The induction and maintenance of in vitro plant morphogenesis as viewed from a new perspective, with theoretical and constructive implications.

In plant tissue culture research, the non-traditional growth regulators, methylglyoxal and ascorbic acid, have been used to induce and promote in vitro morphogenesis from plant callus, generally having the initial characteristics of a type of neoplasm, and in many cases overcoming recalcitrant morphogenesis. In other investigations methylglyoxal, most likely with ascorbic acid, also promoted such morphogenesis. In the various investigations, low concentrations of methylglyoxal were used and proved to be the most effective in promoting in vitro morphogenesis. In many cases, the growth of such neoplastic-like calli was concurrently inhibited on culture media containing these chemicals. When methylglyoxal was present in high concentration, morphogenesis was also inhibited. Such chemicals, it would appear likely, allowed for the generation of cohesive forces within regions of the calli, reversing the neoplastic state in such regions, due to very low internal cohesion, and through such cohesive forces of particular magnitude, morphogenesis ensued, as an adaptive response to the stress of such cohesive forces. This would suggest a deeper, underlying biological process, with developmental features, that is perhaps universal among plants and perhaps in all biological organisms. This particular, consistent avenue and theme of plant tissue culture research, manifested over four decades and across four continents, may have revealed a unifying, dynamical process in both the biological and physical worlds, with constructive implications for agriculture and medicine.

Factors associated with adherence to an end-of-study biopsy: lessons from the prostate cancer prevention trial (SWOG-Coordinated Intergroup Study S9217).

BACKGROUND: The Prostate Cancer Prevention Trial (PCPT) was a 7-year randomized, double-blind, placebo-controlled trial of the efficacy of finasteride for the prevention of prostate cancer with a primary outcome of histologically determined prevalence of prostate cancer at the end of 7 years. METHODS: A systematic modeling process using logistic regression identified factors available at year 6 that are associated with end-of-study (EOS) biopsy adherence at year 7, stratified by whether participants were ever prompted for a prostate biopsy by year 6. Final models were evaluated for discrimination. At year 6, 13,590 men were available for analysis. RESULTS: Participants were more likely to have the EOS biopsy if they were adherent to study visit schedules and procedures and/or were in good health (P < 0.01). Participants at larger sites and/or sites that received retention and adherence grants were also more likely to have the EOS biopsy (P < 0.05). CONCLUSIONS: Our results show good adherence to study requirements 1 year before the EOS biopsy was associated with greater odds that a participant would comply with the invasive EOS requirement. IMPACT: Monitoring adherence behaviors may identify participants at risk of nonadherence to more demanding study end points. Such information could help frame adherence intervention strategies in future trials.

Racial differences in longitudinal changes in serum prostate-specific antigen levels: the Olmsted County Study and the Flint Men's Health Study.

OBJECTIVE: To determine the distribution of, and racial differences in, changes in prostate-specific antigen (PSA) from a population-based sample of men. MATERIALS AND METHODS: Data from 2 prospective cohort studies of a random sample of white men, aged 40-79 years in 1990, followed biennially through 2007, and African American men, aged 40-79 years in 1996, followed through 2000, were examined to assess the longitudinal changes in PSA concentrations. Serum PSA levels were determined at each examination for both cohorts and observations after a diagnosis of prostate cancer or treatment of benign prostatic hyperplasia were censored. The observed and estimated annual percentage of change in the serum PSA levels were examined by race. RESULTS: At baseline, the median PSA level in the white men did not differ from the median level observed in the African American men (white men 0.9 ng/mL; African American men 0.9 ng/mL; P = .48). However, African American men had a much more rapid increase in the PSA level over time compared with the white men (median annual percent change in PSA for white men 3.6%/y, African American men 7.9%/y; P <.001). CONCLUSION: These data suggest that African American men have more rapid rates of change in the PSA levels over time. If the difference in the rate of changes between African American and white men is an early indicator of future prostate cancer diagnosis, earlier detection in African American men could help to alleviate the racial disparities in prostate cancer diagnosis and mortality.

New practical and theoretical approaches to the induction of morphogenesis from plant tumors in vitro using new types of plant growth regulators: towards constructive paradigms in agriculture and medicine.

