Rural vs. urban disparities in association with lower urinary tract symptoms and benign prostatic hyperplasia in ageing men, NHANES 2001-2008.

OBJECTIVE: The objective of this study was to investigate rural/urban and socio-demographic disparities in lower urinary tract symptoms and benign prostatic hyperplasia (LUTS/BPH) in a nationally representative population of men. METHODS: Data on men age ≥40 years (N = 4,492) in the 2001-2008 National Health and Nutrition Examination Surveys were analysed. Self-report of physician-diagnosed enlarged prostate and/or BPH medication use defined recognised LUTS/BPH. Urinary symptoms without BPH diagnosis/medications defined unrecognised LUTS/BPH. Rural-Urban Commuting Area Codes assessed urbanisation. Unadjusted and multivariable associations (odds ratios (OR)) between LUTS/BPH and covariates were calculated using logistic regression. RESULTS: Recognised and unrecognised LUTS/BPH weighted-prevalence estimates were 16.5% and 9.6%. There were no significant associations between LUTS/BPH and rural/urban status. Significant predisposing factors for increased adjusted odds of recognised and unrecognised LUTS/BPH included age, hypertension (OR=1.4;1.4), analgesic use (OR=1.4;1.4) and PSA level >4 ng/mL (OR=2.3;1.9) when adjusted for rural/urban status, race, education, income, alcohol, health insurance, health care and proton pump inhibitor (PPI) use (all p ≤ 0.1). Restricting to urban men only (N = 3,371), healthcare use (≥4visits/year) and PPI's increased adjusted odds of recognised LUTS/BPH (OR=2.0;1.6); no health insurance and

Influence of Trifloxystrobin on Primary Inoculum and Progression of Scab Epidemics on Stone Fruit.

The ability of the QoI fungicide trifloxystrobin to reduce production of conidia by Fusicladium carpophilum on twig lesions was quantitatively assessed over a 3-year period from 2005 through 2007. Four annual treatment programs, consisting of two consecutive trifloxystrobin applications at pink + bloom, bloom + petal fall, and petal fall + shuck-split, plus a single application timing at petal fall, were examined in a 'Redgold' nectarine orchard harboring high levels of overwintering scab lesions. Sporulation potential, the ability of twig lesions to produce conidia under optimum environmental conditions, was subsequently assessed five to six times during each spring and early summer. In each year of the study, all four treatments significantly reduced the area under the sporulation curve or peak sporulation. The petal fall + shuck-split program provided the greatest antisporulant activity, reducing conidia production at peak sporulation by 82 to 92%. Furthermore, examination of results over the 3-year period showed that the programs significantly slowed the annual rate of increase in peak sporulation; however, none of the programs completely halted or caused a decline in the annual rate. Although no fungicide was applied after the treatment programs, results from fruit disease assessments showed that these programs, applied as much as 3 months earlier, significantly reduced disease incidence and, in particular, disease severity. A comparison of four QoI fungicides in 2008 indicated that trifloxystrobin and azoxystrobin provided the most control of fruit scab, while pyraclostrobin + boscalid and fluoxastrobin yielded minimal or no benefit. Results of this study demonstrate that certain QoI fungicides, in particular trifloxystrobin and azoxystrobin, can probably improve the efficacy of current protectant programs used for peach scab control by providing season-long control of F. carpophilum sporulation on twig lesions. Such program enhancement may be critical when orchards have high inoculum levels and/or environmental conditions are very favorable to disease development.

The assessment of vascular risk in men with erectile dysfunction: the role of the cardiologist and general physician.

