Improvement of pressure flow parameters with finasteride is greater in men with large prostates. Finasteride Urodynamics Study Group

PURPOSE: We assess the effect of finasteride, a 5alpha-reductase inhibitor, on objective voiding parameters in men with lower urinary tract symptoms and benign prostatic enlargement on digital rectal examination (known as clinical benign prostatic enlargement) in a double-blind placebo controlled multicenter study using strict standard pressure flow study techniques. MATERIALS AND METHODS: A modification of the Abrams-Griffiths nomogram was used by 1 reader to ensure that all patients met objective criteria for bladder outlet obstruction at baseline. After performing a pressure flow study patients with obstruction were randomized 2:1 to receive 5 mg. finasteride (81) or placebo (40) daily. A second pressure flow study was performed at month 12. At baseline and month 12 free urinary flow studies and transrectal ultrasound were performed, and International Prostate Symptom Score questionnaires were completed. Patients were treated between May 1994 and July 1996. RESULTS: Finasteride caused a significant decrease (-8.1 cm. water) in detrusor pressure at maximum flow (p <0.05 versus placebo p = 0.02), increase (+1.1 ml. per second) in maximum flow rate (p <0.05 versus placebo p = 0.02) and decrease (-22.8%) in prostate volume (p <0.05 versus placebo p <0.001). Men with prostates larger than 40 cc had greater improvement in detrusor pressure at maximum flow (between group difference -14.5 cm. water, 95% confidence interval -26.2 to -2.6, p = 0.02) and maximum flow rate (mean treatment effect +1.6 ml. per second, 95% confidence interval -0.2 to 3.0, p = 0.02) compared to those with prostates 40 cc or less (between group differences not significant). CONCLUSIONS: Finasteride treatment resulted in improvements in urodynamic parameters, which were greater in men with large prostates.     

The natural history of lower urinary tract dysfunction in men: the influence of detrusor underactivity on the outcome after transurethral resection of the prostate with a minimum 10-year urodynamic follow-up

OBJECTIVES: To assess the long-term outcome of the efficacy of transurethral resection of the prostate (TURP) in men with detrusor underactivity (DUA), a cause of lower urinary tract symptoms (LUTS) in a significant minority of men. PATIENTS AND METHODS: Neurologically intact men with LUTS, who were investigated in our department between 1972 and 1986, diagnosed with DUA and who underwent surgical intervention, were invited for a repeat symptomatic and urodynamic assessment. Identical methods were used, allowing direct comparison of the results. RESULTS: In all, 224 men were initially diagnosed with DUA; 87 (39%) of these died in the interim and 22 followed had a TURP, with a mean follow-up since surgery of 11.3 years. There were no significantly sustained reductions in any symptoms. There was a small but significant reduction of questionable clinical significance in the bladder outlet obstruction index, but this did not translate into an improved flow rate. Comparison with 58 age-matched patients with DUA who remained untreated showed no significant advantage of surgical intervention in the long-term; on the contrary, there was more chronic retention in those who had had surgery. CONCLUSIONS: There are no long-term symptomatic or urodynamic gains from TURP in men shown to have DUA. The results of TURP in men with DUA are important, as urologists who surgically treat patients based on the symptoms and uroflowmetry alone will do so in a significant minority of men with DUA. These results strengthen the argument for a routine preoperative urodynamic assessment.     

Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the mir space station.