Using classical or traditional plant growth regulators, calli or plant tumors have been produced in vitro and subsequently have been induced to produce buds and plantlets, a process referred to as regeneration. For many years, this has been a successful procedure for in vitro, plant propagation. However, for a number of plant species investigators could not induce calli in vitro to produce buds. Organogenesis was still recalcitrant for various plants in 1980. New types or nonconventional growth regulators, such as methylglyoxal and ascorbic acid, were then found to overcome recalcitrant organogenesis in vitro. Their successful or effective use gave support to a theory that stressful, non-uniform cohesive force-fields, electromagnetic in nature, occurring through the application of certain chemicals, are necessary for in vitro morphogenesis from plant neoplasm or callus. Morphogenesis is seen as an adaptive accommodation to the inner stresses from such non-uniform, cohesive forces. Diverse chemicals, not considered traditional plant growth regulators would, it has been conjectured, enable the generation of such cohesive forces, in non-uniform arrays, and it has been predicted that more chemicals of this type will be discovered. A new constructive approach to agriculture and medicine, using a new plant tissue-culture model, based on new theory, has also been predicted.

Effectiveness of medical and surgical therapies for lower urinary tract symptoms in the community setting.

UNLABELLED: Study Type - Therapy (outcomes research) Level of Evidence 2c. What's known on the subject? and What does the study add? It is known that benign prostatic hyperplasia is a common condition affecting most men by the age of 80 years. There are multiple treatment options available, including both medical and surgical interventions. However, what is not known is how affective the different types of interventions are in the general population. Previous studies have focused on centre-specific data. What is unique about our study is that it is a prospective cross-section analysis of a community cohort of men. Through this study we were able to assess the outcomes in the general population as opposed to in a high-volume surgical centre. Our findings show that in this community medical management was poor at symptomatic improvement, whereas surgical intervention produced the best improvement. OBJECTIVE: • To describe the use and symptomatic outcomes of different therapies for lower urinary tract symptoms (LUTS) in a community-based population of men followed for 17 years. PATIENTS AND METHODS: • Data from a randomly selected cohort of 2184 men, aged 40-79 years in 1990, from Olmsted County, Minnesota, USA were included in the study. Participants completed a questionnaire similar to the American Urological Association Symptom Index (AUASI) and reported on incontinence. • Men were followed biennially through 2007 (median follow-up: 13.7 years; Q1, Q3: 8.8, 15.7). Medical and surgical treatments for LUTS were reported on biennial questionnaires and abstracted from community medical records. RESULTS: • Overall, 610 (28%) men received medical or surgical therapy for treatment of LUTS. Patients undergoing vaporization and transurethral resection of the prostate (TURP) had the highest pre-intervention AUASI scores (P < 0.001) and the most rapid increase in scores over time (P= 0.002) compared with those treated with medications or no therapy. After intervention, symptom progression slowed in all treatment groups. • However, the greatest improvement in AUASI score (median % change) was observed in the TURP group: -27.45%. The TURP group also reported a significant decrease in incontinence after surgery (% change): TURP: -22.58%. CONCLUSION: • All therapies were effective at slowing the progression of LUTS, but only TURP patients reported a significant decrease in both LUTS and incontinence after therapy.

Longitudinal changes of benign prostate-specific antigen and [-2]proprostate-specific antigen in seven years in a community-based sample of men.

