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Introduction: Clinical research on erectile dysfunction (ED) has focused primarily on the male and the impact of treatment on their erectile function (EF) and sexual quality of life. However, ED affects the quality of life of both the male and the female partner. The literature examining the impact on the female partner resulting from treating the male's ED is somewhat limited., Aims: To determine the efficacy of tadalafil 5 mg taken once daily compared with placebo on men's EF and sexual quality of life, and to determine the impact of this treatment on the female partner's sexual quality of life., Main Outcome Measures: The co-primary outcome measures for this study were changes from baseline to end point in the EF domain of the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) question 2 (SEP-2) and question 3 (SEP-3), and the Sexual Quality of Life (SQoL) domain of the Sexual Life Quality Questionnaire (SLQQ) (subject and partner). Methods. Following a 4-week treatment-free run-in phase, 342 subjects and their partners were randomly assigned to either placebo (N = 78) or tadalafil 5 mg (N = 264) for 12 weeks. The subjects' and partners' responses to study measures were collected throughout the study., Results: Compared with placebo, tadalafil-treated subjects showed a significant improvement on efficacy measures (P < 0.001) including changes in the IIEF-EF, SEP-2 and SEP-3. In addition, the sexual quality of life of men and their female partners, as measured by the SQoL domain, was significantly improved with tadalafil 5 mg taken once daily (P < 0.001) compared with placebo., Conclusions: Tadalafil 5 mg once daily significantly improved EF and sexual quality of life for men with ED. In addition, the sexual quality of life of the female partners of the men treated with tadalafil was significantly improved.

Introduction: With once-daily administration of tadalafil, dosing and sexual activity would no longer need to be temporally linked for patients with erectile dysfunction (ED)., Aim: To evaluate long-term safety and efficacy of tadalafil 5 mg dosed once daily for the treatment of ED., Methods: Patients > or = 18 years of age with ED of any functional severity or etiology received tadalafil 5 mg once daily for 1 (N = 234) or 2 (N = 238) years during the open-label extensions of two previously reported studies. Patients who completed the 1-year open-label extension concluded with a 4-week ED treatment-free period. Baseline was defined as prior to receiving any study drug., Main Outcome Measures: Safety measures included adverse events, electrocardiograms, and clinical laboratory measures. Efficacy measures included the International Index of Erectile Function (IIEF)-Erectile Function (-EF), -Intercourse Satisfaction (-IS), and -Overall Satisfaction (-OS) domain scores, and the Global Assessment Questions (GAQ1: improved erections; GAQ2: improved ability to engage in sexual activity)., Results: Overall, 208/234 (88.9%) and 139/238 (58.4%) patients completed the 1- and 2-year open-label extensions, respectively. No study drug-related serious adverse events were observed. Treatment-emergent adverse events observed in > or = 5% of the patients during the first year of either open-label extension were dyspepsia, headache, back pain, and influenza. No clinically meaningful abnormalities associated with tadalafil were observed for electrocardiograms or clinical laboratory measures. Mean IIEF domain scores improved from baseline to the conclusions of the 1- and 2-year open-label extensions, respectively: -EF, +10.4 and +10.8; -IS, +4.0 and +3.7; and -OS, +3.0 and +3.2. At the conclusion of the 2-year open-label extension, 95.7% and 92.1% of the patients reported positive responses to GAQ1 and GAQ2, respectively., Conclusions: In these long-term, open-label, once-daily dosing studies, tadalafil 5 mg was well tolerated and effective, making it a viable alternative to the current on-demand dosing of tadalafil for men with ED.

Objective: To develop a contemporary, evidence-based definition of premature ejaculation (PE)., Methods: There are several definitions of PE; the most commonly quoted, the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders - 4th Edition - Text Revision, and other definitions of PE, are all authority-based rather than evidence-based, and have no support from controlled clinical and/or epidemiological studies. Thus in August 2007, the International Society for Sexual Medicine (ISSM) appointed several international experts in PE to an Ad Hoc Committee for the Definition of PE. The committee met in Amsterdam in October 2007 to evaluate the strengths and weaknesses of current definitions of PE, to critically assess the evidence in support of the constructs of ejaculatory latency, ejaculatory control, sexual satisfaction and personal/interpersonal distress, and to propose a new evidence-based definition of PE., Results: The Committee unanimously agreed that the constructs which are necessary to define PE are rapidity of ejaculation, perceived self-efficacy, and control and negative personal consequences from PE. The Committee proposed that lifelong PE be defined as a male sexual dysfunction characterized by ejaculation which always or nearly always occurs before or within about one minute of vaginal penetration, and the inability to delay ejaculation on all or nearly all vaginal penetrations, and negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy. This definition is limited to men with lifelong PE who engage in vaginal intercourse. The panel concluded that there are insufficient published objective data to propose an evidence-based definition of acquired PE., Conclusion: The ISSM definition of lifelong PE represents the first evidence-based definition of PE. This definition will hopefully lead to the development of new tools and patient-reported outcome measures for diagnosing and assessing the efficacy of treatment interventions, and encourage ongoing research into the true prevalence of this disorder, and the efficacy of new pharmacological and psychological treatments.

Alpha-blockers, the current common treatment for lower urinary tract symptoms (LUTS), are also used to treat bladder outlet obstruction (BOO), but the effect is not as clinically significant as in LUTS. All currently marketed phosphodiesterase type 5 (PDE5) inhibitors have recently been shown to significantly affect LUTS, although BOO-related efficacy has not been determined. Therefore, the extent of a causal relationship between LUTS and underlying benign prostatic enlargement (BPE) is questionable. LUTS may also be interpreted as symptoms related to detrusor overactivity, especially when no significant BOO is associated with BPE. Research is required to understand the efficacy of PDE5 inhibitors in LUTS but not in BOO. For vardenafil, nonclinical experiments and initial, preliminary clinical data suggest that the underlying effect may occur on the detrusor and not the prostate.

