The patient's perception of having recovered from an eating disorder.

Our aim in this study was to describe how patients perceive having recovered from eating disorders. A qualitative method with a phenomenographic approach was used to identify various ways of experiencing recovery. Four categories emerged, describing how the subjects now relate in a relaxed and accepting manner to food, the body, themselves as individuals, and their social environment. Some perceived recovery as coping with emotions, while others experienced themselves as healthier than people in general regarding food and weight. Different aspects were emphasized as important for recovery. As long as patients perceive themselves as recovered, it is not necessary that they fulfill all conceivable criteria for recovery.

Reasons for non-participation in follow-up research on eating disorders.

OBJECTIVE: Lack of participation in follow-ups is thought to be a serious bias in outcome research on eating disorders; however, little systematic knowledge exists about the problem. The present study aimed to delineate non-participation in long-term follow-up research, and explore the reasons for non-participation. METHOD: Eating disorder patients (N=840) entering a naturalistic, longitudinal multi-centre study were divided into participators (N=508) and non-participators (N=332) in 36-month follow-ups. Non-participators were further classified as either active (i.e. refused participation or failed to attend scheduled appointments) or passive non-participators (i.e. could not be traced). RESULTS: Active non-participators exhibited significantly lower levels of general and eating disorder psychopathology at intake compared to participators, while passive non-participators reported higher levels of hostility. DISCUSSION: Systematic exploration of non-participation in longitudinal research can help to mitigate the problem of indistinct results due to missing data. Barriers to successful longitudinal research and how to overcome non-participation at endpoint are discussed.

Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types.

PURPOSE: To establish the safety and tolerability of ZD1839 (Iressa), a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, and to explore its pharmacokinetic and pharmacodynamic effects in patients with selected solid tumor types. PATIENTS AND METHODS: This was a phase I dose-escalating trial of oral ZD1839 150 mg/d to a maximum of 1,000 mg/d given once daily for at least 28 days. Patients with either advanced non-small-cell lung, ovarian, head and neck, prostate, or colorectal cancer were recruited. RESULTS: Eighty-eight patients received ZD1839 (150 to 1,000 mg/d). At 1,000 mg/d, five of 12 patients experienced dose-limiting toxicity (grade 3 diarrhea [four patients] and grade 3 somnolence [one patient]). The most frequent drug-related adverse events (AEs) were acne-like rash (64%) and diarrhea (47%), which were generally mild (grade 1/2) and reversible on cessation of treatment. No change in ZD1839 safety profile was observed with prolonged administration. Pharmacokinetic analysis showed steady-state exposure to ZD1839 in 98% of patients by day 7. Nineteen patients had stable disease and received ZD1839 for >or= 3 months; seven of these patients remained on study drug for >or= 6 months. Serial skin biopsies taken before treatment and at approximately day 28 revealed changes indicative of inhibition of the EGFR signaling pathway. CONCLUSION: ZD1839 was generally well tolerated, with manageable and reversible AEs at doses up to 600 mg/d and dose-limiting toxicity observed at 1,000 mg/d. ZD1839 treatment resulted in clinically meaningful disease stabilization across a range of tumor types and doses. Pharmacodynamic changes in skin confirmed inhibition of EGFR signaling, which was predicted from the mode of action of ZD1839.

Lipoxin formation in human nasal polyps and bronchial tissue.

Chopped human nasal polyps and bronchial tissue produced lipoxin A4 and isomers of lipoxins A4 and B4, but not lipoxin B4, after incubation with exogenous leukotriene A4. In addition, these tissues transformed arachidonic acid to 15-hydroxyeicosatetraenoic acid. The capacity per gram of tissue to produce lipoxins and 15-hydroxyeicosatetraenoic acid was 3-5-times higher in the nasal polyps. Neither tissue produced detectable levels of lipoxins or leukotrienes after incubation with ionophore A23187 and arachidonic acid. Co-incubation of nasal polyps and polymorphonuclear granulocytes with ionophore A23187 led to the formation of lipoxins, including lipoxins A4 and B4. The results indicate the involvement of an epithelial 15-lipoxygenase in lipoxin formation in human airways.

