Haim Matzkin

A Novel Founder Mutation in the RNASEL Gene, 471delAAAG, Is Associated with Prostate Cancer in Ashkenazi Jews

HPC1/RNASEL was recently identified as a candidate gene for hereditary prostate cancer. We identified a novel founder frameshift mutation in RNASEL, 471delAAAG, in Ashkenazi Jews. The mutation frequency in the Ashkenazi population, estimated on the basis of the frequency in 150 healthy young women, was 4% (95% confidence interval [CI] 1.9%-8.4%). Among Ashkenazi Jews, the mutation frequency was higher in patients with prostate cancer (PRCA) than in elderly male control individuals (6.9% vs. 2.4%; odds ratio = 3.0; 95% CI 0.6-15.3; P=.17). 471delAAAG was not detected in the 134 non-Ashkenazi patients with PRCA and control individuals tested. The median age at PRCA diagnosis did not differ significantly between the Ashkenazi carriers and noncarriers included in our study. However, carriers received diagnoses at a significantly earlier age, compared with patients with PRCA who were registered in the Israeli National Cancer Registry (65 vs. 74.4 years, respectively; P<.001). When we examined two brothers with PRCA, we found a heterozygous 471delAAAG mutation in one and a homozygous mutation in the other. Loss of heterozygosity was demonstrated in the tumor of the heterozygous sib. Taken together, these data suggest that the 471delAAAG null mutation is associated with PRCA in Ashkenazi men. However, additional studies are required to determine whether this mutation confers increased risk for PRCA in this population.

Efficacy of sildenafil as adjuvant therapy to selective serotonin reuptake inhibitor in alleviating premature ejaculation

OBJECTIVES To evaluate the efficacy of sildenafil and selective serotonin reuptake inhibitor in alleviating premature ejaculation (PE) in patients in whom other treatments had failed. METHODS Healthy men evaluated for primary PE graded their ejaculation on a scale of 0 to 8 (0 = almost never, 8 = almost always). The intravaginal ejaculatory latency time (IVELT) was graded on a scale of 0 to 3 (0 = longer than 5 minutes, 3 = shorter than 1 minute). The 138 men who scored their PE as 4 or greater and IVELT as 2 or greater comprised the study group. Psychological and behavioral counseling was provided during the study. PE was graded using the same scales 3 months after the initiation of each treatment. Topical 5% lidocaine ointment comprised the initial treatment: dissatisfied patients (PE grade 4 or greater, IVELT 2 or greater), took one tablet of paroxetine 20 mg for 30 days and then one tablet 7 hours before intercourse. Sildenafil was added to the treatment of patients dissatisfied with paroxetine alone. RESULTS The mean initial PE grade was 5.67 +/- 0.13 and that for IVELT was 2.9 +/- 0.19 for all participants (mean age 28.7 years). Thirty-eight reported improvement (PE grade 2.0 +/- 0.8, P <0.01; IVELT 0.13 +/- 0.34, P <0.001) after local lidocaine application. Of the 100 treated with paroxetine, 42 reported improvement (PE grade 2.5 +/- 0.1, P <0.01; IVELT 0.28 +/- 0.46, P <0.001), and 56 of the remaining 58 who were treated with a combination of paroxetine and sildenafil reported improvement (PE grade 1.78 +/- 0.23, P <0.001; IVELT 0.16 +/- 0.37, P <0.001). Two patients remained dissatisfied with all treatment modalities. CONCLUSIONS Sildenafil combined with paroxetine and psychological and behavioral counseling alleviated PE in patients in whom other treatments failed.

Alfuzosin 10 mg once daily improves sexual function in men with lower urinary tract symptoms and concomitant sexual dysfunction

Associate Editor

Randomized prospective study of periprostatic local anesthesia during transrectal ultrasound-guided prostate biopsy.

OBJECTIVES To prospectively evaluate the efficacy of apical and lateral periprostatic lidocaine injection as anesthesia during transrectal ultrasound-guided prostate biopsy. METHODS A total of 152 consecutive men undergoing transrectal prostate biopsy in our department were enrolled in this study. Patients were randomized into group 1 (74 patients) who received 15 mL of 1% lidocaine in the lateral and apical periprostatic regions, 5 mL in each point, 10 minutes before the prostate biopsy, and group 2 (78 patients), controls. Pain after each biopsy (a total of 10 biopsies) was assessed using a 10-point linear visual analog pain scale. RESULTS In groups 1 and 2, the mean patient age was 64.8 and 65.8 years (P = 0.4), mean prostate-specific antigen was 10.9 and 11.2 ng/mL (P = 0.9), and mean prostate volume was 57 and 60 cm(3) (P = 0.5), respectively. The mean total pain score (sum of each biopsy score, total of 10 for each patient) during transrectal prostate biopsy was 16 (range 0 to 62.5) and 50 (range 0 to 100) in groups 1 and 2, respectively (P = 0.0001). No adverse events were noted. CONCLUSIONS Transrectal ultrasound-guided lateral and apical periprostatic anesthesia significantly diminishes the pain in men undergoing transrectal prostate biopsy. We recommend that this procedure be routinely offered to all patients undergoing transrectal prostate biopsy.