Background: Phosphodiesterase (type) 5 (PDE5) inhibitors are currently administered on demand for treatment of erectile dysfunction (ED). Once-daily dosing has been suggested to benefit patients., Objective: To determine whether daily vardenafil use provides added clinical benefits to patients compared with on-demand dosing., Design, Setting, and Participants: In this placebo-controlled, double-blind, multicentre parallel-group study, men with mild-to-moderate ED were randomised to 24 wk of treatment, followed by a 4-wk washout., Intervention: Patients were randomised to receive once-daily vardenafil 10mg plus on-demand placebo for 12 or 24 wk, or once-daily placebo plus on-demand vardenafil 10mg for 24 wk., Measurements: Primary efficacy variable was the between-group difference in change in International Index of Erectile Function-Erectile Function domain (IIEF-EF) score from baseline to end of washout. Secondary variables included change from baseline in proportion of positive respondents to Sexual Encounter Profile questions and in satisfaction with treatment as assessed with the Treatment Satisfaction Scale (TSS)., Results and Limitations: LS mean changes from baseline in IIEF-EF scores were 2.02, 2.29, and 2.63 for vardenafil 12 wk once daily, 24 wk once daily, and 24 wk on demand, respectively. After washout, the trend was towards improved IIEF-EF scores in the on-demand group (20.58 [+/-0.96]) versus both once-daily groups (12 wk, 19.88 [+/-0.93]; 24 wk, 20.11 [+/-0.94]). Furthermore, there were no significant between-group differences in the percentage of patients with "normal" erectile function. TSS analyses demonstrated no significant differences between treatment groups. This study recruited patients with mild-to-moderate ED; therefore, the results may not be the same as in patients with severe ED., Conclusions: Once-daily vardenafil did not produce greater sustained effects on EF than on-demand vardenafil in men with mild-to-moderate ED, suggesting that daily dosing of PDE5 inhibitors does not produce sustained clinical benefits beyond cessation of treatment above those observed with on-demand administration.

Introduction: The medical literature contains several definitions of premature ejaculation (PE). The most commonly quoted definition, the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision, and other definitions of PE are all authority based rather than evidence based, and have no support from controlled clinical and/or epidemiological studies., Aim: The aim of this article is to develop a contemporary, evidence-based definition of PE., Methods: In August 2007, the International Society for Sexual Medicine (ISSM) appointed several international experts in PE to an Ad Hoc Committee for the Definition of Premature Ejaculation. The committee met in Amsterdam in October 2007 to evaluate the strengths and weaknesses of current definitions of PE, to critique the evidence in support of the constructs of ejaculatory latency, ejaculatory control, sexual satisfaction, and personal/interpersonal distress, and to propose a new evidence-based definition of PE., Results: The committee unanimously agreed that the constructs that are necessary to define PE are rapidity of ejaculation, perceived self-efficacy and control, and negative personal consequences from PE. The committee proposed that lifelong PE be defined as ". . . a male sexual dysfunction characterized by ejaculation which always or nearly always occurs prior to or within about one minute of vaginal penetration, and the inability to delay ejaculation on all or nearly all vaginal penetrations, and negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy." This definition is limited to men with lifelong PE who engage in vaginal intercourse. The panel concluded that there are insufficient published objective data to propose an evidence-based definition of acquired PE., Conclusion: The ISSM definition of lifelong PE represents the first evidence-based definition of PE. This definition will hopefully lead to the development of new tools and Patient Reported Outcome measures for diagnosing and assessing the efficacy of treatment interventions and encourage ongoing research into the true prevalence of this disorder and the efficacy of new pharmacological and psychological treatments.

Introduction: Benign prostatic hyperplasia (BPH) is associated with bothersome lower urinary tract symptoms (LUTS) and reduced patient quality of life (QoL). Phosphodiesterase (type) 5 (PDE5) inhibitors such as vardenafil are commonly used for the treatment of erectile dysfunction (ED), but have also been shown to improve the symptoms of BPH. This randomised, double-blind, placebo-controlled study investigated the effects of vardenafil on LUTS and QoL in men with BPH/LUTS, with or without concomitant ED., Methods: Men aged 45-64 yr with BPH/LUTS and an International Prostate Symptom Score (IPSS) > or =12 were randomised to receive either 10mg vardenafil or placebo twice daily. LUTS were assessed with the use of two primary efficacy parameters, IPSS score and maximum urinary flow rate (Qmax), as well as postvoid residual (PVR) urine volume; ED was measured with the use of the erectile function (EF) domain score of the International Index of Erectile Function (IIEF-EF); and QoL was assessed with the Urolifetrade mark QoL-9 questionnaire., Results: After 8 wk of treatment, there was a significant improvement in the IPSS total score in the vardenafil group compared with placebo (-5.9 and -3.6, respectively; p=0.0013). Nominally significant improvements in irritative and obstructive IPSS subscores (p=0.0017 and p=0.0081, respectively), EF (p=0.0001), and Urolife QoL-9 (p<0.0001) were also associated with vardenafil treatment. Qmax and PVR urine volume did not change significantly with treatment, although baseline values were already considered close to normal. Vardenafil was generally well tolerated, with most adverse events considered mild or moderate in severity., Conclusions: Vardenafil treatment significantly improved LUTS, EF, and QoL in men with BPH/LUTS. Vardenafil may be considered a promising treatment option for men with symptoms secondary to BPH.

Objectives: To characterize premature ejaculation (PE) in five European countries using intravaginal ejaculatory latency time (IELT) and the Premature Ejaculation Profile (PEP)., Methods: This 8-wk, multicenter, observational study enrolled men >or=18 yr of age and their female partners. Clinicians diagnosed PE using the DSM-IV-TR criteria and at least moderate, subject-reported, ejaculation-related personal distress or interpersonal difficulty. The PEP was administered at baseline and weeks 4 and 8. Partners measured IELT; the average stopwatch-measured IELT for each 4-wk period was calculated and compared with the man's screening-estimated IELT. Relationships between individual PEP measures and IELT were assessed with path analysis., Results: PE was diagnosed in 201 of 1115 men. Findings were similar to those in a similarly conducted US study. Mean IELT was lower in the PE versus the non-PE group (3.3 vs. 10.0min, respectively), but substantial overlap was observed. Men with PE and their partners reported significantly worse control over ejaculation, ejaculation-related personal distress, satisfaction with sexual intercourse, and ejaculation-related interpersonal difficulty than men without PE and their partners. Path analysis showed that perceived control over ejaculation had a significant effect on ejaculation-related personal distress and satisfaction with sexual intercourse; IELT had an effect on control over ejaculation, no direct effect on satisfaction with sexual intercourse, and a small direct effect on ejaculation-related personal distress., Conclusions: No major cultural differences existed between EU and US men with and without PE and their female partners. These results emphasize the importance of the PEP measures, especially perceived control over ejaculation, in characterizing PE.

