Myeloperoxidase and Prostate volume: A preliminary study.

OBJECTIVES: Oxidative stress is associated with the development of BPH and might be modulated by several factors. Myeloperoxidase (MPO) has recently been observed in prostate tissue. Our goal was to investigate the correlation between MPO and the prostate volume. MATERIAL AND METHODS: Hundred and twenty-one patients (48-70 years) with a filled IPSS were prospectively included. Blood sampling (PSA, testosterone, Angiotensin II (AngII), MPO, Mox-LDL) and transrectal ultrasound of the prostate were performed with total volume (TV) and transitional zone volume (TZ) measurements. For correlation, univariate analyses were depicted by Pearson's coefficient. Multilinear regression analysis used a stepwise backward selection of the explicative variables. RESULTS: In multivariate analysis, the TV was positively correlated to the combination of age and Ang II but negatively to MPO specific activity (Std Coef=-0.272, P=0.004). Significant correlations were confirmed between TZ, age and MPO specific activity but not with Ang II. A negative correlation between TZ and MPO specific activity was also observed (Std Coef=-0.21, P=0.016). No correlation was found with Mox-LDL. CONCLUSIONS: Negative correlation between MPO and prostate volume was observed but careful interpretations may be endorsed and longitudinal study is necessary. It seems relevant to focus on the potential contribution of MPO in the development of prostatic diseases as this enzyme can also promote DNA oxidation. LEVEL OF EVIDENCE: 4.

Intriguing location of myeloperoxidase in the prostate: a preliminary immunohistochemical study.

BACKGROUND: Myeloperoxidase (MPO) is a member of the peroxidase-cyclooxygenase superfamily, which is secreted from stimulated leucocytes at inflammatory sites. It is well known that MPO catalyses oxidation reactions via the release of reactive halogenating and nitrating species and thus induces tissue damage. Several studies have already implicated MPO in the development of neoplasia. Chronic or recurrent prostatic inflammation has long been recognized as having the potential to initiate and promote the development of prostate cancer. The objective was to investigate whether MPO is present in the prostate. METHODS: Human prostate material was obtained from biopsies, transurethral resections of the prostate (TURP), prostatic adenomectomies, and retropubic radical prostatectomies. Twenty-nine slides of normal prostate tissue, benign prostatic hyperplasia (BPH), and prostate cancer were reviewed by a pathologist. Immunohistochemical analysis using MPO-specific human antibody was performed to detect MPO in the prostate tissue. RESULTS: Immunocytohistochemistry showed cellular colocalization of MPO in the secretory epithelial cells of the prostate with staining varying from light to strong intensity. Staining in the glandular apical snouts was often reinforced although staining of basal as well as of luminal glandular cells was also present. CONCLUSIONS: We identified, for the first time, the presence of MPO at the surface of prostatic epithelial cells. In view of the pro-oxidant properties of this enzyme, further research is needed to define whether MPO contributes to the development of prostatic lesions.

[Enuresis: treatments recognized by EBM]. / Enurésie: les traitements soumis à l'épreuve EBM.

Nocturnal enuresis is a frequent pediatric disease which necessitates an appropriate diagnostic and therapeutic approach. In this article, we discuss the epidemiology and physiopathology of this condition. Available evidence suggests that children with monosymptomatic nocturnal enuresis could be treated by bladder advice, the enuresis alarm and/or desmopressin. Therapy resistant cases should be handled by specialist centers.

Erectile dysfunction and cardiovascular diseases.

