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OBJECTIVES: To evaluate the effects of testosterone-replacement therapy (TRT) on prostate health indicators in hypogonadal men, including rates of prostate cancer diagnoses, changes in prostate-specific antigen (PSA) levels and lower urinary tract symptoms (LUTS) over time.PATIENTS AND METHODS: The Registry of Hypogonadism in Men (RHYME) is a multi-national patient registry of treated and untreated, newly-diagnosed hypogonadal men (n = 999). Follow-up assessments were performed at 3-6, 12, 24, and 36 months. Baseline and follow-up data collection included medical history, physical examination, blood sampling, and patient questionnaires. Prostate biopsies underwent blinded independent adjudication for the presence and severity of prostate cancer; PSA and testosterone levels were measured via local and central laboratory assays; and LUTS severity was assessed via the International Prostate Symptom Score (IPSS). Incidence rates per 100 000 person-years were calculated. Longitudinal mixed models were used to assess effects of testosterone on PSA levels and IPSS.RESULTS: Of the 999 men with clinically diagnosed hypogonadism (HG), 750 (75%) initiated TRT, contributing 23 900 person-months of exposure. The mean testosterone levels increased from 8.3 to 15.4 nmol/L in treated men, compared to only a slight increase from 9.4 to 11.3 nmol/L in untreated men. In all, 55 biopsies were performed for suspected prostate cancer, and 12 non-cancer related biopsies were performed for other reasons. Overall, the proportion of positive biopsies was nearly identical in men on TRT (37.5%) compared to those not on TRT (37.0%) over the course of the study. There were no differences in PSA levels, total IPSS, or the IPSS obstructive sub-scale score by TRT status. Lower IPSS irritative sub-scale scores were reported in treated compared to untreated men.CONCLUSIONS: Results support prostate safety of TRT in newly diagnosed men with HG.

The category HopfR of Hopf algebras over a commutative unital ring R is analyzed with respect to its categorical properties. The main results are: (1) For every ring R the category HopfR is locally presentable, it is coreflective in the category of bialgebras over R, over every R-algebra there exists a cofree Hopf algebra. (2) If, in addition, R is absoluty flat, then HopfR is reflective in the category of bialgebras as well, and there exists a free Hopf algebra over every R-coalgebra. Similar results are obtained for relevant subcategories of HopfR. Moreover it is shown that, for every commutative unital ring R, the so-called "dual algebra functor" has a left adjoint and that, more generally, universal measuring coalgebras exist.Keywords: Hopf algebras, *bialgebras, limits, colimits, free Hopf algebras, cofree Hopf algebras, Hopf envelope, universal measuring coalgebra.

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In der Therapie der erektilen Dysfunktion (ED) der nachsten 3–5 Jahre werden weiterhin Substanzen dominieren, welche den Arginin-NO-Guanylatzyklase-cGMP-PDE-5-Mechanismus attackieren und somit die intrazellulare cGMP-Konzentration erhohen. Viel versprechende Alternativen zu den PDE-5-Inhibitoren stellen Guanylatzyklase Aktivatoren und Rho-Kinase Inhibitoren dar, evtl. im Dualprinzip mit einem PDE-5-Inhibitor. Vom zentralen Ansatzpunkt her erscheint die intranasale Anwendung des Melanocortin-Agonisten PT-141 (Melanotan II) erfolgversprechend. Da von den meisten Paaren eine Terminierung sexueller Aktivitaten nicht gewunscht ist, wird die zukunftige ED-Therapie hin zu Substanzen mit klinischer Wirksamkeit uber 1–2 Tage oder aber zur taglich nachtlichen Anwendung niedrig dosierter Substanzen gehen, welche zur nachtlichen Reoxygenierung der Schwellkorper und damit einer Funktionsverbesserung fuhren. Die damit einhergehende Erhohung der cGMP-Spiegel und Verbesserung der Endothelfunktion verspricht auch Benefite bei weiteren kardiovaskularen Erkrankungen und bei LUTS.

We report two cases of acute hepatitis E. The first case is a 21-year-old male who had returned two weeks earlier from a three-month journey to India. He was admitted into our clinic with nausea, stomach pain, vomiting, scleral icterus and stool discoloration. After excluding other possible causes of the symptoms, we made the diagnosis by testing for antibodies by EIA. No treatment was initiated and despite a temporary increase of the icterus, the patient returned to a normal state of health. The second case is a native of India who has lived in Germany for ten years. He returned from a two-week visit to India with fever, nausea and malaise. In follow-up, he was anicteric, and a temporary thrombocytopenia was detected. He was treated symptomatically. and recovered within a few days. The patient had a secondary diagnosis of sinusitis, which was resolved with antibiotics. In spite of a large spectrum of diagnostic possibilities, a part of the liver diseases cannot be etiologically clarified. Following travel to India and other endemic regions, hepatitis E should be considered in the differential diagnosis. The course of hepatitis E is usually benign, further diagnostic studies are rarely needed, and the treatment is usually symptomatic.