Production of alpha-1-antichymotrypsin by PSA-containing cells of human prostate epithelium.

Prostate-specific antigen (PSA) is a chymotrypsin-like serine protease exclusively produced by the prostate epithelium, and abundant in seminal fluid. In serum, PSA is predominantly complexed to a liver-derived serine protease inhibitor, alpha-1-antichymotrypsin (ACT). A higher proportion of serum PSA is complexed to ACT in prostate cancer than in benign prostate hyperplasia. Since the molecular basis for this is unclear, we have investigated whether or not ACT may be produced in the prostate gland. Immunocytochemistry, using either monoclonal or polyclonal IgGs, demonstrated specific immunostaining for ACT in normal PSA-containing prostate epithelium. Production of ACT in the normal PSA-producing prostate epithelium was demonstrated by means of nonradioactive in situ hybridization using 30-mer anti-sense DNA probes for ACT and for PSA. The ACT and PSA coding transcripts, as detected by in situ hybridization, were distributed perinuclearly, in contrast to the specific immunostaining for ACT and PSA which was most intense in the apical portion of the secretory cells. The results strongly suggest local production and release of ACT by the normal prostate epithelium that may be important for interaction between PSA and ACT in extracellular compartments.

Alpha 1-antichymotrypsin production in PSA-producing cells is common in prostate cancer but rare in benign prostatic hyperplasia.

OBJECTIVE: To investigate the distribution and production of alpha 1-antichymotrypsin (ACT) and prostate-specific antigen (PSA) in benign hyperplastic and malignant prostatic tissue, respectively. METHODS: Using monoclonal anti-ACT and anti-PSA IgGs for immunocytochemistry and alkaline phosphatase conjugated 30-mer oligodeoxynucleotide probes for nonradioactive in situ hybridization, tissue specimens were studied from 15 patients with benign prostatic hyperplasia after transurethral resection of the prostate (TURP) and from 9 patients with bladder cancer who underwent cystoprostatectomy. Cancer specimens were from 23 TURP patients and from ultrasound guided core biopsies in 14 patients. Prostate tumors were graded according to the Gleason system. RESULTS: We found no or only occasional small foci of immunostaining for ACT, and no ACT transcripts in the PSA-producing epithelium in areas with benign nodular hyperplasia. By contrast, a high proportion of cells expressed both ACT and PSA in prostate cancers with low Gleason score, as detected by immunocytochemistry and in situ hybridization. Poorly differentiated tumor cells manifested greater variation in immunostaining for both ACT and PSA. As compared to tumors of low Gleason score, high-score tumors less frequently manifested immunostaining for ACT than for PSA, and less frequently generated hybridization signals for both PSA and ACT transcripts. CONCLUSIONS: A significantly higher proportion of serum PSA has been reported to be complexed to ACT in patients with prostate cancer than in patients with benign prostatic hyperplasia. The presently reported lack of ACT production in PSA-containing BPH nodules may contribute to this by making conditions less optimal for complex formation between PSA and ACT. As opposed to this, production of both ACT and PSA in prostate cancers may enhance the complex formation between PSA and ACT.

Rapid exponential elimination of free prostate-specific antigen contrasts the slow, capacity-limited elimination of PSA complexed to alpha 1-antichymotrypsin from serum.