Aim: To assess the incidence of serious cardiovascular disease (CVD) events [i.e. myocardial infarction (MI) and stroke] and all-cause mortality in men with erectile dysfunction (ED) who received prescriptions for sildenafil., Methods: The International Men's Health Study (IMHS) was a prospective, observational cohort study of patients with ED and a new or existing prescription for sildenafil. Baseline and follow-up questionnaires provided information on demographics, CVD risk factors and ED. Postevent questionnaires were mailed to patients following possible nonfatal CVD events to collect information related to exposure to sildenafil/ED treatments before the event., Results: Thirty-five CVD events were reported in 30 patients in the analysis set (n = 3813). The incidence of all-cause mortality, MI and stroke was 0.4, 0.6 and 0.1 per 100 patient-years of observation respectively. Among the six men who reported using sildenafil in the month before a nonfatal CVD event, two reported use in the 24 h before the event., Conclusion: The results of the IMHS support previous reports that ED and CVD are often comorbid and share risk factors.

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<0.05 for all). Men with PE were most aware of (>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: There are no psychometrically validated assessment tools designed to solely and specifically evaluate satisfaction with the quality of erections., Aim: To develop and psychometrically analyze the Quality of Erection Questionnaire (QEQ), a new patient-reported measure developed to evaluate men's satisfaction with the quality of their erections., Methods: The questionnaire was developed through in-depth qualitative interviews of men with erectile dysfunction (ED) in the United States and Australia. An exploratory methodology study was conducted on 65 men with ED. Subsequently, the psychometric properties were confirmed in a larger dataset of 558 men with ED from two combined clinical trials., Main Outcome Measures: Identification of potential redundancy or outliers in items (Pearson inter-item correlations); exploratory factor analysis (unrotated and varimax rotated); internal consistency (Cronbach's alpha); convergent validity (Pearson correlation coefficients between the QEQ total score and domain scores of the International Index of Erectile Function); known-groups validity (ability of the QEQ scores to differentiate between ED severity groups); test-retest reliability (Pearson correlation coefficient)., Results: The QEQ demonstrated excellent convergent and known-groups validity. Additional analysis demonstrated high internal consistency (Cronbach's alpha, 0.92). Item analysis demonstrated a unidimensional structure and suggested that satisfaction with hardness may be the key driver for satisfaction with overall quality of erections (r = 0.8). The smaller exploratory study demonstrated good test-retest reliability (r = 0.82)., Conclusions: The QEQ is a six-item, patient-reported measure with a unidimensional structure, which produces a total score that may be transformed to a 0-100 scale. Psychometric analysis confirmed reliability and validity of the QEQ, which solely and specifically evaluates satisfaction of men with the quality of their erections. The QEQ is a potentially useful measure for monitoring and evaluating treatment in those who are bothered by, or concerned about, their erectile function.

Objective: Sildenafil and apomorphine are oral agents for the improvement of erection hardness. The aim of the study was a direct comparison of the two compounds under clinical routine conditions., Methods: 131 previously untreated men with erectile dysfunction (ED) were enrolled in a cross-over trial and randomly allocated to 50 mg sildenafil or 2 mg apomorphine. Dose-adaptation was allowed as required., Results: Improvements in rigidity, the capacity to get and maintain an erection, and sexual confidence were statistically significantly larger with sildenafil (p <0.0001). 90% of the men were satisfied with sildenafil as compared to 46% with apomorphine. At study end, 95% of the patients preferred sildenafil. Both agents were well tolerated., Conclusions: In this cross-over comparison under clinical routine conditions men reported superior efficacy of sildenafil vs apomorphine together with a statistically significantly higher treatment satisfaction.

Introduction: Data from head-to-head clinical trials of phosphodiesterase type 5 (PDE5) inhibitors are scarce, making it difficult for clinicians to differentiate among these agents to select the most appropriate treatment for their patients with erectile dysfunction (ED)., Aim: This randomized, double-blind, crossover head-to-head clinical trial compared patient preference, efficacy, and safety of vardenafil and sildenafil in men with ED and diabetes, hypertension, and/or hyperlipidemia., Methods: Prospective analysis was performed on two studies in which 1,057 men were randomized to vardenafil 20 mg (N = 530) or sildenafil 100 mg (2 x 50 mg encapsulated tablets) (N = 527) for 4 weeks. Following a 1-week washout, patients switched treatment for 4 weeks., Main Outcome Measures: Patients were asked about overall preference: "Overall, which medication do you prefer?", plus 11 other preference questions relating to their ED treatment. Efficacy assessments after each treatment period included the erectile function (EF) domain score of the International Index of Erectile Function (IIEF); Sexual Encounter Profile (SEP) diary questions SEP2 and SEP3; Global Assessment Question (GAQ); and Treatment Satisfaction Scale (TSS). Data regarding adverse events were collected throughout the study., Results: A total of 931 men (mean age 57.9 years) were included in the intent-to-treat (ITT) population. Non-inferiority of vardenafil over sildenafil was achieved for overall preference (vardenafil 38.9%; sildenafil 34.5%; and no preference 26.6%). Additionally, the change from baseline in the EF domain score of the IIEF achieved nominal significance for vardenafil over sildenafil (10.00 vs. 9.40; P = 0.0052). Patients also had a higher percentage of positive responses for vardenafil for SEP2, SEP3, GAQ, and 12 of 19 questions on the TSS. Both drugs were well tolerated., Conclusions: This randomized, double-blind, head-to-head trial in ED patients with cardiovascular risk factors demonstrated noninferiority of vardenafil for overall preference. Vardenafil achieved nominal statistical superiority over sildenafil for several frequently used efficacy measures. Both drugs were well tolerated.