OBJECTIVE: To evaluate the reliability, efficacy, and safety of vardenafil, 10 mg, for patients with erectile dysfunction. PATIENTS AND METHODS: Vardenafil-naive patients completed a 4-week treatment-free run-in phase and a 1-week single-dose vardenafil (10 mg) open-label challenge phase. Responders to vardenafil in the challenge phase were randomized to 12 weeks of double-blind, fixed-dose treatment with vardenafil at 10 mg or placebo. Diary responses to Sexual Encounter Profile (SEP) questions about erections and attempts at sexual activity were collected after 4, 8, and 12 weeks of randomized treatment. Adverse events were monitored throughout the study. RESULTS: During the open-label challenge phase, the proportions of patients with a first-time success for penetration (SEP2) and maintenance of erection (SEP3) were 87% and 74%, respectively. Of 600 patients challenged with a single dose of vardenafil at 10 mg, 260 were randomized to vardenafil and 263 to placebo. During the double-blind phase, the reliability of penetration and maintenance rates for patients successful during the challenge phase were significantly greater with vardenafil compared with placebo (83.4% vs 55.8% [SEP2] and 76.6% vs 42.1% [SEP3], respectively). At week 12, patients in the vardenafil group had a consistently higher least squares mean (SE) on the erectile function domain score of the International Index of Erectile Function than patients in the placebo group (23.5 [0.4] vs 15.8 [0.4], respectively [last observation carried forward]) and a greater proportion of positive responses to the Global Assessment Question (80.8% vs 32.3%, respectively [last observation carried forward]) at each assessment (P

APPENDIX: INVESTIGATORS BY PARTICIPATING SITE: A Dignass: Markus-Krankenhaus, Frankfurt, Germany; H Lochs: Campus Charité Mitte Berlin, Germany; H Porst: Städtisches Klinikum Dresden, Germany; G von Boyen: Universitäts-klinikum Ulm, Ulm, Germany; A Raedler: Asklepios Westklinikum, Hamburg, Germany; M Reinshagen: Städtisches Klinikum, Braunschweig, Germany; B Bonaz: Albert Michallon Hospital, Grenoble, France; W Vogel: LKH Univ.-Klinik, Innsbruck, Austria; S Vavricka: Universita¨tsspital Zürich, Switzerland; C Felley: CHUV Lausanne, Switzerland; F Seibold: Inselspital, Bern, Switzerland; C Ciacci: Università Federico II, Napoli, Italy; M Vecchi: Policlinico S. Donato Milanese, Italy; R Sablich: Ospedale S. Maria degli Angeli, Pordenone, Italy; A Malesci: Clinico Humanitas Rozzano, Milano, Italy; M Cottone: Ospedale Cervello Palermo, Italy; G Riegler: Policlinico II, Università di Napoli, Napoli, Italy; G Minoli: Ospedale Valduce, Como, Italy; A Lanzini: Spedali Civili 1, Brescia, Italy; X Hébuterne: Hôpital de l'Archet 2, Nice, France; P Premchand: Queen's Hospital, Romford, United Kingdom; K Douglas: West of Scotland Cancer Centre, Glasgow, United Kingdom; J Rhodes: Royal Liverpool Hospital, Liverpool, United Kingdom; L Castro-Larsa: Hospital Virgen Macarena, Seville, Spain; A Rodriguez- Pérez: Hospital Universitario de Salamanca, Salamanca, Spain; A Pukitis: Paul Stradins Clinical University Hospital, Riga, Latvia; A Kilander: Sahlgrenska Universitetssjukhuset, Gothenberg, Sweden; A Lapidus: Ersta Sjukhus, Stockholm, Sweden; A Makin: Manchester Royal Infirmary, Manchester, United Kingdom; M H Vatn: Rikshospitalet, Oslo, Norway; R Løfberg: Sophia Hemmet Hospital, Stockholm, Sweden; Y Bouhnik: Hopital Beaujon, Clichy, France; B Flourié: Centre Hospitalier Lyon Sud, Pierre-Bénite, France; W Kruis: Ev. Krankenhaus, Köln-Kalk, Germany; G Bommelaer: CHU HOTEL-Dieu, Clermont-Ferrand, France; A Thillainayagam: Charing Cross Hospital, London, United Kingdom; A Sturm and DC Baumgart: Charité Campus Virchov-Klinikum, Berlin, Germany; V Annese: CSS-IRCCS Hospital, San Giovanni Rotondo, Italy; A Indriolo: Ospedali Reuniti, Bergamo, Italy; A Eriksson: Sahlgrenska University Hospital ⁄ East Hospital, Gothenberg, Sweden; S Vavricka: Universitätsspital, Basel, Switzerland; J Emmrich: Universität Rostock, Rostock, Germany.; International audience; BACKGROUND: Ulcerative colitis is characterized by leucocyte infiltration into the colonic mucosa. Granulocyte-monocyte apheresis depletes these cells. AIM: To assess the non-inferiority of 5-10 apheresis treatments in patients with steroid-dependent or steroid-refractory ulcerative colitis. METHODS: A total of 196 adults with moderate-severe ulcerative colitis were randomized 1:1 to 5 (n = 96) or 10 (n = 90) open label apheresis treatments. The primary endpoint was non-inferiority of clinical activity index score after 12 weeks. RESULTS: The intent-to-treat population comprised 82 and 80 patients for the 5- and 10-treatment groups, respectively. The difference between the two groups in mean clinical activity index was 0.24 with an upper 95% confidence interval of 1.17, which was below a predefined non-inferiority threshold of 1.33. Clinical activity index score improved from baseline in both groups (from 8.7 to 5.6 with 5 treatments, and from 8.8 to 5.4 with 10), with no significant difference between the groups (P = 0.200). Outcomes for the 5- and 10-treatment groups were similar--clinical remission: 44% and 40%, respectively (P = 0.636); clinical response: 56% and 59%, respectively (P = 0.753). The treatment was well tolerated in both groups. CONCLUSIONS: This prospective study comparing apheresis regimens in ulcerative colitis demonstrates that 5 treatments were not inferior to 10 treatments in steroid-refractory or -dependent ulcerative colitis.