OBJECTIVE: To determine the longitudinal changes of benign prostate-specific antigen (BPSA) and [-2]proPSA and how these changes relate to the outcomes. These markers have been shown to be predictive of prostate cancer (CaP) and benign prostatic hyperplasia treatment; however, little is known about longitudinal changes in these markers. METHODS: In 1990, a 25% subsample from a cohort of white men aged 40-79 years, who were randomly selected from Olmsted County, Minnesota residents, completed a detailed clinical examination. BPSA and [-2]proPSA were measured from frozen sera. The men were evaluated biennially (median follow-up 7 years; range 0-8.8). Mixed-effects regression models were used to estimate the longitudinal changes in the BPSA and [-2]proPSA levels overall and by outcomes. Spearman correlations were used to compare these changes with the baseline levels and the annualized changes in urologic measures. RESULTS: The median and 25th and 75th percentiles annualized percent change for [-2]proPSA and BPSA was 3.7%, 2.5% and 5.2% and 7.3%, 6.8%, and 7.7%, respectively. The annualized percent change for both markers correlated with the baseline and annualized changes in PSA and prostate volume. The annualized percent change increased with increasing age decade for [-2]proPSA but not for BPSA. The rate of increase in [-2]proPSA was significantly greater for men who developed enlarged prostates (median 3.5%, 25th and 75th percentile 2.6% and 4.4%, respectively) or CaP (median 8.1%, 25th and 75th percentile 6.6% and 9.8%, respectively) compared with those who did not develop enlarged prostates (median 1.9%, 25th and 75th percentile 0.9% and 3.0%, respectively) or CaP (median 3.5%, 25th and 75th percentile 2.3% and 4.8%, respectively). CONCLUSION: BPSA and [-2]proPSA levels increase over time. The annualized percent change in [-2]proPSA increases with age and might be a useful predictor of CaP development.

Nocturia is associated with an increased risk of coronary heart disease and death.

UNLABELLED: What's known on the subject? and What does the study add? Nocturia has been associated with multiple chronic conditions, however, previous studies have been conducted only at a single time. We found that nocturia preceded the development CHD in young men. Moderate nocturia may be an early marker of CHD in young men. OBJECTIVE: To determine whether nocturia is associated with the development of diabetes mellitus, hypertension, coronary heart disease (CHD) and occurrence of death. MATERIALS AND METHODS: We studied data obtained from a retrospective cohort of randomly selected men, aged 40-79 years in 1990, from Olmsted County, MN, USA. Moderate nocturia was defined as waking to urinate ≥2 times per night. Men were followed every 2 years through repeated questionnaires and community medical records to assess development of diabetes mellitus and hypertension, and occurrence of death. CHD was ascertained through ongoing surveillance of heart disease in Olmsted County. Cox proportional hazard models were used to estimate associations between baseline nocturia and each of the outcomes. RESULTS: A total of 2447 men were followed for a median of 17.1 years (25th and 75th percentiles: 15.0, 17.4 years). Moderate nocturia was not significantly associated with the later development of diabetes mellitus or hypertension in this study. Younger men (<60 years of age) with moderate nocturia were more likely to develop CHD later in life than younger men without nocturia (hazard ratio [HR]: 1.68; 95% confidence interval [CI]: 1.13, 2.49). This association was no longer significant when adjusted for age, body mass index (BMI) and urological medications (HR: 1.36; 95% CI: 0.87, 2.12). Older men (≥60 years of age) with moderate nocturia were more likely to die than older men without moderate nocturia, even after adjusting for age, BMI, urological medications and CHD (HR: 1.48; 95% CI: 1.15, 1.91). CONCLUSION: Nocturia may be a marker for increased risk of CHD in younger men, and death in older men.

Sixteen-year longitudinal changes in serum prostate-specific antigen levels: the olmsted county study.

OBJECTIVE: To determine the distribution of longitudinal changes in serum prostate-specific antigen (PSA) levels from a population-based sample of men. PATIENTS AND METHODS: In this prospective cohort study, a random sample of Olmsted County, Minnesota, men aged 40 to 79 years in 1990 were followed up biennially from January 1, 1990, through August 29, 2007. Serum PSA levels were determined at each examination, and men were censored for follow-up with a diagnosis of prostate cancer or treatment for benign prostatic hyperplasia. The empirical distributions of annual percent change and annual absolute change in serum PSA level were calculated and tabulated, including the median and 75th and 95th percentiles. RESULTS: For men with PSA measurements 2 years apart, the median annual percent change in serum PSA level was 4.83% and the 95th percentile was about 49.76%. The variability in estimated annual change decreased with increasing time between assessments, with a 95th percentile of 21.82% after 8 or more years between assessments. Although the median absolute change per year increased with increasing age, the median percent change per year was fairly consistent across age groups. CONCLUSION: These data demonstrate that, with shorter intervals between assessments, greater variability should be expected. These distributions should prove helpful to patients and clinicians in interpreting changes in serum PSA levels observed in typical clinical practices.