Erectile dysfunction (ED) and cardiovascular disease (CVD) share risk factors and frequently coexist, with endothelial dysfunction believed to be the pathophysiologic link. ED is common, affecting more than 70% of men with known CVD. In addition, clinical studies have demonstrated that ED in men with no known CVD often precedes a CVD event by 2-5 years. ED severity has been correlated with increasing plaque burden in patients with coronary artery disease. ED is an independent marker of increased CVD risk including all-cause and especially CVD mortality, particularly in men aged 30-60 years. Thus, ED identifies a window of opportunity for CVD risk mitigation. We recommend that a thorough history, physical exam (including visceral adiposity), assessment of ED severity and duration and evaluation including fasting plasma glucose, lipids, resting electrocardiogram, family history, lifestyle factors, serum creatinine (estimated glomerular filtration rate) and albumin:creatinine ratio, and determination of the presence or absence of the metabolic syndrome be performed to characterise cardiovascular risk in all men with ED. Assessment of testosterone levels should also be considered and biomarkers may help to further quantify risk, even though their roles in development of CVD have not been firmly established. Finally, we recommend that a question about ED be included in assessment of CVD risk in all men and be added to CVD risk assessment guidelines.

Modeling sporulation of Fusicladium carpophilum on nectarine twig lesions: relative humidity and temperature effects.

The production of conidia by Fusicladium carpophilum on twig lesions was quantitatively modeled as a function of temperature and duration of high relative humidity. During peak sporulation periods in 2007, 2008, and 2009, 1-year-old twigs bearing abundant overwintering lesions were removed from a heavily infected 'Redgold' nectarine orchard, placed in trays at high relative humidity (>95%), and incubated at eight constant temperatures for seven durations, resulting in a factorial design of 56 treatment combinations. Conidia numbers were estimated with a hemacytometer. Results from a six-stage modeling process indicated that, at any given temperature, spore production during high relative humidity periods increased in a monomolecular- to Gompertz-like pattern. The Richards model, with shape parameters of 0.79 to 0.90, was found to provide the best overall fit. When the asymptote and rate parameters were derived as functions of temperature using Gaussian and quadratic models, respectively, the duration of high relative humidity and temperature described 90 to 94% of the variation in conidia production. Predictions of the final models were highly correlated with observed levels of sporulation (r > 0.94; P < 0.0001), indicating an excellent fit to the data. The optimum temperature for sporulation, based on fitting a Gaussian model to the maximum sporulation levels at each temperature, was 17.9 to 20.2°C, with an overall average of 18.8°C. The derived models give a quantitative description of sporulation by F. carpophilum and may have potential use in simulators and forecasting systems.

Urinary bladder-urethral sphincter dysfunction in mice with targeted disruption of neuronal nitric oxide synthase models idiopathic voiding disorders in humans.

Idiopathic voiding disorders affect up to 10-15% of men and women. We describe bladder abnormalities in mice with targeted deletion of the gene for neuronal nitric oxide synthase which model the clinical disorders. The mice possess hypertrophic dilated bladders and dysfunctional urinary outlets which do not relax in response to electrical field stimulation or L-arginine. The mice also display increased urinary frequency.

Ejaculatory abnormalities in mice with targeted disruption of the gene for heme oxygenase-2.

Nitric oxide (NO) is well established as a neurotransmitter in the central and peripheral nervous systems. More recently, another gas, carbon monoxide (CO) has also been implicated in neurotransmission. In the nervous system CO is formed by a subtype of heme oxygenase (HO) designated HO2. HO2 is localized to discrete neuronal populations in the brain resembling localizations of soluble guanylyl cyclase, which is activated by CO. CO may also function in the peripheral autonomic nervous system, in conjunction with NO. The majority of ganglia in the myenteric plexus possess both HO2 and neuronal NO synthase (NOS). Defects in myenteric plexus neurotransmission occur both in mice with targeted deletion of genes for HO2 and neuronal NOS. HO2 also occurs in other autonomic ganglia including the petrosal, superior cervical and nodose ganglia. Neuronal NOS is localized to neurons regulating male reproductive behavior, such as penile erection, and NOS inhibitors prevent erection. Because of the other parallels between NO and CO, we speculated that CO may play a role in male reproductive behavior. In the present study we describe HO2 localization in neuronal structures regulating copulatory reflexes. Reflex activity of the bulbospongiosus muscle, which mediates ejaculation and ejaculatory behavior, is markedly diminished in mice with targeted deletion of the gene for HO2 (HO2-).

Effect of QoI Fungicides on Colonization and Sporulation of Monilinia fructicola on Peach Fruit and Blossom Blight Cankers.

