The future of erectile dysfunction (ED)

About 30-40 % of ED patients are non-responders to PDE 5 inhibitor monotherapy. Lifestyle modifications and physical activity with weight loss enhance PDE 5 inhibitor responsiveness. The same applies for combination therapies such PDE 5 inhibitors + L-Arginine 3.000mg, PDE 5 inhibitors + statins and PDE 5 inhibitors + Yohimbine. Combination of daily dosing with Tadalafil 5 mg and on demand application of sildenafil or vardenafil can improve responsiveness and erection hardness (personal experiences). Guanylate cyclase activators or RhoA-kinase inhibitors, either as monotherapy or in combination with PDE 5 inhibitors have shown in preclinical settings the potential to improve erectile function and represent targets for new ED drugs in the future. Immunophilin ligands were able to ameliorate erectile function after cavernous nerve injury due to pelvic surgery. Although having shown convincing efficacy both in animals and humans the centrally acting Melanocortin Receptor (MCR) Agonists were given up for ED treatment because of unfavorable side-effects.Promising targets for ED therapy in the future is gene therapy with several targets as well as stem cell therapy with adipose-derived or muscle-derived stem cells.     

Penile revascularization in vasculogenic erectile dysfunction (ED): long-term follow-up

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? This study reflects the second largest series of revascularization operations performed in different etiologic and risk groups with the longest follow up. Beyond that this is the only study in which CC‐EMG techniques were used preoperatively to exclude some patients and to predict postoperative success in penile revascularization.

OBJECTIVE

? To determine the overall long‐term success of penile revascularization surgery in the treatment of vasculogenic erectile dysfunction (ED) and also to investigate the effect of risk factors on the results of a modified Furlow–Fisher technique.

PATIENTS AND METHODS

? Between 1999 and 2010, 125 men with a mean (sd , range) age of 43.2 (11.3, 23–69) years underwent penile revascularization surgery. In all, 110 men completed the long‐term follow‐up with a mean follow‐up of 73.2 months. ? Diagnostic evaluations, penile colour Doppler ultrasonography, corpus cavernosum electromyography, and cavernosometry, were performed in all the men before surgery. ? The efficacy of the surgery was assessed as improvement or failure according to the change in the five‐item version of the International Index of Erectile Function (IIEF‐5). A ≥5 point increase in the IIEF‐5 score during the latest patient visit after surgery compared with that before surgery was regarded as improvement (surgical success).

RESULTS

? The mean (sd ) IIEF‐5 score was 7.3 (3.2) before surgery and at the end of the follow‐up periodit was 16.8 (3.1). ? The success rates were 81.8% at 3 months, 77.2% at 1 year, 70% at 2 years, 66.3% at 3 years and 63.6% at 5 years after surgery in the men who achieved a no‐ED threshold score of >26 in the IIEF‐15. ? The success rate was the highest in the men with no risk factors (92.8%). ? Seven patients (6.36%) showed signs of glans hypervascularization as a major complication.

CONCLUSIONS

? Penile revascularization surgery has not been widely used by urologists probably due to the technical difficulties and the use of phosphodiesterase type 5 inhibitors. ? However, with reported high rates of noncompliance or failure of oral pharmacotherapy it seems likely that this surgery will become more popular in the near future.     

癫痫患者维库溴铵ED95的测定

目的 测定癫痫患者维库溴铵ED(95)值.方法 选取择期癫痫手术患者50例,ASA Ⅰ或Ⅱ级,年龄16～43岁,病史3～26年.患者均有服用抗癫痫药物史,术前均无酸碱平衡及水电解质紊乱,心肺、肝肾功能正常,随机均分为5个剂量组,维库溴铵剂量分别为20、30、40、50、60 μg/kg.记录拇内收肌四个成串刺激第一次反应最大抑制的百分率并进行概率单位转换,将维库溴铵的首次剂量进行对数转换,用直线回归方法建立维库溴铵的剂量-反应曲线,并记录起效时间.结果 癫痫患者维库溴铵ED(95)为57.2 μg/kg,95%可信区间(CI)53.8～63.6 μg/kg.结论 癫痫患者维库溴铵ED(95)为57.2 μg/kg(95% CI 53.8～63.6 μg/kg),明显大于非癫痫患者.     