Distribution and associations of [-2]proenzyme-prostate specific antigen in community dwelling black and white men.

PURPOSE: We provide cross-sectional normative data on [-2]proenzyme-prostate specific antigen from the Olmsted County Study of Urinary Symptoms and Health Status among Men, and the Flint Men's Health Study. We also describe associations with clinical urological measures and the risk of prostate cancer diagnosis. MATERIALS AND METHODS: Measurements of [-2]proenzyme-prostate specific antigen were obtained from 420 white men from Olmsted County, Minnesota, and 328 black men from Genesee County, Michigan. Cross-sectional associations between [-2]proenzyme-prostate specific antigen and prostate enlargement/elevated prostate specific antigen were assessed. Cox proportional hazard models were used to assess associations between [-2]proenzyme-prostate specific antigen and the incident diagnosis of prostate cancer. RESULTS: Baseline [-2]proenzyme-prostate specific antigen was slightly higher in black men at a median of 6.3 pg/ml (25th, 75th percentiles 4.1, 8.9) than in white men at a median of 5.6 pg/ml (25th, 75th percentiles 3.9, 7.7, respectively, p = 0.01). Baseline [-2]proenzyme-prostate specific antigen was highly predictive of biopsy confirmed prostate cancer in the Olmsted County Study cohort. Relative to men in the [-2]proenzyme-prostate specific antigen lower quartile those in the upper quartile were at almost eightfold increased risk for prostate cancer (HR 7.8, 95% CI 2.2-27.8) after adjusting for age and baseline prostate specific antigen. CONCLUSIONS: In these cohorts of community dwelling black and white men [-2]proenzyme-prostate specific antigen was much lower than in previous studies. These data suggest that [-2]proenzyme-prostate specific antigen may help identify prostate cancer in men with serum prostate specific antigen in an indeterminate range, although the reference ranges for white and black men may differ slightly.

Benign prostate specific antigen distribution and associations with urological outcomes in community dwelling black and white men.

PURPOSE: We describe cross-sectional associations of benign prostate specific antigen with clinical urological measures and examined the risk of future urological outcomes in 2 population based cohorts of black and white men, respectively. MATERIALS AND METHODS: Two population based cohort studies were established to characterize the natural history of and risk factors for prostate disease progression in white and black male residents of Olmsted County, Minnesota, and Genesee County, Michigan, respectively. RESULTS: The benign prostate specific antigen distribution was similar in black men at a median of 32.9 pg/ml (25th, 75th percentiles 17.3, 68.0) and white men at a median of 32.2 pg/ml (25th, 75th percentiles 16.6, 68.9, respectively). However, it was much lower than in previous reports. For Olmsted County men in the upper quartile of benign prostate specific antigen there was a fifteenfold increased risk of prostate cancer (HR 14.6, 95% CI 3.1-68.6) and a twofold higher risk of treatment for benign prostatic hyperplasia (HR 2.2, 95% CI 1.2-4.2) after adjusting for age. After additional adjustment for baseline prostate specific antigen the association between benign prostate specific antigen and prostate cancer risk was attenuated but remained almost ninefold higher for men in the upper quartile of benign prostate specific antigen (HR 8.7, 95% CI 1.8-42.4). The twofold higher risk of treatment for benign prostatic hyperplasia also remained after adjusting for baseline prostate specific antigen for men in the upper benign prostate specific antigen quartile (HR 1.9, 95% CI 0.9-4.0). CONCLUSIONS: Results suggest that increased benign prostate specific antigen may help identify men with prostate cancer and those at risk for benign prostatic hyperplasia treatment.

Diabetes treatment and progression of benign prostatic hyperplasia in community-dwelling black and white men.