OBJECTIVE A comprehensive investigation on the quality of partnership of male patients with erectile dysfunction (ED) after treatment with sildenafil vs. untreated patients, as perceived by both the patients and their female partners. METHODS This report describes an observational, cross-sectional exploratory study comparing ED patients responsive to sildenafil with ED patients prior to therapy. Assessments included the 'International Index of Erectile Function' (IIEF) and the 'Partnerschaftsfragebogen' (PFB), a partnership questionnaire used in German-speaking countries. The comparability of the two study groups was examined using a stepwise logit model. Significant intergroup differences regarding demographics and history were identified and included as confounding variables in the assessment of Quality of Partnership differences using ANCOVA. A regression analysis was performed to determine the association between the mean total IIEF scores and Quality of Partnership measures. RESULTS 105 patients were included in the study. After adjustment for confounding variables, the groups varied significantly with respect to Quality of Partnership as perceived by men (mean score PFB 61.8 +/- 13.9 vs. 54.4 +/- 15.5; p

Summary Dense intranuclear particles, 30 to 40 nm diameter, could be identified in liver specimens from female patients, who immediately after delivery had been inoculated with sera contaminated with non A, non B hepatitis. The same particles were described previously by Kendrey et al. (1975) in a case of acute hepatitis without clinical or serological evidence for hepatitis A and B. The joint occurrence of dense intranuclear particles with typical core particles in cases of chronic B hepatitis show that they are not specific for non A, non B hepatitis. The observed structures are likely to be nonspecific responses of hepatocytic nuclei to different hepatitis viruses. The nature of relationship to the infectious agent remains to be elucidated. Tubular structures in the endoplasmic reticulum and other cytoplasmic inclusions which had been demonstrated in liver cells from chimpanzees inoculated with non A, non B hepatitis, did not occur in our material.