OBJECTIVES: To study the rates of elimination of total prostate-specific antigen (PSA-T), free PSA (PSA-F), and PSA complexed to alpha 1-antichymotrypsin (PSA-ACT) from blood after radical retropubic prostatectomy (RRP). METHODS: We obtained venous blood from 10 patients with prostate cancer who were undergoing RRP. We analyzed PSA-F and PSA-ACT and equimolar detection of both of these forms together (PSA-T) by using immunofluorometric assays. An attempt was made to fit the serum concentrations of PSA-F, PSA-ACT, and PSA-T for each patient to exponential curves by applying one- and two-compartment models for pharmacokinetic analysis. RESULTS: Manipulation of the prostate during RRP resulted in a 3- to 28-fold increase in PSA-F concentrations in serum. Removal of the prostate resulted in a rapid, biexponential elimination of PSA-F from serum, corresponding to a mean initial (alpha) half-life of 0.81 hours and a mean terminal (beta) half-life of 13.9 hours. Serum PSA-ACT concentrations decreased by 20% to 40% immediately after removal of the gland; the elimination after surgery was slow and nonexponential, corresponding to a mean rate of 0.8 ng/mL/day. The elimination of PSA-T reflects a combination of the elimination patterns for PSA-F and PSA-ACT. CONCLUSIONS: The main proportion of PSA-F is rapidly eliminated from serum, possibly by glomerular filtration. PSA-F released during surgery did not form complexes with ACT, as suggested by the lack of PSA-ACT elevation in serum. The size (approximately 90 kDa) and the extensive in vitro stability of the PSA-ACT complex prevents renal clearance. The nonexponential elimination of the PSA-ACT complex is evidence of a capacity-limited process (e.g., metabolic transformation).

Comparison of analysis of the different prostate-specific antigen forms in serum for detection of clinically localized prostate cancer.

OBJECTIVES: To compare different forms and ratios of serum prostate-specific antigen (PSA) to determine which form or ratio provides optimal diagnostic specificity and sensitivity in distinguishing between benign prostatic hyperplasia (BPH) and clinically localized prostate cancer. METHODS: Serum samples were obtained from 47 patients with BPH and 39 with clinically localized prostate cancer. Patients with BPH underwent either transurethral resection of the prostate or transurethral microwave thermotherapy. Patients with prostate cancer, all of whom had no metastases on radionucleotide bone scans and no pelvic lymph node involvement, underwent either radical external beam radiation therapy or radical retropubic prostatectomy. All patients had pretreatment serum PSA levels between 1 and 20 ng/mL. The different forms of serum PSA (free PSA [PSA-F], PSA complexed to alpha 1-antichymotrypsin [PSA-ACT], and total PSA [PSA-T]) were measured using different monoclonal antibodies against PSA and ACT and immunofluorometric assay techniques. Furthermore, three ratios (PSA-F/PSA-T, PSA-ACT/PSA-T, and PSA-F/PSA-ACT) were calculated. RESULTS: By receiver operating characteristic curve analysis, the performance of the different forms and ratios were compared. The PSA-F/PSA-T ratio had the greatest area under the curve (AUC, 0.776), significantly larger than that for PSA-T (0.612; P = 0.024). For PSA-ACT/PSA-T, the AUC was 0.695 (P = 0.283 versus PSA-T) and 0.773 for PSA-F/PSA-ACT (P = 0.051 versus PSA-T). At a cutoff level < 0.17, PSA-F/PSA-T had a sensitivity of 79%, a specificity of 66%, and a positive predictive value of 66% compared with 74%, 38%, and 50%, respectively, for PSA-T at a cutoff level > 4.0 ng/mL. CONCLUSIONS: The PSA-F/PSA-T ratio gives the best diagnostic performance compared with that for other forms and ratios of PSA and will reduce the number of prostatic biopsies in patients with BPH.

The prognostic value of different forms of prostate specific antigen and their ratios in patients with prostate cancer.