OBJECTIVE: To conduct a study to determine whether diabetes treatment is associated with benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) and progression in black and white men. Diabetes has been associated with BPH and LUTS in aging men. METHODS: Using the Olmsted County Study of Urinary Symptoms and Health Status among Men and the Flint Men's Health Study, we examined how the use of medical therapy (eg, insulin regimens, oral hypoglycemics) related to changes in LUTS severity, maximal urinary flow rate measured by uroflowmetry, prostate volume determined by transrectal ultrasonography, and serum prostate-specific antigen concentrations. RESULTS: Of the 2226 men participating in the Olmsted County Study of Urinary Symptoms and Health Status among Men and the Flint Men's Health Study, 186 men reported a history of diabetes, 76.9% of whom were treated with medical therapy. Overall, the men with diabetes had significantly greater odds of moderate/severe LUTS (age- and race-adjusted odds ratio 1.37, 95% confidence interval 1.00-1.87) compared with those without diabetes. However, among the diabetic men, those not taking medication had greater odds of moderate/severe LUTS than those taking medication. This association among men not taking medication was seen for 5 of the 7 individual symptoms. The prostate volume and prostate-specific antigen level were not significantly associated with diabetes treatment. No significant differences were observed for the annual change in BPH characteristics by diabetes treatment status. CONCLUSION: These findings suggest that the presence of diabetes and subsequent poor glycemic control might be less related to prostate growth and more to the dynamic components of lower urinary tract function. Additional evaluations of the associations between glycemic control and BPH progression are warranted.

Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

CONTEXT: The initial report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a statistically nonsignificant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer. OBJECTIVE: To determine the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men. DESIGN, SETTING, AND PARTICIPANTS: A total of 35,533 men from 427 study sites in the United States, Canada, and Puerto Rico were randomized between August 22, 2001, and June 24, 2004. Eligibility criteria included a prostate-specific antigen (PSA) of 4.0 ng/mL or less, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for all others. The primary analysis included 34,887 men who were randomly assigned to 1 of 4 treatment groups: 8752 to receive selenium; 8737, vitamin E; 8702, both agents, and 8696, placebo. Analysis reflect the final data collected by the study sites on their participants through July 5, 2011. INTERVENTIONS: Oral selenium (200 µg/d from L-selenomethionine) with matched vitamin E placebo, vitamin E (400 IU/d of all rac-α-tocopheryl acetate) with matched selenium placebo, both agents, or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years. MAIN OUTCOME MEASURES: Prostate cancer incidence. RESULTS: This report includes 54,464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report. Compared with the placebo (referent group) in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (hazard ratio [HR], 1.17; 99% CI, 1.004-1.36, P = .008); as did 575 in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; P = .18), and 555 in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22, P = .46). Compared with placebo, the absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination. CONCLUSION: Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00006392.

Associations between modest weight changes and onset and progression of lower urinary tract symptoms in two population-based cohorts.

OBJECTIVES: To conduct a study to determine whether weight changes were associated with the risk of developing lower urinary tract symptoms (LUTS). Obesity has been associated with LUTS in aging men. METHODS: The study population consisted of men participating in the Olmsted County Study of Urinary Symptoms and Health Status among Men and the Flint Men's Health Study. Weight loss and weight gain were defined as a change of ≥5% of the baseline weight. LUTS progression was measured by calculating the American Urological Association Symptom Index (AUASI) score slopes for 4 years of follow-up in both cohorts. Additional Cox proportional hazard models were constructed to determine whether the weight changes were associated with the later development of moderate-to-severe symptoms or with a ≥4-point increase in the AUASI score (Olmsted County Study of Urinary Symptoms and Health Status among Men cohort only). RESULTS: Weight changes were not associated with LUTS progression (all P > .05). Additionally, the rate at which the AUASI scores changed did not vary by the weight change. Finally, in the Olmsted County Study of Urinary Symptoms and Health Status among Men cohort, the weight changes were not associated with risk of having a moderate-to-severe AUASI score or a ≥4-point increase in the AUASI score. CONCLUSIONS: Modest weight loss might not prevent the onset or progression of LUTS. However, modest weight gain also might not contribute to changes in LUTS.

Fracture risk in men with prostate cancer: a population-based study.