We aimed to understand the risks and benefits of post-inflatable penile prosthesis (IPP) implantation drainage and optimal duration. Our patients were divided into 3 groups: Group 1 (n = 114) had no drain placed, Group 2 had a drain placed for 24 h (n = 114) and Group 3 had a drain placed for 72 h (n = 117). Postoperative scrotal hematoma and prosthesis infection rates were compared between the groups. The patients from Group 3 demonstrated a statistically significant lower incidence of hematoma on the 10th postoperative day: (n = 1, 0.9%) compared to Group 2: (n = 11, 9.6%) and Group 1: (n = 8, 7%), (p = 0.013). However, on the 3rd postoperative day, there was a statistically significant lower incidence of hematoma in both Groups 3 and 2: (0.9% and 6.1%, respectively) vs. Group 1: (11.4%), (p = 0.004). Hematoma rates followed the same group order after the first day of surgery: 1.7% (n = 2), 5.3% (n = 6), and 8.8% (n = 10), respectively, (p = 0.05). Five patients (4.4%) in Group 1 and four patients (3.5%) in Group 2 developed an IPP associated infection, opposed to only a single patient (0.85%) in Group 3, (p = 0.210). We concluded that prolonged scrotal drainage for 72 h after virgin IPP implantation significantly reduces hematoma and infection rates.

Background: Several drugs are approved for the treatment of lower urinary tract symptoms (LUTS) in men, but these are mostly used by clinicians as monotherapies. The combination of different compounds, each of which targets a different aspect of LUTS, seems appealing. However, only few clinical trials have evaluated the effects of combination therapies. Objective: This systematic review analyzes the efficacy and adverse events of combination therapies for male LUTS. Evidence acquisition: PubMed and Cochrane databases were used to identify clinical trials and meta-analyses on male LUTS combination therapy. The search was restricted to studies of level of evidence >= 1b. A total of 49 papers published between January 1988 and March 2012 were identified. Evidence synthesis: The alpha(1)-adrenoceptor antagonist (alpha(1)-blocker)/5 alpha-reductase inhibitor (5-ARI) combination provides the most data. This combination seems to be more efficacious in terms of several outcome variables in patients whose prostate volume is between 30 ml and 40 ml when treatment is maintained for >1 yr; when given for 6 yr. The alpha(1)-blocker/muscarinic receptor antagonist (antimuscarinic) combination was most frequently assessed as an add-on therapy to already existing alpha(1)-blocker therapy. Inconsistent data derive from heterogeneous study populations and different study designs. Currently, the alpha(1)-blocker/antimuscarinic combination appears to be a second-line add-on for patients with insufficient symptom relief after monotherapy. The combination seems to be safe in men with postvoid residual 4 mo concerning safety and efficacy of this combination. The alpha(1)-blocker/phosphodiesterase type 5 inhibitor combination is a new treatment option with only preliminary reports. More studies are needed before definitive conclusions can be drawn. Conclusions: An alpha(1)-blocker/5-ARI combination is beneficial for patients whose prostate volume is between 30 ml and 40 ml when medical treatment is intended for >1 yr. Based on short-term follow-up studies, add-on of antimuscarinics to alpha(1)-blockers is an option when postvoid residual is

Objectives This study evaluated the associated comorbidities and patient satisfaction with treatment options for premature ejaculation (PE), a common sexual dysfunction. Methods A comprehensive, Internet-based survey (the PE Prevalence and Attitudes [PEPA] survey) was conducted among men ages 18–70 in the United States, Germany, and Italy ( n =12,133). Men were classified as having PE based on self-report of low or absent control over ejaculation, resulting in distress for them or their sexual partner or both. Results The prevalence of PE was 22.7% (24.0% in the United States, 20.3% in Germany, and 20.0% in Italy) and did not vary significantly with age among men over age 24 yr. Men with PE were more likely to self-report other sexual dysfunctions (e.g., anorgasmia, low libido, erectile dysfunction) and psychological disturbances (e.g., depression, anxiety, excessive stress) than men without PE ( p 70%) and most likely to have used (>50%) special positions during sex, interrupted stimulation, masturbation, and having intercourse more often than usual to manage their PE. Only 9.0% of men with PE reported having consulted a physician for the condition; 81.9% had to initiate the conversation about PE and 91.5% reported little or no improvement as a result of seeking treatment. Conclusion PE is a highly prevalent sexual problem, with significant sexual and psychological comorbidities. Most men with PE do not seek assistance from their physician, and most of those who do are not satisfied with the results.