Three studies were conducted to examine the curative activity of azoxystrobin, trifloxystrobin, and pyraclostrobin + boscalid against Monilinia fructicola, causal agent of brown rot on peach. In the first study, 'Autumnglo' peach trees were treated with each of the three fungicides both before and after fruit inoculation. In the second study, the effects of fungicide active ingredient, rate/volume, and inoculation timing were examined on inoculated 'Suncrest' peach fruit. Results of these studies showed that sporulating area, on average across all treatments, was reduced by 15.9, 42.4, and 0.4% for azoxystrobin, trifloxystrobin, and pyraclostrobin + boscalid, respectively. In any single treatment, trifloxystrobin provided the greatest benefit with two consecutive sprays, reducing sporulating area by 53 to 60%. In contrast to sporulation activity, the three fungicides exhibited less of an inhibitory effect on fruit colonization. When applied at maximum labeled rates in the various treatments, azoxystrobin, trifloxystrobin, and pyraclostrobin + boscalid reduced colony growth, on average, by 12.3, 7.5, and 7.4%, respectively. Because the pathogen was inoculated into the mesocarp, this low level of activity against colonization may be due to a lack of deeper systemic movement of the fungicides into fruit tissue. In the final study, the three fungicides were examined for their antisporulant activity on blossom blight twig cankers. Unlike results observed on fruit, significant reductions in spore production on cankers were observed for all three fungicides. Azoxystrobin, trifloxystrobin, and pyraclostrobin + boscalid provided 56, 71, and 53% reductions, respectively, in the number of conidia produced per unit canker length. Overall results of these studies indicated that quinone outside inhibitor fungicides, in addition to their known protectant activity, also possess varying levels of curative activity against M. fructicola. In particular, trifloxystrobin demonstrated good antisporulant activity on both fruit infections and cankers.

Nitric oxide: a physiologic mediator of penile erection.

Nitric oxide (NO) is a cytotoxic agent of macrophages, a messenger molecule of neurons, and a vasodilator produced by endothelial cells. NO synthase, the synthetic enzyme for NO, was localized to rat penile neurons innervating the corpora cavernosa and to neuronal plexuses in the adventitial layer of penile arteries. Small doses of NO synthase inhibitors abolished electrophysiologically induced penile erections. These results establish NO as a physiologic mediator of erectile function.

Testosterone replacement in transgenic sickle cell mice controls priapic activity and upregulates PDE5 expression and eNOS activity in the penis.

Sickle cell disease (SCD)-associated priapism is characterized by decreased nitric oxide (NO) signaling and downregulated phosphodiesterase (PDE)5 protein expression and activity in the penis. Priapism is also associated with testosterone deficiency, but molecular mechanisms underlying testosterone effects in the penis in SCD are not known. Given the critical role of androgens in erection physiology and NO synthase (NOS)/PDE5 expression, we hypothesized that testosterone replacement to eugonadal testosterone levels reduces priapism by reversing impaired endothelial (e)NOS activity and molecular abnormalities involving PDE5. Adult male transgenic Berkeley sickle cell (Sickle) and wild-type (WT) mice were implanted with testosterone pellets, which release 1.2 µg testosterone/day for 21 days, or vehicle. After 21 days, animals underwent erectile function assessment followed by collection of blood for serum testosterone measurements, penes for molecular analysis, and seminal vesicles as testosterone-responsive tissue. Serum testosterone levels were measured by radioimmunoassay; protein expressions of PDE5, α-smooth muscle actin, eNOS and nNOS, and phosphorylation of PDE5 at Ser-92, eNOS at Ser-1177, neuronal (n) NOS at Ser-1412, and Akt at Ser-473 were measured by Western blot in penile tissue. Testosterone treatment reversed downregulated serum testosterone levels and increased (p < 0.05) the weight of seminal vesicles in Sickle mice to levels comparable to that of WT mice, indicating restored testosterone levels in Sickle mice. Testosterone treatment reduced (p < 0.05) prolonged detumescence in Sickle mice and normalized downregulated P-PDE5 (Ser-92), PDE5, P-eNOS (Ser-1177), and P-Akt (Ser-473) protein expressions in the Sickle mouse penis. Testosterone treatment did not affect P-nNOS (Ser-1412), eNOS, nNOS, or α-smooth muscle actin protein expressions in the Sickle mouse penis. In conclusion, in the mouse model of human SCD, increasing testosterone to eugonadal levels reduced priapic activity and reversed impaired Akt/eNOS activity and PDE5 protein expression in the penis.