Erection is a vascular phenomenon under a psychologic control in a hormonal environment. Erectile dysfunction is defined as the inability to obtain and to maintain sufficient erection for satisfactory intercourse. Organic erectile dysfunction results mainly from vascular problems due to atherosclerosis, a process that begins during childhood, and becomes clinically evident from middle age. Endothelial dysfunction is the first step of atherosclerosis. As the endothelial cells recover the sinusoid spaces in the cavernous tissue and because common risk factors for atherosclerosis have been frequently found in patients with erectile dysfunction, it is logical that vascular impotence presents the same pathophysiology of the other vascular diseases. They share a similar pathogenic involvement of nitric oxide pathway leading to impairment of endothelium dependent vasodilatation and structural vascular abnormalities. Circulating markers of endothelial cell damage have been reported in patients with erectile dysfunction while they have not yet presented any other vascular pathology. Endothelial progenitor cells of bone marrow origin that play a role in promoting endothelial repair are also reduced in vascular abnormalities.As penile arteries have the smallest diameter in the vascular network and because atherosclerosis is a systemic disease, erectile dysfunction could be a sentinel symptom of a more generalized vascular pathology. Modifications of reversible causes or risk factors at the base of the pathogenesis of atherosclerosis remain the first approach toward improving endothelial function and associated with chronic exposure to PDE5-I, they could improve or even cure ED and could avoid fatal cardiovascular attacks in the future.

Current approaches to erectile dysfunction and testosterone deficiency.

Androgens are essential for the development of the penis and it is well known that testosterone play a critical role in the physiology of erectile function. From animal studies, testosterone insufficiency disrupts cellular-signaling pathways and induces pathologic alterations in penile tissues leading to erectile dysfunction. In human, the testosterone threshold for maintaining erection is low which explains the reason why some contracted men still have an erection due to the androgens produced by the adrenal gland. Testosterone alone can improve erectile function in hypogonadic patients. Associated with PDE5-I, testosterone supplementation is a treatment for the hypogonadic patients non responders to therapy. The article reviews the different aspects of the testosterone role in the pathophysiology of erection.

Disfunción eréctil y enfermedades cardiovasculares / Erectile dysfunction and cardiovascular diseases

Erection is a vascular phenomenon under a psychologic control in a hormonal environment. Erectile dysfunction is defined as the inability to obtain and to maintain sufficient erection for satisfactory intercourse.Organic erectile dysfunction results mainly from vascular problems due to atherosclerosis, a process that begins during childhood, and becomes clinically evident from middle age.Endothelial dysfunction is the first step of atherosclerosis. As the endothelial cells recover the sinusoid spaces in the cavernous tissue and because common risk factors for atherosclerosis have been frequently found in patients with erectile dysfunction, it is logical that vascular impotence presents the same pathophysiology of the other vascular diseases. They share a similar pathogenic involvement of nitric oxide pathway leading to impairment of endothelium dependent vasodilatation and structural vascular abnormalities. Circulating markers of endothelial cell damage have been reported in patients with erectile dysfunction while they have not yet presented any other vascular pathology.Endothelial progenitor cells of bone marrow origin that play a role in promoting endothelial repair are also reduced in vascular abnormalities.As penile arteries have the smallest diameter in the vascular network and because atherosclerosis is a systemic disease, erectile dysfunction could be a sentinel symptom of a more generalized vascular pathology.Modifications of reversible causes or risk factors at the base of the pathogenesis of atherosclerosis remain the first approach toward improving endothelial function and associated with chronic exposure to PDE5-I, they could improve or even cure ED and could avoid fatal cardiovascular attacks in the future(AU)

OBJETIVO: La erección es un fenómeno bajo control fisiológico en un ambiente hormonal. La disfunción eréctil se define como la incapacidad de obtener y mantener una erección suficiente para una relación sexual satisfactoria.La disfunción eréctil orgánica es principalmente el resultado de problemas vasculares debidos a arterioesclerosis, un proceso que comienza durante la infancia y se hace clínicamente evidente en la edad media.La disfunción endotelial es el primer paso de la arterioesclerosis. Cómo las células endoteliales recubren los espacios sinusoidales en el tejido cavernoso y se han encontrado frecuentemente factores de riesgo de arterioesclerosis en pacientes con disfunción eréctil, es lógico que la impotencia vascular presente la misma fisiopatología de las otras enfermedades vasculares. De forma similar, comparten una participación patogénica de la vía del óxido nítrico que conduce a un empeoramiento de la vasodilatación dependiente del endotelio y a anomalías vasculares estructurales.Se ha publicado la presencia de marcadores circulantes de daño celular endotelial en pacientes con disfunción eréctil cuando todavía no han presentado ninguna otra patología vascular. Las células madre endoteliales con origen en la médula ósea, que juegan un papel en promover la reparación endotelial, también están reducidas en las anomalías vasculares. Cómo las arterias peneanas tienen el calibre más pequeño de la red arterial y la arteriosclerosis es una enfermedad sistémica, la disfunción eréctil podría ser un síntoma centinela de una patología vascular más generalizada.La modificación de causas o factores de riesgo reversibles en la base patogénica de la arteriosclerosis sigue siendo el primer abordaje para mejorar la función endotelial, y asociado con la exposición crónica a inhibidores de la PDE 5 podría mejorar o incluso curar la DE y podría evitar futuros ataques cardiovasculares fatales(AU)

