05 to 4.05 ng/ml with the Hybritech Tandem-E. Using the Abbott IMx assay, 10.6% of all repeat measurements exceeded 1 ng/ml whereas in the Hybritech Tandem-E assay 62.7% of the second measurements differed > 1 ng/ml from the first PSA result. An increase in PSA serum values may therefore be due to intratest variation, physiological day-to-day variation as well as prostatic disease. It is important to notice that the intra-assay variation may be greater than the PSA increase per year in a patient with CaP. Therefore, PSA velocity seems to be of limited value.