PSA quo vadis? It is reasonable to start with prostate-specific antigen testing at the age of 40!

BACKGROUND: It is common to start with PSA (prostate-specific antigen)-testing at the age of 50. If patients with a PSA value greater than 4 ng/mL should be considered for prostate biopsy, approximately 20% of all men undergoing test are considered for biopsy at the time of first early-detection examination. METHODS: We have screened 2,592 asymptomatic men younger than 45 years. With a short questionnaire, we assessed age, body mass index (BMI), concomitant diseases, last sexual intercourse, and last bicycle riding. We compared this cohort with a group of 11,656 men aged 45-75 years from a nationwide prostate cancer screening trial. RESULTS: In this cohort, only 4 men with a PSA value greater than 4 ng/mL and 10 with a PSA greater than 3 ng/mL were identified. More than 99% of all men younger than 45 years had a PSA lesser than 4 ng/mL. Sexual intercourse, bicycle riding, or BMI had a significant but minimal influence on the PSA value. CONCLUSIONS: It is reasonable to start with PSA testing at the age of 40 years. The advantage of screening younger patients is that almost no one should be considered for biopsy at the time of first early-detection examination. We identified a baseline value at which only a minimal influence was exerted by benign prostatic hypertrophy. In comparison with many current guidelines, we gained a lead time of 10 years for observation of PSA dynamics. IMPACT: The importance of PSA velocity for stratification of patients at risk for development of significant prostate cancer will grow.

The treatment of stress incontinence in men: part 2 of a series of articles on incontinence.

BACKGROUND: Stress incontinence in men is a rare, usually iatrogenic condition. Its prevalence can be expected to rise in the future because of the increasingly common performance of radical prostatectomy. Most men who have undergone prostatectomy experience a transient disturbance of urinary continence. Such disturbances are only rarely due to structural damage to the sphincter apparatus and therefore have a good prognosis for spontaneous recovery. METHOD: Selective literature review. RESULTS: Pelvic floor training and/or pharmacotherapy can be used for more rapid restoration of subjectively satisfactory urinary continence. If the sphincter is intact, continence can also be regained in the early postoperative period through the submucosal injection of bulking agents. Incontinent patients whose urinary sphincter is dysfunctional because of denervation or direct injury to striated muscle can now be treated with a variety of surgical techniques. The implantation of an artificial sphincter is the gold standard of therapy. Properly selected and informed patients can also be treated with minimally invasive procedures, such as the creation of a male suburethral sling, although the experience with such procedures to date has not been extensive. CONCLUSION: Post-prostatectomy incontinence has a good prognosis and should thus be treated conservatively at first. If it nonetheless persists, surgical treatment is indicated for patients who choose it after being fully informed about their options.

8-pCPT-conjugated cyclic AMP analogs exert thromboxane receptor antagonistic properties.

Membrane-permeable 8-(4-chlorophenylthio)-2'-O-methyl cyclic AMP (8-pCPT-2'-O-Me-cAMP) has been shown to specifically activate cAMP-regulated Epac proteins, without direct effects on protein kinase A and protein kinase G. During isometric tension measurements in thoracic aortic rings from Wistar rats, we observed that 8-pCPT-2'-O-Me-cAMP selectively induced a rightward shift of the concentration response curve for the thromboxane mimetic U46619, without altering the contractile response to noradrenaline. We hypothesised that 8-pCPT-2'-O-Me-cAMP and similar compounds may function as direct thromboxane receptor antagonists. Indeed, in addition to 8-pCPT-2'-O- Me-cAMP, also 8-pCPT-cAMP, 8-(4-chlorophenylthio)-adenosine-3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-8-CPT-cAMPS) and 8-CPT-adenosine, but not 8-Bromo-2'-O-Me-cAMP, induced rightward shifts of the contractile response to U46619. Likewise, 8-pCPT-2'-O- Me-cAMP and Rp-8-CPT-cAMPS, but not 8-Bromo-2'-O-Me-cAMP, specifically reduced U46619-induced aggregation of human platelets. In addition, 8-pCPT-2'-O-Me-cAMP and Rp-8-CPT-cAMPS completely reversed U46619-induced reduction of intercellular adhesion molecule-1 expression and migration of human coronary artery endothelial cells. Most important, the cAMP analogs that reduced the contractile response to U46619 also concentration-dependently inhibited binding of the thromboxane receptor radioligand [5,6-3H]SQ29548 to human platelets. We conclude that 8-pCPT-conjugated cAMP analogs exert competitive thromboxane receptor antagonistic properties.

The Zeiss-loop stone extraction: minimal invasive and effective or obsolete?

PURPOSE: Through the introduction of ureterorenoscopy (URS) and extracorporal shock wave lithotripsy (ESWL) into stone treatment, the Zeiss-loop procedure has lost more and more its importance. Current guidelines recommend on the level of an expert-opinion, that stone extraction without endoscopic-visual control should not be performed anymore. Nevertheless, stone extraction using the Zeiss-loop is still being performed in our clinic and therefore we wanted to determine its position in stone treatment in the age of URS and ESWL. METHODS: The data of 253 patients with ureter stones, who were treated with the Zeiss-loop were evaluated. The loop is always pulled through completely under radiological control. RESULTS: In 221 cases, the concrement was located in the distal ureter. All concrements have been maximally 10 mm in size. Independently of size and position, in 219 patients the loop extraction resulted in a complete stone removal. Complication rates are low. No complete tear-off of the ureter occurred. The overall success rates of loop extraction were superior to those of ESWL in ureter stones but worse than URS. Referring to distal stones, success rates are similar, but stones treated by URS have been bigger. CONCLUSIONS: Therefore, in our opinion, immediate stone extraction under fluoroscopic control with the Zeiss-loop, is still a possible treatment alternative for small distal stones (<10 mm). Being aware of these first "new" data of an old procedure, the Zeiss-loop will still play a role in endoscopic stone treatment in our department and should not be completely abandoned due to its bad reputation.

Cyclic AMP-dependent and Epac-mediated activation of R-Ras by G protein-coupled receptors leads to phospholipase D stimulation.

The activation of the Ras-related GTPase R-Ras, which has been implicated in the regulation of various cellular functions, by G protein-coupled receptors (GPCRs) was studied in HEK-293 cells stably expressing the M3 muscarinic acetylcholine receptor (mAChR), which can couple to several types of heterotrimeric G proteins. Activation of the receptor induced a very rapid and transient activation of R-Ras. Studies with inhibitors and activators of various signaling pathways indicated that R-Ras activation by the M3 mAChR is dependent on cyclic AMP formation but is independent of protein kinase A. Similar to the rather promiscuous M3 mAChR, two typical G(s)-coupled receptors also induced R-Ras activation. The receptor actions were mimicked by an Epac-specific cyclic AMP analog and suppressed by depletion of endogenous Epac1 by small interfering RNAs, as well as expression of a cyclic AMP binding-deficient Epac1 mutant, but not by expression of dominant negative Rap GTPases. In vitro studies demonstrated that Epac1 directly interacts with R-Ras and catalyzes GDP/GTP exchange at this GTPase. Finally, it is shown that the cyclic AMP- and Epac-activated R-Ras plays a major role in the M3 mAChR-mediated stimulation of phospholipase D but not phospholipase C. Collectively, our data indicate that GPCRs rapidly activate R-Ras, that R-Ras activation by the GPCRs is apparently directly induced by cyclic AMP-regulated Epac proteins, and that activated R-Ras specifically controls GPCR-mediated phospholipase D stimulation.