[Decrease ApoB/ApoA-1 ratio and cardiovascular risk improvement: a tadalafil pleiotropic effect? Preliminary study on healthy volunteers]. / Diminution du rapport ApoB/ApoA-1 et amélioration du risque cardiovasculaire : effet pleïotropique du tadalafil ? Etude préliminaire sur volontaires sains.

OBJECTIVES: Recognition of erectile dysfunction (ED) as an early sign of systemic cardiovascular disease offers an opportunity for prevention. Cardiac risk assessment may deserve measurement of Apolipoprotein B/Apolipoprotein A-1 ratio. An elevated ApoB/ApoA-1 ratio is a risk factor for future coronary artery disease. ApoA-1 production, which is recognized as a cardioprotective lipid fraction, is down regulated by NFkappaB activation in vitro. Because inhibition of phosphodiesterases (PDEs) 5, 6 and 9 negatively attenuates NFkappaB translocation/activation, tadalafil, a selective PDE 5 inhibitor used for treatment of ED could present some interesting pleiotropic effects. The objective of this open study is to test the hypothesis that tadalafil treatment could decrease serum ApoB/ApoA-1 ratio. MATERIAL AND METHODS: Ten healthy men without any complain of ED or known cardiovascular risk factors were administered tadalafil 10mg intake on alternate days for 4 weeks. Lipid profile with total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, ApoA-1 and ApoB, was assessed at baseline (T0), after 2weeks (T1), at the end of the treatment period (T2) and after 2weeks of wash-out follow-up (T3). RESULTS: ApoB/ApoA-1 ratio was significantly decreased during treatment (mean+/-SEM, T0: 0.80+/-0.11, T1: 0.64+/-0.06, T2: 0.65+/-0.06; p<0.05) and remained lower after wash-out (T3: 0.67+/-0.05; p=0.08). Serum ApoA-1 (mg/dl) increased but not significantly during the treatment period (15.2+/-8.8, 16.5+/-7.9, 16.9+/-6, 15.3+/-7, p=0.26) and ApoB (mg/dl) significantly decreased (11.7+/-10.8, 10.3+/-8.4, 10.6+/-9.9, 10.2+/-8.6, p=0.03). HDL and LDL cholesterol were unchanged. CONCLUSION: This preliminary study showed the interest of PDE 5 inhibitors to decrease the cardiac risk factor ApoB/ApoA-1 ratio. Randomised controlled studies with longer follow-up are needed to confirm those results.

[Erectile dysfunction and cardiovascular disease in clinical practice]. / Troubles érectiles et maladies cardiovasculaires en pratique clinique.

Erectile dysfunction (ED) is a disorder with a well-established organic basis. ED is considered as a sentinel event for cardiovascular disease (CVD). CVD co-occurs frequently with ED suggesting that each of the condition might be a marker for the other. They share multiple risk factors and the common link is the injury to the endothelial function. Simple and accurate ED assessment tools offer to physicians a quick method to evaluate ED in their patients. Recognition and treatment of CVD risk factors has a major impact in management of CVD and ED. The Princeton Consensus Conference guidelines provides an algorithm for evaluating CVD associated with sexual activity for men with varying degrees of cardiovascular risk. ED can be treated safely and effectively in most men who have concomitant CVD.

[Premature ejaculation]. / Ejaculation précoce.

