Variation of free and total prostate-specific antigen levels: the effect on the percent free/total prostate-specific antigen.

OBJECTIVE: Recent studies have shown that calculations of the percent free/total prostate-specific antigen (PSA) improves the specificity of PSA testing. Characterizing the variability of free PSA and total PSA is necessary to evaluate the utility of an isolated free/total PSA measurement. We investigated the total variation of free and total PSA levels to determine how the percent free/total PSA was affected. DESIGN: Serum was obtained from nine urological patients on 5 different days over a 2-week period. Free and total PSA levels were measured on the day of collection. The total variation expressed in terms of percent coefficient of variation (%CV) was calculated, and the biological variation was derived taking analytical variation into consideration. SETTING: Patients were from Seattle (Wash) Urological Associates, and samples were processed at the Dynacare Laboratory of Pathology, Seattle, Wash. PATIENTS: Nine men (aged 48 to 69 years) were evaluated; three had been diagnosed with prostate cancer, three with benign prostatic hyperplasia, one with chronic prostatitis, one with high-grade prostatic intraepithelial neoplasia, and one was clinically normal. MAIN OUTCOME MEASURES: Total variation for free, total, and percent free/total PSA. RESULTS: The average total variation was 13.9% CV, 7.5% CV, and 10.6% CV for free, total, and percent free/ total PSA, respectively. Biological variation was derived to be 13.0% CV, 5.6% CV, and 8.0% CV for free, total, and percent free/total PSA, respectively. CONCLUSIONS: When applied, these results suggest that there are significant random changes in the numerator and denominator of the free PSA-total PSA ratio that could result in clinical misinterpretation. Clinicians must be aware that free PSA and total PSA levels will fluctuate owing to nonpathologic variation.

Bladder surface glycosaminoglycans is a human epithelial permeability barrier.

Transitional epithelium of the bladder has been known to be impermeable. The data reported herein suggest the principal barrier to permeability may be glycosaminoglycans (GAG) of the surface of the bladder. We examined the ability of surface GAG to prevent a small molecule, urea, from moving across the epithelium in humans. It appears that GAG provide a physical barrier which prevents small molecules from reaching the underlying tight junctions and cell membranes and, hence, are a major permeability barrier. Normal volunteers (27) had 100 milliliters of a 200 grams per liter urea solution placed into their bladders for 45 minutes. Net flow of urea from the bladder lumen was 5.1 per cent. Volunteers who were capable of completing the study (19) had protamine sulfate (5 milligrams per milliliter) instilled in the bladder for 15 minutes, then removed and a second urea study done. Urea loss was significantly higher at 22 per cent (p less than 0.02). A solution of heparin (2,000 units per milliliter) was instilled for 15 minutes followed by a third urea study and urea loss was reversed to 9 per cent. All volunteers experienced significant urinary urgency and discomfort after protamine treatment which were reduced by heparin.

Epithelial dysfunction in nonbacterial cystitis (interstitial cystitis).

Traditional concepts of impermeability of the bladder have centered around unique cellular tight junctions and ion pumps. However, recent data from our laboratory have shown that the bladder epithelium in animals and humans relies primarily on its surface glycosaminoglycans to maintain its impermeability. This study demonstrates the first disease associated with an epithelial dysfunction of the bladder, that is a leaky epithelium. The study consisted of 31 normal subjects and 56 individuals with interstitial cystitis. Interstitial cystitis patients were shown to have a leaky epithelium by placing a solution of concentrated urea into the bladder and measuring the absorption. The normal subjects absorbed 4.3% in 45 minutes, while the interstitial cystitis patients absorbed 25% (difference is highly significant, p less than 0.005). Interstitial cystitis patients with Hunner's ulcers (10) had a 34.5% absorption rate, while those without ulcers absorbed 22.8% (46). This difference also was highly significant (p = 0.002) and supports the concept that patients with ulcers have clinically worse disease.

Rectourethral fistula caused by Kaposi's sarcoma.

A 35-year-old man with the acquired immunodeficiency syndrome-related complex was evaluated for a persistent urethral discharge, pneumaturia and watery diarrhea. Radiographic and endoscopic procedures established the diagnosis of a rectourethral fistula. Perineal exploration and excision of the fistula revealed the pathological diagnosis of Kaposi's sarcoma. The differential diagnosis of an acquired rectourethral fistula and the significance of Kaposi's sarcoma are discussed.