Objectives: This study explored the efficacy of vardenafil in men with erectile dysfunction (ED) when taken 8 hours before sexual intercourse., Methods: A 10-week, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study of vardenafil (5, 10 or 20mg) was conducted in men with ED for >6 months who failed >or=50% of intercourse attempts during a 4-week treatment-free run-in period. Sexual Encounter Profile Question 3 (SEP3) was the primary efficacy measure; secondary measures included SEP2, International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, Global Assessment Question (GAQ), Global Confidence Question (GCQ) and Erection Quality Scale (EQS). Adverse-event and safety monitoring were conducted throughout., Results: 383 patients were randomized to vardenafil (n=194) or placebo (n=189). Patients treated with vardenafil 8 hours before sexual activity achieved clinically meaningful (>or=18%) and statistically significantly greater least-squares mean per-patient SEP3 and SEP2 success rates over weeks 2-10, compared with patients receiving placebo (SEP3 69% vs 34%; SEP2 81% vs 51%; both p<0.001). SEP3 and SEP2 measures demonstrated the significant superiority of vardenafil over placebo from week 2 onwards (p<0.001). Measurements of IIEF-EF domain score, GAQ, GCQ and EQS showed that vardenafil led to significantly greater improvements in erectile function, compared with placebo (all p<0.001). Vardenafil was generally well tolerated., Conclusions: The extended duration of efficacy of vardenafil up to 8 hours postdose may provide couples with more flexibility in their sexual life than anticipated.

Background: Erectile dysfunction (ED) is a chronic disease; however, therapy is currently administered as needed with oral phosphodiesterase 5 (PDE5) inhibitors like tadalafil. Because the 17.5-h half-life of tadalafil enables therapeutic plasma levels to be sustained with daily administration, tadalafil is a good candidate for once daily dosing therapy., Methods: This multicenter, randomized, double-blind, placebo-controlled, parallel-group, 12-week study enrolled 268 men 1:2:2 to placebo, tadalafil 5mg, and tadalafil 10mg taken once daily. Primary efficacy measures included changes in the International Index of Erectile Function Erectile Function domain (IIEF EF), Sexual Encounter Profile diary Questions 2 (SEP2: successful penetration), and 3 (SEP3: successful completion of intercourse), and tolerability. Secondary measures included percentage of patients at endpoint who reported improved erectile function (EF), and percentage who reported "no ED" (IIEF EF score 26-30)., Results: For patients who took placebo, tadalafil 5mg, and tadalafil 10mg, changes from baseline to endpoint were, respectively, 0.9, 9.7, and 9.4 for IIEF EF; 11.2, 36.5, and 39.4 for SEP2; and 13.2, 45.5, and 50.1 for SEP3. At endpoint, 28.3%, 84.5%, and 84.6% reported improved erections, and 8.3%, 51.5%, and 50.5% reported "no ED," respectively. All comparisons between tadalafil and placebo were significant (p<0.001). Adverse events that occurred in at least 5% of patients were dyspepsia, headache, back pain, upper abdominal pain, and myalgia; nine patients (3.4%) discontinued because of adverse events., Conclusions: Once-a-day tadalafil 5mg or 10mg was well tolerated and significantly improved EF in men with ED.

Background/aims: The natural course of the hepatitis C virus genotype 1b (HCV-1b) infection is still unclear but important for therapeutic decisions. There are few unbiased long-term follow-up studies with known dates of infection., Methods: Between August 1978 and March 1979, 14 HCV-1b contaminated batches of anti-D immunoglobulin had been administered to 2867 women for prophylaxis of rhesus isoimmunization throughout East Germany. We reexamined 1980 women, representing 70% of the total cohort of 15 centers., Results: After application of the contaminated anti-D, 93% of the recipients developed an acute hepatitis C. After 25 years, 86% of the 1833 affected women still tested positive for hepatitis C virus antibodies and 46% for HCV RNA. Only nine (0.5%) had overt liver cirrhosis, 30 women (1.5%) developed pre-cirrhotic stages and one HCC was diagnosed. Ten (0.5%) died of HCV related complications, half of these related to additional comorbidity. In the last 5 years, a continuous, but low increase of fibrotic scores was observed., Conclusions: Young women without comorbidity may clear HCV (1b) infection in more than half of the cases, or develop mild chronic hepatitis C. We confirmed the low risk of progression to cirrhosis in this cohort within 25 years.

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 (Pc.001). Vardenafil was generally well tolerated; most adverse events were mild to moderate, with headache and flushing reported most frequently., Conclusion: During this 12-week study, vardenafil produced consistently higher reliability of penetration and maintenance of erection rates compared to placebo and was generally well tolerated in patients with erectile dysfunction.

Metabolic diseases are common diseases in the Western world. Many of these diseases, including diabetes mellitus, hyperlipoproteinemia, gout, calcinosis, and hemochromatosis, are associated with skin diseases or often present with specific cutaneous signs. A knowledge of cutaneous manifestations helps to identify patients at risk, establish the internal diagnosis, and monitor the adverse effects of therapy.

Background: Advanced liver cirrhosis is characterized by cardiovascular changes, such as low arterial blood pressure, peripheral vasodilation and renal vasoconstriction. As a consequence, renal hypoperfusion, impaired diuresis and natriuresis and eventual hepatorenal syndrome may ensue. Previous studies using head-out water immersion to increase central blood volume have demonstrated the functional nature of the renal abnormalities. Enhanced external counterpulsation (EECP) is a new non-invasive cardiac assist device to augment diastolic blood pressure by electrocardiogram-triggered diastolic inflation and deflation of cuffs wrapped around the lower extremities. We investigated whether EECP would improve renal dysfunction of liver cirrhosis., Methods: Twelve healthy controls and 19 patients with liver cirrhosis were observed during 2 h of baseline followed by 2 h of EECP. The following parameters of renal and cardiovascular function were measured: renal plasma flow by para-aminohippurate clearance, glomerular filtration rate (GFR) by inulin clearance, urine flow rate, urinary excretion rates of sodium and chloride, mean arterial blood pressure (MAP), renal vascular resistance (RVR) and plasma concentrations of renin, atrial natriuretic peptide (ANP), endothelin-1, antidiuretic hormone, epinephrine and N-epinephrine., Results: EECP was well tolerated by healthy controls and cirrhotic patients alike. EECP increased MAP (cirrhotic patients: from 74+/-18 to 88+/-20 mmHg, P<0.01; controls: from 89+/-8 to 94+/-5 mmHg, P = NS) and ANP (cirrhotic patients: from 23+/-18 to 30+/-20 ng/l, P<0.05; controls: from 11+/-4 to 16+/-5 ng/l, P<0.01). The plasma renin concentration decreased (cirrhotic patients: from 98+/-98 to 58+/-57 ng/l, P<0.01; controls: from 4.6+/-1.6 to 3.4+/-1.1 ng/l, P<0.01). This was associated with improvement of the urinary flow rate (cirrhotic patients: from 3.6+/-1.8 to 4.6+/-0.7 ml/min, P<0.05; controls: from 1.8+/-1.5 to 2.8+/-1.9 ml/min, P<0.05), as well as of the sodium and chloride excretion rates in both groups. However, in contrast to healthy controls, GFR and renal plasma flow in cirrhotic patients failed to rise significantly. Renal vascular resistance fell numerically in healthy controls (68+/-5 vs 55+/-4 mmHg . min/l; P = NS). In contrast, RVR showed a significant increase by approximately 20% in cirrhosis (67+/-4 vs 80+/-8 mmHg . min/l; P<0.05). Endothelin-1 levels fell in controls (0.38+/-0.42 vs 0.31+/-0.35; P<0.05), whereas they remained statistically unchanged in cirrhotic patients. Epinephrine, N-epinephrine and vasopressin were not altered by EECP in either group., Conclusions: EECP is an effective procedure to augment renal excretory function in healthy volunteers as well as in patients with cirrhosis. In healthy volunteers, GFR and renal plasma flow increased during EECP. In contrast, these parameters remained unchanged in the patients and their renal vascular resistance increased during EECP. Therefore, EECP improves diuresis, but does not influence the vasoconstrictive dysregulation of the kidneys in liver cirrhosis.