Ejaculation dysfunction is one of the most common sexual disorders and premature ejaculation is considered the most frequent self-reported male sexual dysfunction. Both central and peripheral neural system is involved in the ejaculatory process. It is centrally mediated by the serotonergic and dopaminergic system. The epidemiology of premature ejaculation (PE) is limited by the lack of consensus definition of lifelong PE and a failure to distinguish lifelong and acquired PE. The diagnosis is based on patient self-report, questionnaires, clinical history and examination findings alone. The treatment uses pharmacologic alone or associated with psychogenic support. Different psychotherapeutic approaches to PE have been described but their efficacies have not been evaluated. A better understanding of PE is undoubtedly necessary to obtain the most efficient results.

Is urinary tract cytology still useful for diagnosis of bladder carcinomas? A large series of 592 bladder washings using a five-category classification of different cytological diagnoses.

BACKGROUND: The aim of this study was to estimate the efficiency of a recent five-category urinary cytological classification. METHODS: A total of 592 bladder washings were fixed immediately with Saccomanno's fixative. All samples were centrifuged in a Hettich cyto-centrifuge. For each sample, the reference standard was the histology when a lesion was present at the time of cystoscopy. A five-category cytological classification was used: negative, suspicious of low (S-Lg) or high (S-Hg) grade neoplasia and consistent with low (Lg) or high (Hg) grade neoplasia. RESULTS: For cytological diagnoses of S-Lg and Lg, sensitivity was 37% and specificity was 95% for the histological diagnosis of low-grade non-invasive urothelial papillary tumour (Lg-UPT), which included papillary urothelial neoplasm of low malignant potential and low-grade urothelial carcinoma. For cytological diagnosis of S-Hg and Hg, sensitivity was 44% for high-grade non-invasive urothelial papillary carcinoma (Hg-UPC), 70% for carcinoma in situ (CIS) and 81% for invasive carcinoma (T1 and higher). Specificity was 99% in each case. Cytological diagnosis of S-Hg or Hg was not found for Lg-UPT (0/59) and no cytological diagnosis of S-Lg or Lg was found for invasive carcinoma, but was seen for Hg-UPC in 10% (3/28) and for CIS in 6% (3/50) of cases. CONCLUSION: Despite the absence of international consensus, the recent five-category cytological classification for urine is accurate for current urological practice.

[Erectile dysfunction, physiologic approach, diagnosis and therapy]. / La dysfonction érctile, approche physiologique, diagnostique et thérapeutique.

Erectile dysfunction is defined as the consistent or recurrent inability to obtain and/or maintain a penile erection sufficient for sexual activity. Erection is a vascular phenomenon under a psychoneurological control and situated in an hormonal environment. A variety of treatment options are available to the clinician including medical, psychological and surgical treatments. The choice of therapy should be based on careful matching of the patient's needs and preferences with the available treatment options.

Erectile dysfunction is associated with a high prevalence of hyperlipidemia and coronary heart disease risk.

OBJECTIVES: Erectile dysfunction (ED) is frequently of vascular origin. An association between ED and ischemic heart disease has been suggested as a consequence of endothelial disease of penile and coronary arteries. The role of serum lipid levels has been demonstrated in coronary heart disease (CHD), but the relationship with ED is poorly documented. We evaluated undiagnosed hyperlipidemia in ED patients and their coronary heart disease risk. METHODS: We prospectively compared a group of patients with ED to matched non-ED patients. Risk factors for ED and CHD were noticed and a serum lipid work up (total cholesterol [TC], triglycerides [TG], HDL-cholesterol [HDL-C], LDL-cholesterol [LDL-C] and TC/HDL-C ratio) was measured. We compared the prevalence of hyperlipidemia in the two groups and its impact as predictor of ED. We calculated the risk to develop CHD in patients with or without ED based upon commonly accepted variables of the Framingham Heart study. RESULTS: 215 patients had ED (mean age 57.6+/-9.6 years) and 100 no ED (mean age 59.7+/-8.3 years). The prevalence of hypercholesterolemia (TC >200 mg/dl or 5.17 mmol/l) was 70.6% vs. 52% in ED and non-ED groups respectively (p=0.06). After exclusion of confounding factors, logistic regression analyses showed HDL-C and TC/HDL-C ratio as significant predictors of ED (p=0.011 and 0.000 respectively). Increased 10-year CHD risk was found in 56.6% in the ED group compared to 32.6% in the control group (p<0.05). The median risk was 12.18% vs. 9.07% respectively with a significant age-related risk (p<001). CONCLUSIONS: Hyperlipidemia is common in ED patients. HDL-C and TC/HDL-C ratio are predictors of ED. These patients have a high risk of later developing CHD. Erectile dysfunction might therefore serve as sentinel event for coronary heart disease.