OBJECTIVE: To assess the prognostic value for patient survival of different forms of PSA and ratios thereof, before treatment for prostate cancer, by considering the forms and ratios both as independent markers and by comparing them with other commonly used prognostic markers, e.g. tumour grade, local stage (T-stage) and absence or presence of skeletal metastases (M-stage). PATIENTS AND METHODS: Blood samples were collected consecutively from men diagnosed with prostate cancer at our department in 1988. From this group, 66 men were followed until death, or for >/=9 years. Twenty-five patients died from their prostate cancer and 21 from other causes during the follow-up period. Forty-eight patients received hormonal treatment, whereas 18 remained untreated or received no treatment for their cancer before they died from other causes. Assays measuring the serum levels of free prostate specific antigen (fPSA), PSA complexed to alpha1-antichymotrypsin (PSA-ACT), and total PSA (tPSA) were used to calculate the percentage of free to total PSA (f/tPSA) fPSA/ACT and ACT/tPSA at diagnosis. Based on the initial levels or ratios of the PSA forms, the patients were divided into three numerically comparable groups (tertiles) for survival analysis. Prognostic factors predicting patient survival were evaluated using univariate (Kaplan-Meier life-tables with the log-rank test) and multivariate techniques (Cox proportional hazards regression model). RESULTS: Univariate analysis using the log-rank test showed that the serum level of each molecular form of PSA, i.e. tPSA (P=0.001), PSA-ACT (P<0.001) and fPSA (P<0.001), as well as grade (P<0.001), T-stage (P=0.00355) and M-stage (P<0.001), provided statistically significant prognostic information. Log-rank tests showed that none of the ratios, i.e. f/tPSA, fPSA/ACT and ACT/tPSA, were informative of prognosis (P>0.05). However, in a multivariate analysis regression model, not only M-stage (risk ratio 4.2; P=0. 026) and grade (risk ratio 2.6; P=0.022), but also f/tPSA (risk ratio 1.8; P=0.037), provided significant prognostic information. CONCLUSION: The values of tPSA, fPSA and PSA-ACT, as well as grade and T- and M-stage, are all independent prognostic factors of prostate cancer survival. In a multivariate analysis, not only M-stage and grade but also f/tPSA provided significant prognostic information.

Controlled trial of a short and a prolonged course with ciprofloxacin in patients undergoing transurethral prostatic surgery.

The efficacy of a short (Group I) and a prolonged (Group II) course with ciprofloxacin was assessed in patients undergoing transurethral prostatic resection for benign hyperplasia or cancer of the prostate and compared with that of controls without antibiotic (Group III). Both regiments significantly reduced the frequency of postoperative bacteriuria (p less than 0.01) and of severe infectious complications (p = 0.004) as compared to the controls. Both regimens were equally effective in preventing perioperative and postoperative acquisition of bacteriuria in patients without bacteriuria at surgery. In patients with bacteriuria before surgery, bacteriuria was found postoperatively in 35% in Group I and 10% in Group II (p = 0.012), but in 82% of the patients in Group III. Ciprofloxacin inhibited all but 7 of 176 bacterial strains at an MIC of less than or equal to 1 microgram/ml. Given orally ciprofloxacin is a valuable alternative antimicrobial for use in conjunction with transurethral prostatic resection. A short course is sufficient for prophylaxis, and adequate therapy is achieved with a prolonged regimen.

Quantitative bone scintigraphy in patients with prostatic carcinoma treated with LH-RH analogues.

In 14 men with prostatic carcinoma, quantitative scintigraphy of the vertebrae from Th10 to L5 was performed before and 2 weeks and 2 and 6 months after start of treatment with luteinizing hormone-releasing hormone (LH-RH) analogues. Serum prostate-specific antigen (PSA) was also determined. The patients with normal bone scintigram showed no change in gamma camera count rate during the study, but fall in PSA values. The patients with abnormal bone scintigram responded to treatment with flare phenomenon, with increased count rate at 2 weeks, followed by fall to pretreatment level at 2 months. PSA showed decrease as early as 2 weeks after the start of treatment. Bone scintigraphy was found to be useful before therapy, especially in patients with elevated PSA levels, and after 2 months, when the flare phenomenon had subsided. Serial measurement of PSA provided a guide to disease activity.

Use of ciprofloxacin in patients undergoing transurethral prostatic surgery.

