Ejaculatory disorder by alpha-1 adrenoceptor antagonist in patients with benign prostatic hyperplasia; retrospective comparison between naftopidil and tamsulosin

We cross-sectionally studied the incidence and impact on quality of life of ejaculatory disorders caused by alpha-1 adrenoceptor antagonists (tamsulosin or naftopidil) in patients with benign prostatic hyperplasia (BPH). By questionnaire, we queried 88 clinical BPH patients concerning ejaculatory disorders, who were treated with tamsulosin or naftopidil between February 1999 and August 2003. We investigated the difference in the incidence and types of disorders between the two drugs. Of the 88 patients, 63 (71.6%) had sexual activities during the treatment. The incidence of ejaculatory disorders was significantly higher in the tamsulosin group (30.0%) than in the naftopidil group (3.0%). Eighty percent of patients having the disorders noticed the absence or reduced volume of semen although they experienced orgasms. The median quality of life index concerning the disorder was rated as 4, "mostly dissatisfied." Our results indicated that ejaculatory disorders occurred more frequently in the tamsulosin group. We should inform patients about this adverse effect caused by alpha-1 adrenoceptor antagonists prior to treatment.     

Relationship between prostate specific antigen and indexes of prostate volume in Japanese men

PURPOSE: We determined the relationship between serum prostate specific antigen (PSA) and indexes of prostate volume in Japanese men, and compared that relationship with the one in white men. MATERIALS AND METHODS: Data on a clinical cohort of 535 Japanese men with at least moderate lower urinary tract symptoms (LUTS) and clinical benign prostatic hyperplasia were examined. PSA, and total and transition zone prostate volume were related to age and linear regression analyses were performed to analyze the relationship between PSA and volume indexes. RESULTS: The group of 535 men with a median age of 68 years had a median serum PSA of 1.5 ng/ml, and a median total and transition zone volume of 26.8 and 8.8 ml, respectively. PSA, total prostate volume and transition zone volume increased almost linearly with age. On univariate regression with age with each successive decade total prostate volume increased by 10.65% (95% CI 5.4 to 16.2), transition zone volume increased by 20.84% (95% CI 11.84 to 30.56) and the transition zone index increased by 3.1% (95% CI 1.66 to 4.57). On multivariate analysis the PSA-total prostate volume relationship was statistically independent of age. The study suggests that Japanese men might produce or release more PSA per unit prostate volume than white men. CONCLUSIONS: Japanese men with LUTS and clinical benign prostatic hyperplasia but no evidence of prostate cancer might produce and/or release more PSA per unit prostate volume than white men. To our knowledge the cutoffs for PSA and prostate volume to predict the response to LUTS therapy and the development of complications in Japanese men are unknown. Future studies in Japanese men are needed to identify these cutoffs.     

Web-based research of lower urinary tract symptoms that affect quality of life in elderly Japanese men: analysis using a structural equation model

OBJECTIVE: To investigate the distribution of lower urinary tract symptoms (LUTS) in elderly Japanese men, to clarify which variables contributed to medical care-seeking behaviour, and to construct a structural-equation model (SEM) to explain overall quality of life (QoL). SUBJECTS AND METHODS: A dataset was obtained from 662 Japanese men aged 50-79 years who participated in the programme by accessing a website via the Internet between 10.30 hours on 19 February 2003 and 10.30 hours on 24 February 2003. The participants were queried about their International Prostate Symptom Score (IPSS), bother, QoL index and medical care-seeking behaviour. RESULTS: Of the 662 participants, 314 reported intending to seek medical care for LUTS (intention group); the remaining 348 answered that they did not intend to see a doctor (no-intention group). The characteristic of weak stream had the strongest correlation with the QoL index, not only in the intention (r = 0.58) but also in the no-intention group (r = 0.48). Among several SEMs proposed, one that included a latent variable termed 'QoL sensitivity' was the most appropriate to explain overall QoL. In this model it was assumed that 'QoL sensitivity' was affected by other latent variables, termed the 'voiding symptom factors' and 'storage symptom factors', and affected the degree of bother related to each symptom. CONCLUSION: In Japanese men, voiding symptoms, especially weak stream, contributed to overall QoL for medical care-seeking behaviour. Differences in 'QoL sensitivity' among men may be one of the reasons why symptomatic severity is not always correlated with symptom-related bother.     