Introduction. Vardenafil is a potent and selective phosphodiesterase 5 (PDE5) inhibitor developed for the treatment of erectile dysfunction (ED). Fixed-dose and flexible-dose studies have previously established the efficacy and tolerability of vardenafil. Aim. To assess, besides the usual measures of efficacy, the quality of erection, satisfaction with the sexual experience, symptoms of depression, and overall confidence. Methods. This 12-week double-blind, placebo-controlled flexible-dose study assessed patients from the general ED population. Patients underwent a 4-week treatment-free period before randomization to vardenafil or matching placebo. Initial dosage was vardenafil 10 mg for 4 weeks. At 4 weeks, patients could switch to 5 or 20 mg (or corresponding placebo), or remain on 10 mg for all additional 4 weeks; dose switching was also optional for the last 4 weeks. This paper describes per-patient success in satisfaction with hardness of erection, satisfaction with overall sexual experience, effect on overall self-confidence, and an assessment of symptoms of depression using the Center for Epiderniologic Studies Depression Scale. Results. Mean per-patient satisfaction rates with erection hardness increased after vardenafil treatment to 43%, 59% and 63% at weeks 4, 8, and 12, respectively, compared to placebo with 10%, 21%, and 23% (all P < 0.005 vs. placebo). Vardenafil also improved mean per-patient overall satisfaction 50-65% over the 4-12week study period compared with 17-28% for placebo (P < 0.005). Symptoms of depression were statistically significantly reduced compared to placebo (P = 0.02); the effect was observed particularly in patients who were depressed at baseline (P = 0.01). Significantly more patients in the vardenafil treatment group reported improved self-confidence than those who received placebo (P < 0.005). Conclusions. A flexible-dose regimen of vardenafil improved satisfaction rates, symptoms of depression, and self-confidence, providing patients with an effective ED therapy that contributes to overall improvements in sexual function and confidence.

Despite availability of outcome measures and scales for assessing erectile dysfunction (ED) treatment efficacy, guidelines are not available for assessing broader therapeutic outcomes or defining treatment failure in ED. An International Consensus Advisory Panel was convened to develop guidelines, definitions and a new algorithm for evaluating treatment effectiveness in ED. These new guidelines are recommended for use in both research and clinical practice. A multidisciplinary, international panel, consisting of 11 senior researchers and clinicians, was convened to address pertinent issues concerning therapeutic outcome assessment for ED. The panel utilized a modified Delphi method of consensus development and proposed a new model for outcomes assessment. This model is inherently testable, using existing instruments and current methods of assessment. Following a comprehensive literature review and discussion, the Panel recommended adoption of a new treatment effectiveness conceptual framework or theoretical model for assessing therapeutic outcomes in ED. Treatment effectiveness is presumed to be a combined function of two other factors, treatment response and treatment satisfaction. Treatment response is based on the combined assessment of efficacy and tolerability, and treatment satisfaction on the combined assessment of patient and partner satisfaction. Taken together, these two domains define an overall domain of treatment effectiveness. This therapeutic index would be derived by independently assessing treatment efficacy and satisfaction by means of event logs, questionnaires or the more typical patient interview methods. In conclusion, the Ad Hoc Advisory Consensus Panel recommends adoption of a new framework or conceptual model for conducting ED outcome trials or clinical research. The concept of 'treatment effectiveness' is proposed as a new 'umbrella concept' or distal outcome to be evaluated.

Background. In fixed-dose studies, vardenafil 5, 10, and 20 mg improves erectile function in men with erectile dysfunction (ED). Here, the efficacy and tolerability of vardenafil when used in a flexible-dose regimen was assessed. Methods: In this multicenter trial, 323 patients randomly received vardenafil 10 mg or placebo. After 4 weeks, patients could switch to 5 or 20 mg (or corresponding placebo), or remain on 10 mg for an additional 4 weeks; dose-switching was optional for the last 4 weeks. Efficacy variables included the IIEF-EF domain score, GAQ, and percentage of positive responses to SEP2/SEP3 questions. Results: The IIEF-EF domain score significantly improved from a baseline of moderate ED (12.6-13.1) to mild ED in men on vardenafil (21.0-24.2) compared with placebo (13.7-15.6) at weeks 4, 8, 12, and last observation carried forward (LOCF) (p < 0.005 vs. placebo). A significantly greater proportion of men receiving vardenafil at weeks 4, 8, 12, and LOCF reported improved erections (80-86% vs. 21-36% for placebo, p < 0.005). Successful SEP2 rates increased after vardenafil, reaching 84% at weeks 8 and 12 vs. 49-53% receiving placebo (p < 0.005 vs. placebo). Vardenafil improved successful SEP3 rates ranging from 58% to 74% compared to 22-34% for placebo. The most common adverse events, flushing and headache, were generally mild and transient. Conclusion: In this flexible dose study, vardenafil was well-tolerated, and produced clinically relevant improvements in erectile function in men with ED. (C) 2004 Published by Elsevier B.V.