The efficacy of a short (Group I) and a prolonged (Group II) course with ciprofloxacin was assessed in patients undergoing transurethral prostatic resection and compared with that of controls without antibiotic (Group III). Both regimens significantly reduced the frequency of post-operative bacteriuria (p less than 0.01) and of severe infectious complications (p = 0.004) compared to the controls. Both regimens were equally effective in preventing peri-operative and post-operative acquisition of bacteriuria in patients without bacteriuria at surgery. In patients with bacteriuria before surgery, bacteriuria was found post-operatively in 35% in Group I and in 9% in Group II (p = 0.012), but in 82% of the patients in Group III. Ciprofloxacin inhibited all but 7 of 176 bacterial strains at an MIC of less than or equal to 1 microgram/ml. Given orally, ciprofloxacin is a valuable alternative antimicrobial for use in conjunction with transurethral prostatic resection. A short course is sufficient for prophylaxis, and adequate therapy is achieved with a prolonged regimen.

Dual-label one-step immunoassay for simultaneous measurement of free and total prostate-specific antigen concentrations and ratios in serum.

We developed a simple one-step dual-label immunoassay for simultaneous measurement of the free, noncomplexed form of prostate-specific antigen (PSA) and total PSA. The assay is based on time-resolved fluorescence and includes a stable fluorescent chelate of Eu to label a monoclonal antibody (mAb) that detects only free PSA, whereas a second mAb labeled with a fluorescent chelate of Tb provides equimolar detection of both free PSA and PSA complexed to alpha 1-antichymotrypsin. A third mAb on a solid phase captures the free and complexed forms of PSA in an equimolar fashion. The simultaneous measurement of the free-to-total PSA ratio (F/T) with the one-step dual assay is not sensitive to variations in the sample volume. The discrimination between benign prostatic hyperplasia and prostate cancer patients, i.e., the area under the receiver-operating characteristic curve, increased from 0.64 (total PSA assay) to 0.78 and 0.81 when the F/T ratio was measured with single and dual assays, respectively.

Similar rates of exponential decrease in serum concentrations of free prostate-specific antigen (PSA), PSA complexed to alpha-1-antichymotrypsin, and human glandular kallikrein 2 (hK2) in prostate cancer patients treated with GnRH-analogues.

BACKGROUND: Our recently reported finding of rapid bi-exponential elimination of free prostate-specific antigen (PSA) after radical retropubic prostatectomy in patients with moderately elevated PSA levels, which contrasted a very slow, linear elimination of PSA complexed to alpha-1-antichymotrypsin (ACT), prompted us to study whether these elimination rates were applicable for patients selected for castration treatment with very high pretreatment concentrations of PSA in serum. In addition, serum concentrations of hK2, the activator of proPSA, were measured. METHODS: Pretreatment serum was obtained from 21 previously untreated prostate cancer patients due for hormonal treatment with a GnRH-analog. Samples were also collected during treatment up to a minimum of 24 weeks at 2-week intervals and analyzed with immunofluorometric assays for free PSA (PSA-F), PSA complexed to alpha-1-antichymotrypsin (PSA-ACT), total PSA (PSA-T), and human kallikrein 2 (hK2). For pharmaco-kinetic analysis the serum concentrations of hK2 and PSA forms for each patient were plotted against time both before and after logarithmic transformation and the half-lives were calculated as ln2/k. RESULTS: Median pretreatment serum concentrations were 322 ng/ml (range, 1.9-2210) for PSA-T, 27.8 ng/ml (range, 1.14-259) for PSA-F, and 207 ng/ml (range, 0.8-2080) for PSA-ACT. All patients had castrate levels of serum testosterone (< 2.5 nmol/l) in less than 21 days after initiation of GnRH-analog treatment. It was possible to evaluate data from 19/21 patients which showed an exponential decrease of all PSA concentrations in serum, with mean half-lives of 12.9 days (range, 7.3-30) for PSA-T, 15.5 days (range, 7.7-37.5) for PSA-F, and 12.3 days (range, 6.6-30) for PSA-ACT. Median pretreatment percent free PSA (PSA-F/PSA-T) was 12% compared to 18% at nadir. The median pretreatment level of hK2 was 3.5 ng/ml (range, 0.29-30.3). There was an exponential decrease in hK2 concentrations in serum after initiation of hormonal treatment with a mean half-life of 18.7 days (range, 7.5-37.5). CONCLUSIONS: For the majority of patients with hormonally treated prostate cancer the serum concentrations of PSA-T, PSA-F, PSA-ACT, and hK2 decreased slowly in parallel and mono-exponentially after initiation of treatment. Mean half-lives were between 12 and 19 days.