Intracavernous injection as an option for aging men with erectile dysfunction.

Sexuality remains a vital aspect of life in spite of aging. Advances in impotence research and increased knowledge of the pathophysiology of erection have completely changed the treatment of erectile dysfunction. Before oral therapy, intracavernous injection was considered as the first-line therapy for impotent patients. However, the new simple oral treatment raises the question as to whether intracavernous injection therapy is still a useful tool for treatment of aging men with erectile dysfunction. The efficacy and safety of oral therapy and intracavernous injection are reviewed.

The ageing penis.

Epidemiological reports have demonstrated the determinant role that age plays in the pathophysiological mechanism of an erection. The atherosclerosis of the penis and its ischaemia that occurs with ageing impacts directly on the intracavernous structures and the erectile physiologic function. The effects of testosterone on libido and sexual behaviour are well established but its function in the erectile mechanism remains unclear. In the animals, testosterone deficiency seems to provoke a decrease in smooth muscle content and nitric oxide (NO) production. In human, testosterone seems to affect the central system rather than the peripheral mechanism of an erection. The role of ischaemia and the decrease in testosterone in the mechanism of erectile dysfunction are reviewed.

Smooth muscle pathology and erectile dysfunction.

Penile erection is a vascular phenomenon that results from smooth muscle relaxation, arterial dilation and venous restriction. The atherosclerosis of the penis that occurs with aging causes a decrease in penile oxygen tension. A reduction of smooth muscle cells has been demonstrated in relation with this change in oxygen tension. Changes in the ratio of penile collagen have also been observed and could explain the decrease in penile elasticity and compliance. Chronic ischemia is, therefore, associated with fibrosis but also with nitric oxide (NO)-cyclic guanosine monophosphate. The sensitivity of the alpha-adrenoceptors on the smooth muscle cells increases with aging. All those modifications can explain the prevalence of erectile dysfunction with aging. Low oxygen tension in prostanoid production may also play a role in the mechanism of ischemia-induced cavernosal fibrosis; however, intracavernous injections of prostaglandin E(1) do not seem to modify the intracavernous structures by reducing muscular atrophy. The effects of androgen on libido and sexual behavior are well established, but their role in the human erectile mechanism remains unclear. Several studies performed on animals have demonstrated impacts directly on both the physiological function and the trabecular structure of the corpora cavernosa in rats, dogs and rabbits. However, in humans, no study seems to demonstrate a role of testosterone on muscular atrophy or penile neurologic control. Testosterone treatment alters the human behavior but not penile physiologic processes. Further studies are necessary to explain the real role of testosterone not only on the peripheral mechanism of erection but also on the central control.

Male andropause: myth, reality, and treatment.