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 an 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 Epidemiologic 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 4-12 week 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.

Leptin and adiponectin are proteins produced and secreted from white adipose tissue and are important regulators of energy balance and insulin sensitivity. Seasonal changes in leptin and adiponectin have not been investigated in mammalian hibernators in relationship to changes in fat cell and fat mass. We sought to determine the relationship between serum leptin and adiponectin levels with seasonal changes in lipid mass. We collected serum and tissue samples from marmots (Marmota flaviventris) in different seasons while measuring changes in fat mass, including fat-cell size. We found that leptin is positively associated with increasing fat mass and fat-cell size, while adiponectin is negatively associated with increasing lipid mass. These findings are consistent with the putative roles of these adipokines: leptin increases with fat mass and is involved in enhancing lipid oxidation while adiponectin appears to be higher in summer when hepatic insulin sensitivity should be maintained since the animals are eating. Our data suggest that during autumn/winter animals have switched from a lipogenic condition to a lipolytic state, which may include leptin resistance.

Introduction: Advances in understanding of the biochemistry and physiology of penile erection have led to breakthroughs in pharmacotherapy of erectile dysfunction., Aim: To provide recommendations/guidelines concerning state-of-the-art knowledge for the putative molecular and cellular mechanisms of action of centrally and peripherally acting drugs currently utilized in pharmacotherapy of erectile dysfunction., Methods: An international consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a process over a two-year period. Concerning the Pharmacotherapy for Erectile Dysfunction Committee there were 25 experts from 10 countries., Main Outcome Measure: Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate., Results: Selective and potent oral PDE5 inhibitors have significantly more affinity than cGMP and form broader molecular interactions with multiple amino acids, thereby blocking access to cGMP in the catalytic sites of the PDE5 enzyme. PDE5 inhibitors, which vary as to biochemical potency, selectivity and pharmacokinetics, lead to cGMP elevation and relaxation facilitation of penile corpus cavernosum smooth muscle cells following sexual stimulation. Various centrally acting drugs influence sexual behaviour. In particular, the dopaminergic substance apomorphine is a central enhancer that acts in the paraventricular nucleus of the hypothalamus as a dopamine (D2) receptor agonist, induces and increases penile erection responses via disinhibition, following sexual stimulation., Conclusions: There is a need for more research in the pharmacotherapeutic development of central and peripheral agents for safe and effective erectile dysfunction treatment.

We report on three women with phenprocoumon-induced liver failure. In all three, jaundice was the main symptom. Liver failure was manifest 6 months after initial exposure to phenprocoumon in two women and 18 months in the third. None received corticosteroids. The course was prolonged in each patient, but all three finally recovered. Liver failure associated with oral anticoagulation is rare. Most published reports describe only individual cases. Instances of fatal outcome and instances requiring liver transplantation for survival have been seen. Coumarin treatment should be considered as a possible etiology of acute liver failure, even if the drug has been administered for a longer period without any previous problems. While cross-reactions with other coumarin substances have been reported, if coumarin anticoagulation is absolutely required, use of a congener under close monitoring seems justifiable.

Introduction: Vardenafil, a potent and selective oral PDE5 inhibitor, is efficacious and generally well-tolerated in men with erectile dysfunction (ED). Of considerable interest to patients and physicians is an understanding of the time required after dosing to attain penile erection sufficient for successful sexual intercourse., Aim: To determine the earliest time to onset of action of vardenafil 10 and 20 mg leading to successful intercourse compared to placebo in men with ED., Methods: A prospective, randomized, double-blind, parallel-group, at-home study of 732 men with ED (mean age 55.5 years) was conducted at 64 sites in North America and Europe. Following a 4-week run-in period, patients were randomized to either vardenafil 10 (N = 237) or 20 mg (N = 248) or placebo (N = 247) to be taken on demand over 4 weeks. Using a stopwatch, patients recorded the elapsed time from dosing to attainment of an erection perceived to be adequate for penetration that led to intercourse completion. Earliest time of onset was defined as the fastest time among the first four doses for each patient. Time points from 25 to 5 minutes were tested for significance (alpha = 0.025) using a backward stepping procedure., Results: Mean baseline erectile function domain score (13.4) indicated moderate ED. Within 25 minutes after dosing, 50%/53% of men on vardenafil 10/20 mg had at least one erection in the first four doses perceived to be sufficient for penetration with subsequent intercourse completion compared to 26% on placebo (P < 0.0001). A statistically superior response to vardenafil vs. placebo was observed in these responders at all times >or= 10 and >or= 11 minutes (P < 0.025) in the 10 and 20 mg groups, respectively. In a retrospective analysis using time intervals of