Discrimination of men with prostate cancer from those with benign disease by measurements of human glandular kallikrein 2 (HK2) in serum.

PURPOSE: To investigate the clinical value of measuring human glandular kallikrein 2 (hK2) compared with free and total prostate specific antigen (PSA-F and PSA-T) in serum from patients with prostate disease. MATERIALS AND METHODS: Serum from healthy controls, from men with benign prostate hyperplasia (BPH), clinically localized prostate cancer (PCa), and advanced PCa were analyzed for hK2 (using an in-house-research assay with detection limit of 0.05 ng./mL and <0.1% cross-reaction with PSA) and for PSA-F and PSA-T (using the Dual Prostatus assay from EG&G Wallac). RESULTS: HK2 concentrations were <0.05 ng./mL in 50/50 healthy volunteers but significantly higher (p <0.0001) and > or =0.05 ng./mL in 28/54 (52%) patients with BPH. In comparison to these men, the hK2 levels were significantly higher (p <0.0001, median 0.085 ng./mL) and > or =0.05 ng./mL in 100/136 (74%) men with clinically localized PCa. Compared with localized PCa, the hK2 levels were significantly higher (p <0.0001, median 0.57 ng./mL) and > or =0.05 ng./mL in 55/57 (96%) patients with advanced PCa. The median hK2 levels ranged from 1.3 to 1.6% of those of PSA-T in all three patient groups, whereas percent hK2/PSA-F and hK2 x PSA-T/PSA-F levels were significantly higher in cancer patients compared with those with BPH. In the discrimination of clinically localized PCa from BPH, hK2 x PSA-T/PSA-F gave the largest area under the receiver operating curve (AUC = 0.81) and significantly (p = 0.025) larger AUC than PSA-T alone (0.70). Further, at 95% sensitivity there was significant gain in specificity, and at specificity levels of 90 to 95% there was significant gain in sensitivity using the measurements of PSA-T+PSA-F+hK2 compared with analysis of PSA-T and/or percent free PSA. CONCLUSIONS: Discrimination of patients with benign prostate disease from those with prostate cancer was significantly enhanced using measurements of hK2 in addition to those of PSA-T and PSA-F. Percent hK2/PSA-F was higher in PCa than in BPH, a phenomena not yet understood.

Significance and metabolism of complexed and noncomplexed prostate specific antigen forms, and human glandular kallikrein 2 in clinically localized prostate cancer before and after radical prostatectomy.