Fractures are increased among men with prostate cancer, especially those on androgen-deprivation therapy (ADT), but few data are available on men with localized prostate cancer. The purpose of this investigation was to estimate fracture risk among unselected community men with prostate cancer and systematically assess associations with ADT and other risk factors for fracture. In a population-based retrospective cohort study, 742 Olmsted County, MN, men with prostate cancer first diagnosed in 1990-1999 (mean age 68.2 ± 8.9 years) were followed for 6821 person-years. We estimated cumulative fracture incidence, assessed relative risk by standardized incidence ratios, and evaluated risk factors in time-to-fracture regression models. All together, 482 fractures were observed in 258 men (71 per 1000 person-years). Overall fracture risk was elevated 1.9-fold, with an absolute increase in risk of 9%. Relative to rates among community men generally, fracture risk was increased even among men not on ADT but was elevated a further 1.7-fold among ADT-treated compared with untreated men with prostate cancer. The increased risk following various forms of ADT was accounted for mainly by associations with pathologic fractures (14% of all fractures). Among men not on ADT (62% of the cohort), more traditional osteoporosis risk factors were implicated. In both groups, underlying clinical characteristics prompting different treatments (indication bias) may have been partially responsible for the associations seen with specific therapies. To the extent that advanced-stage disease and pathologic fractures account for the excess risk, the effectiveness of fracture prevention among men with prostate cancer may be limited.

Associations between variants in the cyclooxygenase 2 enzyme gene (PTGS2) and development of benign prostate enlargement.

OBJECTIVE: To determine if polymorphisms in the cyclooxygenase 2 (COX-2) enzyme gene (prostaglandin synthase 2; PTGS2) were associated with development of benign prostate enlargement (BPE), and whether associations were modified by use of nonsteroidal anti-inflammatory drugs (NSAIDs). MATERIALS AND METHODS: Participants were men residing in Olmsted County, MN, who were between 40 and 79 years of age in 1990 (N= 356). Prostate volume was measured by transrectal ultrasound and men reported all the medications that they were taking at the time of the examination. Men were followed biennially for 16 years. Ten tagging single nucleotide polymorphisms (SNPs) in the PTGS2 gene were typed using the Illumina GoldenGate(TM) Assay. Associations between SNPs and development of BPE (volume >30 mL) were assessed by Cox proportional hazards models. Models were also stratified by NSAID use. RESULTS: We observed significant associations between four polymorphisms in the PTGS2 gene and development of BPE (all P < 0.05). These associations were not observed among men who used NSAIDs. CONCLUSION: Variants in the PTGS2 gene may increase the risk of prostate enlargement, but the increased risk may be minimized by use of NSAIDs.

Associations between longitudinal changes in serum estrogen, testosterone, and bioavailable testosterone and changes in benign urologic outcomes.

Some men have rapid increases in benign prostatic enlargement and lower urinary tract symptoms (LUTS), and it is not clear how sex steroid hormones contribute to the rates of change in these urologic outcomes. Therefore, the authors conducted a population-based cohort study of 648 men residing in Olmsted County, Minnesota, from 1990 to 2007, to examine associations between baseline sex steroid hormones, the rate of change in these hormones, and the rates of change in LUTS, maximum urinary flow rate, and prostate volume. Annual changes in hormone levels and urologic outcomes were calculated using mixed-effects regression models. Associations between hormone variables and rates of change in urologic outcomes were assessed with linear regression models. Higher baseline estradiol levels and rapid declines in estradiol over time were associated with rapid increases in LUTS and rapid decreases in maximum flow rate. Lower baseline bioavailable testosterone levels and more rapid declines in bioavailable testosterone were associated with more rapid increases in prostate volume. These results suggest that both absolute sex steroid hormone levels and the rates at which the levels change may be important in the development of urologic conditions in aging men.

Estimation of prostate size in community-dwelling men.

OBJECTIVES: To use two population-based samples of prostate cancer-free men to develop and validate a novel multivariable equation for estimating prostate volume (PV). Previous investigators have demonstrated the ability to use serum prostate-specific antigen (PSA) levels to estimate PV in men without prostate cancer; however, the ability of additional clinical variables to further enhance PV estimation in these men remains unclear. METHODS: We applied linear regression modeling to data from an 80% random sample (n = 366) of the baseline cohort from the Olmsted County Study of Urinary Symptoms and Health Status among Men (OCS) to develop an equation for estimating PV in men without prostate cancer. We then evaluated the predictive ability of this equation by comparing estimated and measured PV values in 3 additional validation sets of men. RESULTS: The final linear regression model included PSA, age, and weight as independent predictors of PV. For prediction in baseline OCS men, the multiple correlation coefficients increased from 0.62(PSAalone) to 0.71(fullmodel). In addition, the area under the curve estimates from the receiver operating characteristic curves increased from 0.79(PSAalone) to 0.85(fullmodel) for predicting PV >30 mL. CONCLUSIONS: Our data suggest that PV can be estimated with easily obtained clinical variables. Moreover, we demonstrate that age and weight can be added to PSA level to achieve greater accuracy in predicting PV. This methodology may prove useful for estimating PV in men in settings where costs and practicality preclude the use of imaging techniques.