Animal models of erectile dysfunction (ED): potential utility of non-human primates as a model of atherosclerosis-induced vascular ED

Erectile dysfunction (ED) is a prevalent medical condition affecting 18 million men and their sexual partners in the United States alone. In the majority of patients, ED is related to alterations in the flow of blood to or from the penis. Undeniably, significant progress has been made in understanding the multifactorial mechanisms that modulate erectile capacity and predispose one to ED, and this, in turn, has led to the availability of more effective treatment options. Nonetheless, all current therapies have untoward side effects, and moreover, there are still no satisfactory treatments for many patients with ED. Further enhancements in the treatment of ED would logically result from both early intervention and more detailed mechanistic insight into the characteristics of the disease process per se. This fact underscores the importance of improved understanding of the initiation, development and progression of ED. However, to do so requires longitudinal studies on animal models that more closely approximate the corresponding clinical features and time course of human disease. The goal of this report is twofold. First, to provide a brief general overview of the applicability of commonly used animal models for the study of ED. The second and primary goal is to highlight the scientific rationale for using non-human primates to evaluate the impact of atherosclerosis-induced vascular disease on the penile and systemic circulatory systems. This latter goal seems especially relevant in light of the recent literature documenting a link between ED and systemic vascular disease, a finding that has major implications in an aging US male population consuming a high fat diet.     

Erectile dysfunction (ED) is prevalent, bothersome and underdiagnosed in patients consulting urologists for benign prostatic syndrome (BPS)

OBJECTIVES: The aim of the present study was to determine the prevalence of erectile dysfunction (ED) in patients visiting office-based urologists in Germany because of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), and to evaluate the impact of ED on quality of life (QoL) in these patients. METHODS: 500 office-based urologists in Germany were invited to evaluate 20 consecutive patients for erectile dysfunction, who presented because of BPH-related LUTS. Physicians provided information on demographic factors, duration and treatment history of BPH, severity of LUTS, ED risk factors, and assessed the patient for the clinical diagnosis of ED. Patients were asked to complete the German version of the IPSS to measure LUTS severity. ED-patients quantified erectile dysfunction and impact on quality of life with validated German questionnaires (Cologne assessment of male erectile dysfunction KEED, and Qol-Med). RESULTS: Office-based urologists were aware of ED in 37.3% of 8768 patients presenting for LUTS before the study, 14.7% of patients were treated for ED. After the study-related assessment, physicians diagnosed ED in 62.1% of these patients and planned treatment in 46.9%. Severity of LUTS and ED prevalence correlated significantly after age-stratification. The incidence of ED was increased in patients with established ED risk factors. Mean QoL-Med score (best QoL: 100, worst QoL: 0) was 53.8 in patients with ED and 50.1 in ED-patients considering treatment. CONCLUSION: ED is highly prevalent in LUTS patients visiting an office-based urologist and is accompanied by a profound impact on the quality of life. Apparently, even during an urological consultation many ED-patients are hesitant to actively ask for treatment. Sexual issues should become key considerations for physicians managing patients with LUTS, especially since effective and well established oral treatment for ED is available.     

Determination of the median effective dose (ED50) of spinal chloroprocaine in labour analgesia

The primary goal of this study was to determine the median effective dose (ED₅₀) of spinal chloroprocaine for labour analgesia. Thirty‐eight parturients requesting neuraxial analgesia were enrolled. Doses of 1% chloroprocaine were determined by the technique of up–down sequential allocation, with an initial dose of 20 mg and steps of 2 mg. The chloroprocaine spinal dose was given as the spinal component of a combined spinal‐epidural, which was then supplemented with an epidural dose of 7.5 μg sufentanil in 7 ml saline. Effective analgesia was defined as a score ≤ 10 mm within 15 min on a 100‐mm visual analogue pain scale. Using the isotonic regression estimator method, the ED₅₀ of chloroprocaine for the spinal component of a combined spinal‐epidural for labour was calculated to be median (95%CI) 12.0 (9.3–17.0) mg.     

Determination of the median effective dose (ED50) of bupivacaine and ropivacaine unilateral spinal anesthesia

Background

Unilateral spinal anesthesia (USpA) has been reported to potentiate spinal anaesthesia and is used in geriatric patients. The purpose of this study was to determine the median effective dose (ED₅₀) of 0.5% hypobaric bupivacaine and 0.5% hypobaric ropivacaine USpA for geriatric patients (age ≥ 70 years) undergoing elective hip replacement surgery.

Methods

A total of 60 geriatric patients (age ≥ 70 years) undergoing elective hip replacement surgery were enrolled in this study. The patients were randomized into 2 groups to receive either intrathecal 0.5% hypobaric bupivacaine USpA (group B) or 0.5% hypobaric ropivacaine USpA (group R). Effective anesthesia was defined as a T10 sensory blockade level maintained for more than 60 min, and a Bromage score of 3 on the operation side within 10 min after injection with no additional epidural anesthetic required during surgery. The ED₅₀ of 0.5% hypobaric bupivacaine and 0.5% hypobaric ropivacaine was calculated using the Dixon and Massey formula.