PURPOSE: We studied plasma concentrations and elimination rates of prostate specific antigen (PSA) complexed to alpha1-antichymotrypsin and alpha2-macroglobulin, free PSA, total PSA (free PSA plus PSA alpha1-antichymotrypsin) and human glandular kallikrein 2 before, during and after radical retropubic prostatectomy for clinically localized prostate cancer. MATERIALS AND METHODS: Plasma was collected and frozen within 10 minutes after sampling from 18 patients undergoing radical retropubic prostatectomy for prostate cancer. One sample was drawn preoperatively. Subsequent sampling intervals were 5 to 20 minutes perioperatively, 2 to 4 hours during the first 12 postoperative hours and 24 to 48 hours until postoperative day 14. Free PSA, PSA alpha1-antichymotrypsin, total PSA, PSA alpha2-macroglobulin and human glandular kallikrein 2 were measured with time resolved immunofluorometric assays. RESULTS: Preoperatively PSA alpha2-macroglobulin was undetectable (less than 2 ng./ml.) in 17 of 18 patients. Human glandular kallikrein 2, free PSA and total PSA but not PSA alpha1-antichymotrypsin were significantly higher in patients with extraprostatic cancer (pT3a-pT4a, pN1) compared to those with organ confined cancer (pT2a/b). Surgical manipulation of the prostate caused no detectable elevation of human glandular kallikrein 2, PSA alpha1-antichymotrypsin or PSA alpha2-macroglobulin. In contrast, a mean 9.6-fold increase (range 3.4 to 22) in free PSA was noted 5 minutes after prostatectomy. Free PSA was eliminated from plasma in a biphasic exponential pattern with an early plasma half-life of 55 minutes and a late plasma half-life of 18 hours. PSA alpha1-antichymotrypsin decreased slowly, whereas human glandular kallikrein 2 was detectable only 12 hours after prostatectomy. PSA alpha2-macroglobulin remained at insignificant, nondetectable concentrations during the entire perioperative and postoperative period. CONCLUSIONS: Release of free PSA contributes to the elevation of plasma total PSA after prostatectomy. Free PSA is enzymatically inactive as the release does not result in subsequent elevation of PSA alpha1-antichymotrypsin or PSA alpha2-macroglobulin. Biphasic exponential elimination of free PSA may be explained by rapid extracellular redistribution (early half-life) and glomerular filtration in the kidneys (late half-life). Our data suggest rapid metabolism of human glandular kallikrein 2 but do not support suggestions of the significance in vivo of complex formations with alpha2-macroglobulin as a major means to eliminate PSA from plasma in patients with clinically localized prostate cancer.

Radioimmunoassay of beta-microseminoprotein, a prostatic-secreted protein present in sera of both men and women.

We describe a simple radioimmunoassay of beta-microseminoprotein, one of the three most abundant secretory proteins of the prostate gland. The detection limit of the assay is 1 microgram/L, and its precision, expressed as the total coefficient of variation, is less than 10% for values between 10 and 150 micrograms/L. Using this assay, we found that beta-microseminoprotein immunoreactivity was present in sera from both sexes at about the same concentration. The protein detected had the same molecular size on gel chromatography as the protein isolated from seminal plasma, and dilution curves for the sera paralleled that for the pure protein. The findings suggest that beta-microseminoprotein is present in serum of healthy subjects of both sexes and that it originates in tissue other than the prostate gland. The range of the serum concentration was 0-10.6 micrograms/L (median 4.1) for 51 healthy adult women and 1.1-14.7 micrograms/L (median 6.2) for 35 healthy adult men not older than 40 years. In males with prostatic cancer the concentration in serum was highly variable and often greatly increased. The concentration of beta-microseminoprotein was correlated with that of creatinine in serum, suggesting that the protein is eliminated--at least partly--from the circulation by glomerular filtration. Little of the protein was present in the urine of women. In urine from men the concentration was high and variable, probably because of local contribution from the prostate gland to the urethral urine.

Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer.

Prostate specific antigen (PSA) in serum has recently been shown to occur in complex with alpha 1-antichymotrypsin and as an approximately 30 kDa. noncomplexed molecular form. We characterized PSA by 3 different assays in samples from 144 patients with benign prostatic hyperplasia (BPH) and 121 with carcinoma of the prostate. One of these noncompetitive assays measured total PSA by detecting PSA complexed to serine proteinase inhibitors and the noncomplexed molecular form, a second measured only PSA in complex with alpha 1-antichymotrypsin, whereas a third detected the noncomplexed form. PSA in complex with alpha 1-antichymotrypsin was the predominant form in all patient sera. Noncomplexed PSA constituted a minor fraction that was significantly smaller in patients with untreated prostate cancer than in those with BPH (p < 0.0001). The proportion of noncomplexed PSA does not correlate to the serum concentration of PSA or that of alpha 1-antichymotrypsin. In men with a serum PSA concentration of less than 10 micrograms./l. the combination of assays measuring total PSA immunoreactivity, the noncomplexed molecular form and PSA in complex with alpha 1-antichymotrypsin may facilitate discrimination between prostate cancer and BPH.