Statin use and decreased risk of benign prostatic enlargement and lower urinary tract symptoms.

OBJECTIVE: To determine whether statin use is associated with a decreased risk of developing benign prostatic enlargement (BPE) and lower urinary tract symptoms (LUTS). SUBJECTS AND METHODS: We conducted a retrospective, population-based cohort study of 2447 men, 40-79 years of age, residing in Olmsted County, MN, USA, in 1990, and followed these men biennially through 2007. Cox proportional hazard models were used to assess associations between statin use and new onset of moderate/severe LUTS (American Urological Association Symptom Index score >7), a decreased maximum urinary flow rate (<12 mL/s) or BPE (prostate volume >30 mL). RESULTS: Statin use was inversely associated with new onset of LUTS (Hazard ratio (HR) 0.39; 95% confidence interval (CI) 0.31-0.49), a decreased maximum flow rate (HR 0.53; 95% CI 0.34-0.82) and BPE (HR 0.40; 95% CI 0.23-0.69) after adjustment for baseline age and body mass index, diabetes, hypertension, coronary heart disease, smoking, alcohol use, activity level and non-steroidal anti-inflammatory use. The longest duration of statin use was associated with the lowest risk of developing each outcome (all tests for trend: P < 0.001). CONCLUSION: In this study, statin use was associated with a 6.5- to 7-year delay in the new onset of moderate/severe LUTS or BPE. While men typically take statin medications to prevent coronary heart disease events and related outcomes, these data suggest that men who use statins may also receive urologic benefits.

Measures of autonomic nervous system activity and lower urinary tract symptoms.

Autonomic nervous system (ANS) activity may play an important role in the development of lower urinary tract symptoms (LUTS). Men with severe LUTS and men with mild or no LUTS completed the Valsalva maneuver, quantitative sudomotor axon reflex test, tilt-table, and deep breathing tests. There were no differences between men with severe LUTS compared to men with mild or no LUTS (all P values > 0.05). Systemic ANS tests may not be useful in detecting the underlying physiologic changes that lead to LUTS in aging men.

The association between statin use and the diagnosis of prostate cancer in a population based cohort.

PURPOSE: The effect of statin medication use on the risk of prostate cancer is unknown. MATERIALS AND METHODS: We examined data from a longitudinal, population based cohort of 2,447 men between 40 and 79 years old who were followed from 1990 to 2007. Information on statin use was self-reported and obtained by biennial questionnaires. A randomly selected subset of men (634, 26%) completed biennial urological examinations that included serum prostate specific antigen measurements. Information on prostate biopsy and prostate cancer was obtained through review of community medical records. RESULTS: Of 634 statin users 38 (6%) were diagnosed with prostate cancer vs 186 (10%) of 1,813 nonstatin users. Statin use was associated with a decreased risk of undergoing prostate biopsy (HR 0.31; 95% CI 0.24, 0.40), receiving a prostate cancer diagnosis (HR 0.36; 95% CI 0.25, 0.53) and receiving a high grade (Gleason 7 or greater) prostate cancer diagnosis (HR 0.25; 95% CI 0.11, 0.58). Statin use was also associated with a nonsignificantly decreased risk of exceeding a prostate specific antigen threshold of 4.0 ng/ml (HR 0.63; 95% CI 0.35, 1.13). In addition, a longer duration of statin use was associated with a lower risk of these outcomes (all tests for trend p <0.05). CONCLUSIONS: Statin use is associated with a decreased risk of prostate cancer diagnosis. This association may be explained by decreased detection or cancer prevention.