A progressive decrease in androgen production is common in aging men. The physiological causes for this phenomenon seem to be multifactorial. The magnitude of the decline in testosterone with age and the prevalence of older men with low testosterone levels have not been well established. The extent to which an age-dependent decline in androgen levels leads to health problems that might affect or alter the quality of life remains under debate. In men older than middle age, total testosterone levels may be misleading because of an increase in sex hormone-binding globulin levels. The mechanism of the age-associated decrease of the endocrine testicular function is also essentially due to primary testicular failure, but important changes occur at the hypothalamopituitary level. The most prominent endocrinological alterations with aging are related to the sex steroids, but others, such as growth hormone, melatonin cortisol, and thyroxine, are also affected. The clinical picture of andropause syndrome is characterized by diminished sexual desire and erectile capacity, decrease in intellectual activity, fatigue, depression, decrease in lean body mass, skin alterations, decrease in body hair, decrease in bone mineral density that results in osteoporosis, and increase in visceral fat and obesity. Current medical treatments for androgen supplementation include oral tablets, intramuscular injections, and scrotal and nonscrotal patches. Unfortunately, none of these preparations mimic the circadian rhythm, even if some of them may approximate the circadian rhythm by dose adjustments. Moreover, the androgen supplementation could have adverse effects on different organs, namely, the liver, lipid profile, cardiovascular disease, prostate, sleep disorders, and emotional behavior. Clinical response is a better guide to dose requirements, regardless of serum testosterone levels. This important field must be actively investigated by the medical, behavioral, and social sciences.

Complete phalloplasty using the free radial forearm flap for correcting micropenis associated with vesical exstrophy.

PURPOSE: We present a new surgical technique for reconstructing the penis in a man with micropenis associated with vesical exstrophy. MATERIALS AND METHODS: A free radial forearm flap was used to create a penis of normal length and diameter. The flap was wrapped around the native micropenis. A penile prosthesis was then inserted in the flap to provide erection. RESULTS: The flap was well vascularized and no skin damage was observed 6 years after reconstruction. The patient achieved sexual intercourse on a regular basis. He is satisfied with the result. CONCLUSIONS: Free transfer of the radial forearm flap may be done in select men with micropenis associated with vesical exstrophy for penile reconstruction. An inflatable prosthesis may be inserted in the flap to provide erection. The results of this technique have remained stable in the long term. This method provides a new tool for phalloplasty in these difficult cases.

Does prostaglandin E1 therapy modify the intracavernous musculature?

PURPOSE: Intracavernous injection of prostaglandin E1 in patients with erectile dysfunction has become widespread. However, to our knowledge long-term side effects on the penile smooth muscles in man have not been documented. We evaluated the histological changes of intracavernous smooth muscle after long-term treatment with prostaglandin E1. MATERIALS AND METHODS: A total of 10 patients with a mean age of 56.5 years (range 46 to 69) underwent biopsy of the corpora before (5) and after (10 in both corpora) prostaglandin E1 treatment. Between 150 and 250 injections during 3 years were performed, and the dosage varied from 5 to 20 microg. Only 1 patient injected prostaglandin E1 on both sides. Staining with hematoxylin and eosin, and immunohistochemical staining with actin anti-actin of intracavernous smooth muscle and its quantification with computerized image analysis were performed. RESULTS: No histological difference was observed with classic staining. A reduction was noted in the percentage of intracavernous smooth muscle after treatment in 2 of 5 patients on the side of injection (before 35% and 41%, and after 19% and 30%, respectively) but there was no difference with the other corpus cavernosum. No difference was observed in the percentage of intracavernous smooth muscle between both corpora in the 5 patients with biopsies performed only after treatment. CONCLUSIONS: Prostaglandin E1 does not seem to alter intracavernous structures.

Erectile dysfunction in the ageing man.

Most studies have shown an increase in the prevalence of erectile dysfunction with ageing. Penile erection is a vascular phenomenon resulting from smooth muscle relaxation, arterial dilatation and venous restriction. The atherosclerosis of the penis that occurs with ageing causes a decrease in penile oxygen tension. This change in oxygen tension impacts directly upon both the physiologic function and the trabecular structure of the corpora cavernosa. Chronic ischaemia of the penis is associated with fibrosis of smooth muscle fibres and with endothelial and neuronal NO/cGMP pathways. The effects of androgens on libido and sexual behaviour are well established but their role in the erectile mechanism remains unclear. The histologic and haemodynamic causes responsible for the erectile decline in the ageing man are reviewed.

[New treatments for impotence]. / Les nouveaux traitements de l'impuissance.

The development of new oral drugs and the poor results of the reconstructive vascular surgery has modified the therapeutical approach of the impotent patient. The doctor has to be aware of these changes in the management of impotence.