Endothelial dysfunction in diabetic erectile dysfunction.

Erectile dysfunction (ED) is highly prevalent in diabetes mellitus. Pathophysiological mechanisms underlying diabetes-associated ED are in large part due to endothelial dysfunction, which functionally refers to the inability of the endothelium to produce vasorelaxing messengers and to maintain vasodilation and vascular homeostasis. The precise mechanisms leading to endothelial dysfunction in the diabetic vasculature, including the penis, are not yet fully understood. Hyperglycemia affects endothelial nitric oxide synthase activity and nitric oxide production/bioavailability, nitric oxide-independent relaxing factors, oxidative stress, production and/or action of hormones, growth factors and/or cytokines, and generation and activity of opposing vasoconstrictors. Considering recent advances in the field of vascular biology and diabetes, the emphasis in this review is placed on the mechanisms of hyperglycemia-induced endothelial dysfunction in the pathophysiology of diabetes-associated ED.

Constitutive NOS uncoupling and NADPH oxidase upregulation in the penis of type 2 diabetic men with erectile dysfunction.

Erectile dysfunction (ED) associated with type 2 diabetes mellitus (T2DM) involves dysfunctional nitric oxide (NO) signaling and increased oxidative stress in the penis. However, the mechanisms of endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) dysregulation, and the sources of oxidative stress, are not well defined, particularly at the human level. The objective of this study was to define whether uncoupled eNOS and nNOS, and NADPH oxidase upregulation, contribute to the pathogenesis of ED in T2DM men. Penile erectile tissue was obtained from 9 T2DM patients with ED who underwent penile prosthesis surgery for ED, and from six control patients without T2DM or ED who underwent penectomy for penile cancer. The dimer-to-monomer protein expression ratio, an indicator of uncoupling for both eNOS and nNOS, total protein expressions of eNOS and nNOS, as well as protein expressions of NADPH oxidase catalytic subunit gp91phox (an enzymatic source of oxidative stress) and 4-hydroxy-2-nonenal [4-HNE] and nitrotyrosine (markers of oxidative stress) were measured by western blot in this tissue. In the erectile tissue of T2DM men, eNOS and nNOS uncoupling and protein expressions of NADPH oxidase subunit gp91phox, 4-HNE- and nitrotyrosine-modified proteins were significantly (p < 0.05) increased compared to control values. Total eNOS and nNOS protein expressions were not significantly different between the groups. In conclusion, mechanisms of T2DM-associated ED in the human penis may involve uncoupled eNOS and nNOS and NADPH oxidase upregulation. Our description of molecular factors contributing to the pathogenesis of T2DM-associated ED at the human level is relevant to advancing clinically therapeutic approaches to restore erectile function in T2DM patients.

Mechanistic link between erectile dysfunction and systemic endothelial dysfunction in type 2 diabetic rats.

Men with type 2 diabetes mellitus (T2DM) and erectile dysfunction (ED) have greater risk of cardiovascular events than T2DM men without ED, suggesting ED as a predictor of cardiovascular events in diabetic men. However, molecular mechanisms underlying endothelial dysfunction in the diabetic penis explaining these clinical observations are not known. We evaluated whether the temporal relationship between ED and endothelial dysfunction in the systemic vasculature in T2DM involves earlier redox imbalance and endothelial nitric oxidase synthase (eNOS) dysfunction in the penis than in the systemic vasculature, such as the carotid artery. Rats were rendered T2DM by high-fat diet for 2 weeks, followed by an injection with low-dose streptozotocin. After 3 weeks, erectile function (intracavernosal pressure) was measured and penes and carotid arteries were collected for molecular analyses of eNOS uncoupling, protein S-glutathionylation, oxidative stress (4-hydroxy-2-nonenal, 4-HNE), protein expression of NADPH oxidase subunit gp91(phox) , endothelium-dependent vasodilation in the carotid artery, and non-adrenergic, non-cholinergic (NANC)-mediated cavernosal relaxation. Erectile response to electrical stimulation of the cavernous nerve and NANC-mediated cavernosal relaxation was decreased (p < 0.05), while relaxation of the carotid artery to acetylcholine was not impaired in T2DM rats. eNOS monomerization, protein expressions of 4-HNE and gp91(phox) , and protein S-glutathionylation, were increased (p < 0.05) in the penis, but not in the carotid artery, of T2DM compared to non-diabetic rats. In conclusion, redox imbalance, increased oxidative stress by NADPH oxidase, and eNOS uncoupling, occur early in T2DM in the penis, but not in the carotid artery. These molecular changes contribute to T2DM ED, while vascular function in the systemic vasculature remains preserved.