Bone loss is a current limitation for long-term space exploration. Bone markers, calcitropic hormones, and calcium kinetics of crew members on space missions of 4-6 months were evaluated. Spaceflight-induced bone loss was associated with increased bone resorption and decreased calcium absorption. INTRODUCTION: Bone loss is a significant concern for the health of astronauts on long-duration missions. Defining the time course and mechanism of these changes will aid in developing means to counteract these losses during space flight and will have relevance for other clinical situations that impair weight-bearing activity. MATERIALS AND METHODS: We report here results from two studies conducted during the Shuttle-Mir Science Program. Study 1 was an evaluation of bone and calcium biochemical markers of 13 subjects before and after long-duration (4-6 months) space missions. In study 2, stable calcium isotopes were used to evaluate calcium metabolism in six subjects before, during, and after flight. Relationships between measures of bone turnover, biochemical markers, and calcium kinetics were examined. RESULTS: Pre- and postflight study results confirmed that, after landing, bone resorption was increased, as indicated by increases in urinary calcium (p < 0.05) and collagen cross-links (N-telopeptide, pyridinoline, and deoxypyridinoline were all increased >55% above preflight levels, p < 0.001). Parathyroid hormone and vitamin D metabolites were unchanged at landing. Biochemical markers of bone formation were unchanged at landing, but 2-3 weeks later, both bone-specific alkaline phosphatase and osteocalcin were significantly (p < 0.01) increased above preflight levels. In studies conducted during flight, bone resorption markers were also significantly higher than before flight. The calcium kinetic data also validated that bone resorption was increased during flight compared with preflight values (668 +/- 130 versus 427 +/- 153 mg/day; p < 0.001) and clearly documented that true intestinal calcium absorption was significantly lower during flight compared with preflight values (233 +/- 87 versus 460 +/- 47 mg/day; p < 0.01). Weightlessness had a detrimental effect on the balance in bone turnover such that the daily difference in calcium retention during flight compared with preflight values approached 300 mg/day (-234 +/- 102 versus 63 +/- 75 mg/day; p < 0.01). CONCLUSIONS: These bone marker and calcium kinetic studies indicated that the bone loss that occurs during space flight is a consequence of increased bone resorption and decreased intestinal calcium absorption.     

Relationships between lower urinary tract symptoms and bladder outlet obstruction: Results from the ICS-“BPH” Study

Despite the lack of evidence in the literature for close relationships between lower urinary tract symptoms and bladder outlet obstruction, the majority of urologists rely on symptomatology when selecting patients for prostatic surgery. We investigated the relationships between a wide range of lower urinary tract symptoms from the ICSmale questionnaire and the results of urodynamic pressure and flow studies. We evaluated 933 patients with lower urinary tract symptoms suggestive for bladder outlet obstruction from 12 countries who participated in the ICS-“BPH” study with the ICSmale questionnaire and urodynamic pressure and flow studies. Spearman rank correlation coefficients were obtained between symptoms and measures of bladder outlet obstruction. There was little or no correlation between a wide range of symptoms and the results of free uroflowmetry and pressure and flow studies. From symptoms alone, it is not possible to diagnose bladder outlet obstruction. Pressure and flow studies and symptom profiles measure different aspects of the clinical condition that should be viewed separately in the evaluation and treatment decision of the patient presenting with lower urinary tract symptoms. Neurourol. Urodynam. 17:99–108, 1998. © 1998 Wiley-Liss, Inc.     

Expression of either NF-kappaB p50 or p52 in osteoclast precursors is required for IL-1-induced bone resorption.

Interleukin (IL)-1 is implicated in postmenopausal- and inflammation-mediated bone loss. Its expression is regulated by NF-kappaB and vice versa. To examine the role of NF-kappaB p50 and p52 (they are required for osteoclast formation during embryonic development) in IL-1-induced resorption, we used various NF-kappaB knockout (KO) mice, including p50-/- and p52-/- single KO, p50-/- and p52+/- (3/4KO), and p50-/- and p52-/- double KO (dKO) mice. IL-1 increased blood calcium and bone resorption in wild-type (wt), p50, and p52 single KO mice, but not in 3/4KO or dKO mice. Osteoclast formation was impaired in bone marrow cultures from 3/4KO compared with single KO and wt mice treated with IL-1. IL-1 receptor expression was similar in colony forming unit-granulocyte macrophage (CFU-GM) colony cells from wt and dKO mice. However, IL-1 promoted CFU-GM colony formation and survival as well as the formation, activity, and survival of osteoclasts generated from these colonies from wt mouse splenocytes, but not from dKO splenocytes. No difference in expression of the osteoclast regulatory cytokines, RANKL, and OPG, was observed in osteoblasts from wt and dKO mice. Thus, expression of either NF-kappaB p50 or p52 is required in osteoclasts and their precursors, rather than osteoblasts, for IL-1-mediated bone resorption.