Does the rate of extracorporeal shock wave delivery affect stone fragmentation

OBJECTIVES To evaluate the effect of the rate of shock wave delivery on stone fragmentation, because the optimal rate of shock wave administration has not yet been established. METHODS Standard phantom, ball-shaped, ceramic stones were placed in a net-like basket with a hole size of 2.2 mm and immersed in a specially designed water bath coupled with the Econolith 2000 lithotripter. One hundred eighteen stones (mean diameter 9.5 mm) were used. Shock waves were delivered at rates of 30, 60, 90, 120, and 150 shocks/min and at intensities of 15, 20, and 22.5 kV (electrohydraulic). The number of shocks required for complete fragmentation, determined by all fragmented particles falling through the basket holes, was recorded. RESULTS The most effective (fewer shocks needed for complete stone fragmentation) rate of shock wave delivery was 60 shocks/min. A statistically significant difference was demonstrated between the mean number of shocks required for complete stone fragmentation at the rate of 60 shocks/min and faster rates at all energy levels (P <0.01) but not between the rate of 60 shocks/min and the rate of 30 shocks/min at all energy levels. CONCLUSIONS The rate of shock wave administration during extracorporeal shock wave lithotripsy seems to influence stone disintegration. We demonstrated that extracorporeal shock wave lithotripsy is most effective when waves are delivered at 60 shocks/min.

CLINICAL EFFICACY OF SILDENAFIL IN PATIENTS ON CHRONIC DIALYSIS

PURPOSE We evaluate the clinical efficacy of sildenafil citrate for patients who are on chronic dialysis and who have concomitant erectile dysfunction. MATERIALS AND METHODS A total of 35 men (mean age 60.7 years) on dialysis and with erectile dysfunction of various etiologies were administered 25 to 100 mg sildenafil for at least 6 months. The International Index of Erectile Function questionnaire (IIEF), a global assessment question and partner satisfaction question were used to evaluate sildenafil efficacy. Patients also reported any adverse events that occurred during treatment. RESULTS Treatment was effective for 28 of the 35 (80%) patients according to the results of the IIEF and global assessment questions. Partner satisfaction correlated with the IIEF overall response (0.79) and global assessment question results (0.86). No correlation was found between sildenafil failure and patient age, the etiology of erectile dysfunction, duration of erectile dysfunction, prior treatments, testosterone and prolactin blood levels, and the duration and etiology of renal failure. Of the 35 patients sildenafil was stopped due to intolerable headaches in 3 and because of lack of efficacy in 7. CONCLUSIONS Sildenafil is an effective and safe treatment for erectile dysfunction in most patients on chronic dialysis.

High detection rate of significant prostate tumours in anterior zones using transperineal ultrasound‐guided template saturation biopsy

Study Type – Diagnostic (exploratory cohort)

MSF-A Interacts with Hypoxia-Inducible Factor-1α and Augments Hypoxia-Inducible Factor Transcriptional Activation to Affect Tumorigenicity and Angiogenesis

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor in the signaling pathway that controls the hypoxic responses of cancer cells. Activation of the HIF system has been observed in carcinogenesis and numerous cancers. We found an interaction between a member of the mammalian septin gene family (MSF-A) and the HIF system. MSF-A is a nuclear protein that interacts with HIF-1alpha protein to prevent its ubiquitination and degradation, thus activating the HIF transcriptome. Cells overexpressing MSF-A protein exhibit increased HIF transcriptional activity and higher proliferation rates in vitro and in vivo. Xenograft-derived human tumors from these cells were larger and more vascular. These findings link a function of a septin protein with angiogenesis through activation of the HIF pathway.

Alfuzosin 10 mg once daily for treating benign prostatic hyperplasia: a 3-year experience in real-life practice

To assess the 3‐year efficacy and safety of the selective α1‐blocker alfuzosin at 10 mg once daily in men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) in ‘real‐life practice’. The influence of treatment response on the risk of acute urinary retention (AUR) and BPH‐related surgery was also analysed.

Sexual Dysfunction in Women Partners of Men With Erectile Dysfunction

We evaluated 113 female partners of men with erectile dysfunction (ED) attending a sexual dysfunction clinic in order to define sexual dysfunction among these women. In all, 51 (45%) women denied having any sexual dysfunction. The other 62 (55%) responded to questions classifying their complaint(s) according to the international classification of female sexual dysfunction (FSD) in the following topics (40/62, 65%, reported having more than one problem): decreased sexual desire (n=35, 56%), sexual aversion (none), arousal (n=23, 37%) and orgasmic disorders (n=39, 63%), dyspareunia (n=19, 31%), vaginismus (n=3, 5%), and noncoital sexual pain (none). Many female partners of men with ED report having some form of sexual disorder, mostly orgasmic problems and decreased sexual desire. Therefore, for optimal outcome of ED treatment, evaluation and treatment of male and FSD should be addressed as one unit within the context of the couple, and be incorporated into one clinic of sexual medicine.