Pharmacotherapeutic management of erectile dysfunction.

Erectile dysfunction is a common condition in aging men and significantly affects their quality of life and interpersonal relationships. Its prevalence and incidence are associated with aging, lifestyle factors and cardiovascular comorbidities. Preoccupation with male virility has been present for centuries, and a wide variety of herbs and potions have been used to treat any sexual deficiencies. Recent major advances in understanding of erectile physiology and pathophysiology led to development of currently available systemic and local pharmacotherapies. They are designed to work either centrally or peripherally and to either suppress anti-erectile mechanisms, enhance the pro-erectile ones or influence both. Since all the current formulations have variable safety and efficacy profiles, the search for highly specific, simple, convenient and clinically effective impotence treatments or prophylactics continues.

Inflatable penile prosthesis technique and outcomes after radial forearm free flap neophalloplasty.

The aim of this study was to describe the technical aspects and short-term outcomes of inflatable penile prosthesis (IPP) implantation after neophallus reconstruction at a single institution. Nine men with previously constructed radial forearm neophalli underwent IPP implantation. The etiologies of their penile anomaly were bladder exstrophy complex in five, disorder of sexual differentiation in two and genital obliteration secondary to ballistic trauma in two. Median follow-up was 9.6 months (range 1.5-139.7). The records for these patients were retrospectively reviewed and outcomes recorded. Mean age was 23.6 (range 18-31) years, and mean time interval from neophalloplasty to IPP implantation was 22.1 months (range 3-48). In all cases, 3-piece IPPs were employed, with eight of patients having one cylinder implanted in the native corporal body and extending into the neophallus. Mean surgical time was 222 min (range 142-409). Median length of implanted device was 22 cm. No intraoperative complications were observed. At the most recent follow-up, six patients (66.7%) had functional devices, with acceptable surgical outcomes. Three patients (33.3%) sustained device infections, and three (33.3%) sustained cylinder erosion. In three patients in whom neo-tunica albuginea were fashioned by ensheathing the cylinder with allograft human dermal tissue matrix, no erosions occurred. One patient underwent two revisions, the first for the associated erosion and infection and the second for genital pain, and was left with a semi-rigid prosthesis. IPP implantation affords the best opportunity for functionality for patients with a radial forearm free flap neophallus. Caution must be taken to ensure viability of the neophallus intraoperatively, and protocols to minimize the risk of infection should be followed. Fashioning neo-tunica albuginea using graft material may reduce risk of erosion.

Nitric oxide control of lower genitourinary tract functions: a review.

It is apparent that evolving concepts of the regulatory basis for functions in the pelvis must take into account the role exerted by nitric oxide. A recently characterized messenger molecule, nitric oxide has been associated with numerous physiologic processes. Intense investigations of this molecule have extended its importance to several genitourinary functions. Penile erection, micturition, peristalsis of the male excurrent duct system, contractile properties of the prostate, and lumbosacral spinal cord neurotransmission are all functions that may transpire under some degree of control by nitric oxide. Impotence, urinary obstruction, or ejaculatory problems, in turn, may represent alterations of nitric oxide production or action. The strategic manipulation of nitric oxide or its mechanism of action, possibly by pharmacologic means, may restore or produce desired functional effects. These possibilities, therefore, suggest that the advancing knowledge of nitric oxide in the genitourinary tract may be of enormous clinical value in the future.