Erectile dysfunction (ED) tends to be associated with other diseases, the common basis of which is endothelial dysfunction. ED is also frequently combined with LUTS and the common basis for both conditions seems to be elevation of Rho-kinase activity and decrease of NO concentration. Because all three PDE 5 inhibitors sildenafil, tadalafil, and vardenafil have a common mode of action, i.e., inhibition of PDE 5, they are not different in terms of their efficacy and safety profile except for color vision disturbances which are more common after sildenafil and back pain/myalgia more often observed after tadalafil. The main differentiating characteristics among the three PDE 5 inhibitors are their pharmacokinetics. These are ultimately responsible for the observation that in head-to-head comparative trials depending on the respective study design the overwhelming majority of the patients opted either for tadalafil as the longest acting PDE 5 inhibitor (36 h) or for vardenafil as a relatively rapidly acting drug. All published studies so far have shown that in terms of the cardiovascular risk profile (myocardial infarction rate) all three PDE 5 inhibitors performed better than placebo although the results were not statistically significant. Without any exception it applies to all three PDE 5 inhibitors that they are absolutely contraindicated in patients taking nitrate- or molsidomine-containing medications and that they may interact in particular with non-uroselective alpha-adrenoceptor blockers. This is why their simultaneous application with PDE 5 inhibitors has to be avoided.In the near future chronic (daily) application of a PDE 5 inhibitor may show advantages, at least in those 50-60% of all patients in whom there is a high likelihood of endothelial dysfunction due to the diagnostic (penile duplex Doppler) outcome. Possible new developments in the management of ED with a time frame of 5-8 years until their market approval are guanylate cyclase activators, Rho-kinase inhibitors, melanocortin receptor agonists, gene therapy, and tissue engineering.

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 20mg 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 10mg or placebo. After 4 weeks, patients could switch to 5 or 20mg (or corresponding placebo), or remain on 10mg 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.

This randomised, double-blind study assessed the long-term efficacy and tolerability of vardenafil 10 and 20 mg in men with erectile dysfunction (ED). A total of 566 men who completed an initial 12-month treatment period entered a 12-month extension. In these men, both doses of vardenafil produced improvement in scores for the 'erectile function' Domain of the International Index of Erectile Function, evident from week 4 and maintained through 2 years. Sexual Encounter Profile diary responses indicated that following treatment, penetration was achieved on 92-94% of attempts and erections that lasted long enough for successful intercourse were achieved on 87-89% of attempts. In response to the General Assessment Question, 90-92% of patients reported improved erections with vardenafil. Most treatment-emergent events were mild and transient with no cardiovascular safety concerns. These results support the long-term efficacy, reliability and tolerability of vardenafil 10 and 20 mg in men with ED.

Erectile dysfunction (ED) management in the following 3-5 years will be dominated by substances targeting the L-arginine-NO-guanylate cyclase-cGMP-PDE-5 pathway, resulting in an intracellular elevation of the cGMP concentrations. Promising alternatives to the PDE-5 inhibitors, such as guanylate cyclase activators and Rho-kinase inhibitors, may also effectively compliment a PDE-5 inhibitor. Intranasal application of the melanocortin agonist PT 141 (Melanotan II) seems to be promising. As scheduled sexual activities are not preferred by the majority of couples, the future of ED-therapy will focus on drugs with a 1-2 day long efficacy window, or a daily bedtime application of low dosage agents which result in nocturnal reoxygenation of the cavernous bodies and in turn in functional improvement. Elevation of the cGMP levels and improvement of endothelial function as a result of this approach also promises benefits in cardiovascular diseases and in LUTS.

Objectives: To assess whether vardenafil would improve erectile function irrespective of etiology, baseline severity, or patient age. The consistency of the response over time was also evaluated., Methods: A multicenter, randomized, double-blind, placebo-controlled at-home study of vardenafil treatment (5, 10, and 20 mg) was performed. This secondary analysis compared the mean International Index of Erectile Function (IIEF) erectile function domain scores of various subgroups at 12 weeks of treatment. These populations included organic, psychogenic, or mixed etiologies; mild, moderate, or severe baseline severity; and four age groups (younger than 45, 45 to 55, 56 to 65, and older than 65 years). In addition, all IIEF domains were compared at sequential 4-week periods, before and during treatment., Results: In the 580 men of the intent-to-treat population, the mean erectile function domain scores were statistically greater than placebo, irrespective of etiology, baseline severity, or age. This was seen at all dosages. Compared with placebo, vardenafil statistically improved the IIEF domain scores of erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction after 4 weeks of treatment, and these improvements were maintained for 12 weeks. The rates of the most common adverse events (headache, flushing, and dyspepsia) were either constant or declined over time; they were generally mild to moderate and transient in nature., Conclusions: Vardenafil improved erectile function regardless of the general etiology, baseline severity of erectile dysfunction, or patient age. Improvements in erectile function and other key IIEF domains were consistently seen throughout the study.

Objectives: To examine a potential association between the response to the phosphodiesterase-5 inhibitor sildenafil and angiotensin-converting enzyme (ACE), as well as NOS3 G894T genotypes in patients with erectile dysfunction (ED). An insertion/deletion (I/D) polymorphism in the gene encoding the ACE and a single nucleotide exchange polymorphism (G894T) in the gene NOS3 encoding endothelial nitric oxide synthase have been associated with cardiovascular disorders., Methods: The response to sildenafil in 113 men with ED was monitored according to the patients' diaries. ACE and NOS3 genotypes were determined in patients with ED and in 108 healthy male blood donors., Results: Genotype distributions of ACE and NOS3 polymorphisms in the patient group were similar to those of the healthy control group. Analysis of the response to sildenafil revealed that 15 of 20 individuals homozygous for the ACE II genotype showed a positive erectile response after sildenafil use and only 46 of 93 D allele (combined DD and DI genotypes) carriers had a positive response (positive erectile response, odds ratio 3.07, 95% confidence interval 1.03 to 9.13, P = 0.04; chi-square test). Analysis of NOS3 genotypes revealed that 30 of 52 individuals homozygous for the G894 allele had a sufficient response to sildenafil and only 4 of 12 patients homozygous for the 894T allele had a sufficient erection., Conclusions: It appears that patients with elevated ACE serum concentrations, as associated with the D allele of the ACE I/D polymorphism, are less likely to respond to sildenafil.