Characterization of prostatic neuroendocrine cell line established from neuroendocrine carcinoma of transgenic mouse allograft model

BACKGROUND: The role of neuroendocrine (NE) cells in prostate cancer remains unclear. A useful model is necessary to study the biology of NE cells. We herein describe the establishment and characterization of an immortalized cell line from an NE-10 allograft of murine prostatic NE carcinoma. METHODS: A novel cell line, designated NE-CS, was developed from an NE-10 allograft that was established from the ventral prostate of the LPB-T-antigen (Tag) transgenic mouse, line 10 (12T-10). We investigated the growth, karyotype, electron microscopic findings, expression of Tag and androgen receptor (AR), and tumorigenesis of the cells in athymic mice. RESULTS: The immortal cell line NE-CS was maintained in vitro for more than 2 years. The NE-CS cells had dendritic-like extensions with dense core granules in the cytoplasm and produced serotonin and somatostatin in conditioned medium. The cells expressed neither Tag nor AR. They showed androgen-independent growth in vitro and a hypotetraploid karyotype similar to the original NE-10 allograft. The NE-CS cells, which were subcutaneously inoculated into athymic mice, formed tumors with the NE phenotype. The tumors exhibited accelerated growth compared to the original NE-10 allograft. CONCLUSIONS: The established cell line has characteristics of NE differentiation and tumorigenic ability. This cell line may be a promising model to understand the molecular mechanisms associated with the acquisition of hormone refractory prostate cancer.     

Membrane-Anchored CD14 Is Important for Induction of Interleukin-8 by Lipopolysaccharide and Peptidoglycan in Uroepithelial Cells

We investigated the induction of interleukin-8 (IL-8) by bacterial lipopolysaccharide (LPS) and peptidoglycan (PGN) in the bladder cancer cell lines T24, 5637, UM-UC-3, and HT1197. T24 and 5637 cells strongly induced IL-8 after stimulation with LPS or PGN in a dose- and time-dependent manner, whereas UM-UC-3 and HT1197 cells did so very weakly. The expression of CD14 at the mRNA, total cellular protein, and cell surface protein levels differed among these cell lines, but the expression levels of Toll-like receptors 2 and 4 (TLR2 and TLR4) were not significantly different. The CD14 expression levels were found to correlate with the inducibility of IL-8 by LPS or PGN. Treatment of T24 and 5637 cells with phosphatidylinositol-specific phospholipase C to eliminate CD14 from the cell surface dramatically suppressed the induction of IL-8. On the other hand, UM-UC-3 cells transfected with CD14 cDNA expressed membrane-anchored CD14 and showed more efficent induction of IL-8 by LPS stimulation than untransfected controls. These results suggest that the presence of the membrane-anchored, but not the soluble, form of CD14 is a strong factor in IL-8 induction in bladder epithelial cells in response to bacterial components. The presence of the membrane-anchored form of CD14 may thus be a determinant for the inflammatory response of uroepithelial cells.     

Reference control data obtained from an in vivo comet-micronucleus combination assay using Sprague Dawley rats

According to the International Conference on Harmonization Guidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use (ICH S2(R1)), a positive response in any in vitro assay necessitates additional in vivo test(s) (other tissue/endpoint) in addition to the erythrocyte micronucleus test when Option 1 of the test battery is selected. When Option 2 of the test battery is selected, a bacterial gene mutation test and two in vivo tests with different tissues/endpoint are required. The in vivo alkaline comet assay is recommended as the second in vivo test because it can detect a broad spectrum of DNA damage in any tissue and can be combined with the erythrocyte micronucleus test. Considering animal welfare, a combination assay is preferable to an individual assay. Thus, we validated the protocol for the in vivo comet-micronucleus combination assay in rats with three daily administrations and determined the dose of the positive control (ethyl methanesulfonate; EMS, 200 mg/kg/day). We also collected the negative control (vehicle) and positive control (EMS) data from the comet (liver, stomach, and kidney) and micronucleus (bone marrow) combination assay using male Sprague Dawley (SD) rats. The negative control data were comparable to our historical control data obtained from stand-alone assays. The positive control data showed clear and consistent positive responses in both endpoints.     

Risk factors for multiple intravesical recurrences of superficial bladder cancer

Objectives. To elucidate the risk factors for a second or third intravesical recurrence in patients with superficial bladder cancer.Methods. Of 84 consecutive patients newly diagnosed as having superficial bladder cancer in Sapporo Medical University Hospital, 30 patients who had at least one recurrent superficial bladder cancer and were followed up for more than 3 years were included in this study. Multivariate analysis by Cox’s proportional hazards model was used to determine which clinical and pathologic variables significantly affected the second and third recurrences. Stepwise regression analysis was used to determine which clinical and pathologic variables significantly affected multiple recurrences of bladder cancer.Results. The 1, 2, and 5-year recurrence-free rates as determined by the Kaplan-Meier method were 66.1%, 43.8%, and 29.8% for a second recurrence and 67.4%, 61.8%, and 39.2% for a third recurrence, respectively. Multivariate analysis revealed that only the interval between the initial transurethral resection of the bladder cancer and the first recurrence was a significant and independent factor affecting the second recurrence. In the study of the third recurrence, the interval between the first and second recurrences was the only definite risk factor for the third one. When multiple recurrences were considered, stepwise regression analysis revealed that a time of 6 months or less from the initial transurethral resection until the first recurrence was a significant factor that affected the total frequency of bladder cancer recurrence (R² = 0.220, P = 0.0078).Conclusions. The results of our study indicate that patients will have the potential for frequent recurrences if they have the disease with recurrence after a short interval. This result may contribute to the selection of patients with superficial bladder cancer to receive aggressive adjuvant treatments to prevent frequent recurrences.