Spectrum of differentiation in pediatric epithelial tumors of kidney: report of two cases.

Two unusual presentations of childhood renal cell epithelial tumors including one whose unique clinical manifestation was polycythemia are described. One was a renal cell carcinoma which was so poorly differentiated that ancillary histopathologic techniques were necessary to arrive at the correct diagnosis. The other case represented the opposite extreme being so well-differentiated as to raise the differential diagnosis of renal cell carcinoma versus renal cell adenoma with blastemal areas. These case studies exemplify the practical role for specialized histopathologic techniques in diagnosing pediatric renal tumors, which may not be feasibly or even accurately categorized into known renal tumor types using routine diagnostic methods.

Adenocarcinoma of urinary bladder: classification and management.

Adenocarcinoma of the urinary bladder is an uncommon, often aggressive urologic cancer. In an attempt to classify and define management of this tumor, 28 patients with vesical adenocarcinoma were studied. Excluded were patients with mixed transitional cell carcinoma and adenocarcinoma. Three major classes of tumor were identified: primary vesical adenocarcinoma, urachal adenocarcinoma, and extravesical adenocarcinoma involving the bladder. Signet ring cell tumors appeared to behave more aggressively than other cell types. Radical surgery was the most effective treatment.

Effects of nitric oxide on human and canine prostates.

OBJECTIVES: To determine whether nitric oxide (NO) is a mediator of prostatic smooth muscle activity. METHODS: Pharmacologic experiments using electrical field stimulation (EFS) were performed on strips of human and canine prostate. RESULTS: EFS alone elicited frequency-dependent contractions in preparations of human and canine prostates. The greatest contractile activity was achieved at 30 Hz. In the presence of 10(-5) M guanethidine (GUA) and 2 x 10(-6) M atropine (ATR), EFS elicited relaxation of canine prostate strips relative to baseline tension. A weak biphasic response consisting of initial relaxation and subsequent contraction relative to baseline tension was observed in the human prostate strips exposed to similar conditions. The smooth muscle activity observed in the presence of GUA plus ATR was attributed to nonadrenergic, noncholinergic (NANC) nerve transmission. 10(-4) M L-NG-nitroarginine methylester (NAME) significantly increased EFS-elicited NANC smooth muscle activity both in human and canine prostates. L-arginine, 10(-2) M, reversed the effect of L-NAME in human and canine prostates. Sodium nitroprusside, 10(-4) M, a donor of NO, caused relaxation of both human and canine prostates. The mean magnitude of the relaxant response/cross-sectional area in human prostate (2.64 +/- 0.4 g/cm2) was significantly greater than in the canine prostate (1.09 +/- 0.17 g/cm2) (P < 0.005). CONCLUSIONS: These results provide compelling evidence that NO plays a role in mediating contractile function of human and canine prostates.

Evaluation of erectile function in men with sickle cell disease.

OBJECTIVES: To evaluate and characterize erectile manifestations associated with sickle cell disease using nocturnal penile tumescence testing with polysomnography (NPT/PSG) and magnetic resonance imaging (MRI) of the penis. METHODS: Six variably potent men with sickle cell disease, of whom 5 reported a history of priapism, underwent comprehensive evaluations of erectile function. Evaluations involved a medical history and physical examination with completion of priapism and sexual function questionnaires, followed by NPT/PSG and MRI of the penis. RESULTS: Many different erectile abnormalities were identified in this group using NPT/PSG, although nocturnal erection durations as well as detumescence times were uniformly prolonged. Various axial rigidity measurements were obtained, which correlated fairly well with individual reports of erectile function. MRI findings ranged from normal corporeal anatomy to corporeal destruction with intracorporeal fibrosis and hemosiderin deposition. CONCLUSIONS: In sickle cell disease, the erectile dysfunction that commonly occurs may be markedly different among men with this disease and may not always be predicted on the basis of clinical history of priapism. Generally, clinical assessments of erectile function may be derived from clinical histories and physical examinations. NPT/PSG and MRI of the penis are in accord with these assessments, obviating their routine use, although they may be valuable management adjuncts in certain situations.