Objectives: To examine the therapeutic effects of tadalafil on erectile dysfunction (ED) at 24 and 36 hours after dosing., Methods: A multicenter, randomized, double-blind, placebo-controlled, parallel-group study of 348 men (mean age 57 years) with ED was conducted in Europe and the United States. Patients were stratified by baseline severity of ED using the Erectile Function domain score of the International Index of Erectile Function and then randomly allocated within the severity group to receive tadalafil 20 mg (n = 175) or placebo (n = 173). Subsequently, participants were randomly assigned to two 4-week treatment intervals, during which they were requested to attempt sexual intercourse approximately 24 or 36 hours after tadalafil or placebo dosing. The primary outcome measure was the proportion of successful sexual intercourse attempts (completed to ejaculation) according to patient self-report using the Sexual Encounter Profile diary., Results: Of the 348 patients, 327 (94%) completed the trial (163 of 175 in the tadalafil group and 164 of 173 in the placebo group). Thirty-six hours after tadalafil dosing, 59.2% of intercourse attempts were successful versus 28.3% in the placebo group (P <0.001). The proportion of successful intercourse attempts at approximately 24 hours after treatment was also significantly greater with tadalafil (52.9%) than with placebo (29.1%; P <0.001). Tadalafil was well tolerated. The incidences of four treatment-emergent adverse events were significantly greater in the tadalafil group than in the placebo group (all P <0.05): headache, flushing, dyspepsia, and myalgia., Conclusions: Tadalafil 20 mg is an effective and well-tolerated treatment for ED that has a period of responsiveness of up to 36 hours.

Purpose: Sildenafil is the oral phosphodiesterase-5 inhibitor that revolutionized treatment for erectile dysfunction. We investigated a potential association of the G protein beta 3 subunit (GNB3) C825T polymorphism, a determinant of intracellular signal transduction, with the drug response to sildenafil in patients with erectile dysfunction., Materials and Methods: In 113 men with erectile dysfunction and 111 healthy male controls genotype status of the GNB3 C825T polymorphism was determined by polymerase chain reaction and restriction analysis. Patients with erectile dysfunction received sildenafil at a dose of 25 to 100 mg. according to the individual erectile response. Drug response was measured by interviewing the patient according to the erection scale of 0 to 5., Results: The GNB3 genotype distribution of patients with erectile dysfunction exactly matched that of healthy controls. Analysis of the response to sildenafil revealed a significant association of C825T allele status with the erectile response to sildenafil. In the group with TT genotype we observed a 90.9% response but only a 50.9% and 48.9% response in patients with the CC and TC genotype, respectively. The odds ratio for a positive erectile response was 10.0 (95% CI 1.2 to 81.1) for patients with the TT versus the TC/CC genotype (p = 0.01)., Conclusions: The response to sildenafil is significantly associated with GNB3 C825T genotype status in patients with erectile dysfunction.

IC351 (tadalafil, trade name Cialis) is a new representative compound of the second generation of selective phosphodiesterase 5 (PDE-5) inhibitors. The selectivity ratio vs PDE-5 is more than 10 000 for PDE-1 through PDE-4 and PDE-7 through PDE-10 and 780 for PDE-6. In the European daily-dosing trial, the efficacy rates were up to 93% for successful intercourses with completion in the 50-mg dose in patients with mild to moderate erectile dysfunction (ED). In two different dose-ranging studies with 2-25 mg taken as needed, efficacy rates of up to 88% improvement in erections and up to 73% successful intercourses with completion were achieved. In a placebo-controlled, fixed-dose (10- and 20-mg) trial in diabetic patients, improved erections of 56% and 64% were reported compared with 25% after placebo. Drug-related adverse effects, with headache in up to 23% of patients (placebo, up to 17%), dyspepsia in up to 11% (placebo, up to 7%), back pain in up to 4.7% (placebo, 0%), and myalgia in up to 4.1% (placebo, up to 2.4%), were mostly mild to moderate. Neither drug-related serious cardiovascular adverse events nor color vision disturbances were encountered. The long half-life (>17 h), with a comfortably long window of opportunity, releases couples from the need to plan sexual activities and therefore provides the highest amount of spontaneity for sexual activities.

Vardenafil, a novel selective phosphodiesterase type 5 inhibitor, was evaluated in its first large-scale at-home trial. A total of 601 men with mild to severe erectile dysfunction (ED) were enrolled in this multi-centre, randomized, double-blind, placebo-controlled trial of 12 weeks of treatment with either placebo or 5, 10 and 20 mg of vardenafil. Primary endpoints were Q3 (vaginal penetration) and Q4 (maintenance of erection) of the International Index of Erectile Function (IIEF). In the intent-to-treat population (n=580), the changes from baseline for 5, 10 and 20 mg vardenafil (1.2, 1.3 and 1.5, respectively) were all improved (P<0.001) over placebo (0.2) for Q3 and were similarly improved for Q4 (1.4, 1.5 and 1.7) compared to placebo (0.5) (P<0.001). All vardenafil doses improved all IIEF domains compared to placebo (P<0.001). The percentage of successful intercourses was between 71 and 75% for the three vardenafil doses. For the 20 mg dose, 80% of the patients experienced improved erections (GAQ) compared to 30% for placebo. Most frequent treatment-emergent adverse events were headache (7-15%), flushing (10-11%) and up to 7% for dyspepsia or rhinitis. Vardenafil treatment resulted in a high efficacy and low adverse-event profile in a population with mixed ED etiologies.

Thirty percent of males afflicted with erectile dysfunction (ED) do not respond to oral drugs, another 15% reveal contraindications to currently available therapy, and a subset of patients actually prefer injection therapy due to its predictable short time-to-onset of erection and reliable rigidity compared to oral drugs. This paper provides both a historical and current perspective on intracavernosal therapy and reviews the popular injectable therapeutic agents that are currently used for the treatment of ED. Emphasis is placed on the efficacy, mechanism of action and side effect profiles of approved and experimental injectable pharmacotherapy for ED. International Journal of Impotence Research (2000) 12, Suppl 4, S91-S100.

From August 1978 until March 1979, 14 batches of anti-D immune globulin contaminated with hepatitis C virus (HCV) genotype 1b (20, 000-480,000 copies/dose) from a single erythrocyte donor had been administered for prophylaxis of rhesus isoimmunization throughout East Germany. All 2,867 women involved had been recalled after January 12, 1979 for repeated screening of alanine transaminase (ALT). They were prospectively followed in regional centers. We have reexamined a cohort of 1,018 women (median age 24, range 16-38 years at infection) on follow-up for 20 years in 9 representative centers. Within 6 months after anti-D administration, 10% of these women had no evidence of disease and 90% had acute hepatitis C (n = 917) including 49% with symptomatic and 22% with icteric course. After 20 years, 85% of the 917 affected women still tested positive for HCV antibodies (among them 3% responded to interferon treatment) and 55% were positive for HCV RNA (among them 7% were nonresponders to interferon and 3% were apparent HCV carriers). Only 4 (0.4%) had overt cirrhosis. Two (0.2%) died of superinfected fulminant hepatitis B or alcoholism and cirrhosis, respectively. Histology obtained in 44% of the viremic women showed hepatitis of minimal to moderate grade in 96%, portal fibrosis in 47%, and septal fibrosis in 3% of the cases. In conclusion, formerly healthy young women, without hepatic comorbidity, may clear HCV (1b) infection in half of the cases or develop mild chronic hepatitis C with low risk of progression to cirrhosis within 20 years.

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 anticteric 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.

The immunogenicity of hepatitis B vaccine is unknown for patients with chronic hepatitis C, although hepatitis B vaccination is highly recommended in these patients. We therefore studied in a prospective open trial of 59 patients with chronic hepatitis C (mean age 42 years, hepatitis C for >10 years, Child-Pugh score < or = 5) and 58 healthy hospital staff persons the rate of nonresponse (anti-HBs <10 mIU/mL at 9 months) to recombinant hepatitis B vaccine (Gen H-B-Vax(R),10 microg intradeltoidal at month 0, 1, and 6). Nonresponse was observed in 18/59 (31%) patients with chronic hepatitis C and 5/58 (9%) healthy staff persons (P <.005) (vs. 7% in historical controls; P <.005), low response (anti-HBs 10-99 mIU/mL) in 19% of patients with chronic hepatitis C and 17% of staff persons. High-dose booster vaccination led to seroconversion in 12/15 (80%) of primary nonresponders. Primary nonresponse to HB vaccine was related neither to presence of early-stage liver cirrhosis nor magnitude of serum hepatitis C virus (HCV) RNA concentration, nor explained by the presence of human leukocyte antigen (HLA) types (B8 DR3, B44, DR7, DQ2) predisposing to low antibody response to hepatitis B surface antigen. The rate of primary nonresponse to the standard regimen of recombinant hepatitis B vaccine is surprisingly high in patients with longstanding chronic hepatitis C. Therefore, the antibody to HBV surface antigen (anti-HBs) titer response should be determined in these patients. Depending on the response titer, higher booster doses may be required to achieve and maintain seroprotection in these patients.

Background: Sodium selenite may play a role in reduction of enhanced oxygen free radicals in the early phase of experimental acute pancreatitis. The aim of the study was to determine whether ERCP induced pancreatitis can be used as a human model for early acute pancreatitis and if a prophylactic antioxidant therapy with sodium selenite or a prophylactic antibiotic therapy has a beneficial effect on the clinical outcome in patients with ERCP., Patients and Methods: Sixty patients were randomly allocated in 3 groups: A (n = 20, sodium selenite i.v. 1 day before ERCP 1 mg bolus/2 x 1 mg infusion); B (n = 20, metronidazole 0.5 g/ofloxacin 0.2 g before and 6 hours after ERCP); C (n = 20, controls, no prophylaxis). Various labor parameters and physical complaints after ERCP were determined., Results: Patients with an antibiotic prophylaxis or with a sodium selenite substitution had no less physical complaints or pancreatitis than the controls. Seven patients (= 11.7%) developed a pancreatitis after ERCP. Concentration of zinc, copper, manganese, vitamin A and E did not differ significantly between the various groups., Conclusion: A prophylactic substitution with sodium selenite or prophylactic antibiotic therapy with metronidazole/ofloxacin has no beneficial effect on the clinical outcome in patients with ERCP.

The purpose of this current study was to find out the coincidence of pathological penile vascular supply with pathological data in Bulbocavernosusreflex latency (BCR-L) measurements and Pudendal Nerve SSEP (PudSSEP) recordings. Six hundred and sixty-nine males (642 with erectile dysfunction, 27 with different sexual disturbances) (mean age 49.3 y, range 17-76 y) underwent consecutively a battery of neurophysiological investigations together with pharmacotesting of cavernous bodies combined with duplex sonography of penile arteries. Pathological vascular findings were indicated in 286 men (43%), pathological neurophysiological findings in 264 men (39%). Normal findings in both investigations (vascular and neurophysiological) were encountered in 252 men (38%); 131 men (19%) revealed pathological data exclusively in the neurophysiological parameters, 153 (23%) exclusively in the vascular parameters and 133 (20%) in both. The highest percentages of pathological findings were observed in patients with diabetes mellitus (110 out of 131, 88%) and patients who had sustained pelvic trauma or surgery (36 out of 44, 82%), in contrast to the lowest percentage in patients with a proven psychogenic etiology (10 out of 38, 26%). Somewhat surprising was the rather high proportion of vascular impairment in patients with defined neurological diseases such as alcohol abuse (20 out of 51, 43%), polyneuropathy (PNP) of various etiology (9 out of 19, 47%), lumbosacral radiculopathies (26 out of 65, 40%), and CNS diseases (24 out of 52, 46%), about half of them coinciding with pathological neurophysiological findings. Even if the validity of BCR-L measurement and PudSSEP recordings in the assessment of neurogenic impotence was controversely discussed, we conclude that in a large number of impotent males both neurogenic and vascular factors are responsible for the onset of erectile dysfunction.

The clinical benefit of PGE1 in erectile dysfunction in men is well proven, while other species including non-human primates show almost no response. The reason for that difference is still unclear. We examined PGE1 binding in human surgical material (n=27) and from transsexual surgery (n=7) as well as rhesus (n=10) and cynomolgus monkeys (n=8) corpus cavernosum tissue. Erection was judged after intracavernous injection of PGE1 in men (10 microg) and in monkeys (5 microg). Human corpus cavernosum shows high- (binding capacity 24.7+/-3.3 pmol/mg protein) and low-affinity (binding capacity 77.4+/-7.3 pmol/mg protein) PGE1 binding sites. Oestrogen (3 mg/day) for more than one month before transsexual surgery decreases receptor density significantly. In rhesus and cynomolgus monkeys no high-affinity binding could be detected, while they respond on PGE1 with slight tumescence only. These findings indicate a significant correlation between corpus cavernosum PGE1 receptor density and the erectile response.