Results

No significant differences were found between the two groups in terms of demographic data. The ED₅₀ of 0.5% hypobaric bupivacaine USpA was 4.66 mg (95% confidence interval CI 4.69–4.63 mg) mg and that of 0.5% hypobaric ropivacaine USpA was 6.43 mg (95% CI 6.47–6.39 mg) for geriatric patients undergoing hip replacement surgery.

Conclusion

We find the ED₅₀ were lower, and the ED50 of 0.5% hypobaric bupivacaine and ropivacaine was 4.66 mg (95% CI 4.69–4.63 mg) and 6.43 mg (95% CI 6.47–6.39 mg), respectively, for USpA in geriatric patients (age ≥ 70 years) undergoing elective hip replacement surgery.

     

Age influences the minimum infusion rate (ED50) for continuous infusions of Althesin and methohexitone

The influence of age has been studied on equipotent rates of continuous infusions of two intravenous hypnotic agents. Two end points have been defined; ED50: the rate needed to suppress the initial response to the surgical incision in 50% of patients, and ED95: the corresponding rate in 95% of patients receiving continuous infusion anaesthesia to supplement 67% nitrous oxide in oxygen. All 210 patients included in the study were premedicated with morphine 0.15 mg kg-1. For patients aged 20-40 years (young group), the ED50 values for Althesin (as alphaxalone) and methohexitone were 14.6 micrograms kg-1 min-1 and 59.9 micrograms kg-1 min-1. The ED95 values were 21.0 micrograms kg-1 min-1 and 92.1 micrograms kg-1 min-1. For patients aged 55-80 years (old group), the ED50 values for Althesin and methohexitone were 11.0 micrograms kg-1 min-1 and 44.2 micrograms kg-1 m in-1, while the corresponding ED95 values were 16.4 micrograms kg-1 min-1 and 76.2 micrograms kg-1 min-1.     

The correlation between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED): results from a survey in males from Mexico City (MexiLUTS)

Introduction

ED and LUTS affect a high proportion of male population. Although Hispanics are suspected to have a higher risk of experiencing LUTS, detailed information on its frequency and association with ED in this population is scarce.

Objective

To determine the frequency of LUTS and ED, and its correlation in Mexican males.

Methods

A cross-sectional analytical survey was answered by 1041 men. It included the International Prostate Symptom Score and the quality of life question (IPSS/QoL); International Index of Erectile Function (IIEF-5); the short form of the International Consultation of Incontinence Questionnaire (ICIQ-SF); and demographic data. For the analysis, we divided our population into 2 groups (18–39 and 40 and older), and then an exploratory correlation analysis was performed to search for significant differences among IPSS severity groups, and finally a multivariate regression model was applied.

Results

Mean age was 48.6 ± 14.5 years. One hundred twenty-three individuals (11.8 %) were asymptomatic, and 611 (58.7 %) had mild, 226 (21.7 %) had moderate, and 81 (7.8 %) had severe IPSS score. The most common symptoms were nocturia (72.4 %), increased urinary frequency (58.3 %), and slow urinary stream (42.6 %). Two hundred fifty-eight (24.7 %) complained of incontinence. Of 765 individuals, 484(63.2 %) reported some degree of ED. Severe LUTS, DM, and age were independent risk factors for ED severity.

Conclusion

LUTS and ED may represent one of the largest sources of morbidity in our population, and their association was demonstrated. Awareness on these entities should be raised, and further research is required to determine the higher frequency of LUTS and ED in Hispanics.

     

Endoscopic contact Nd:YAG laser resectional vaporization (ECLRV) and esophageal dilatation (ED) in advanced malignant obstruction of the esophagus.

Malignant esophageal obstruction in patients with advanced and metastatic carcinoma is unsuitable for surgery. Palliative treatment must provide adequate swallowing with minimum complications in these often seriously ill patients. Twenty consecutive patients underwent endoscopic Nd:YAG contact laser resection and vaporization (ECLRV) and esophageal dilatation (ED) for advanced esophageal carcinoma since August, 1985. Average duration of the disease when first referred was 7.2 months. Tumor cell type was either squamous cell carcinoma (n = 11) or adenocarcinoma (n = 9). Tumor location was distal (n = 14), middle (n = 5), or upper (n = 2). Mean tumor length was 7.5 cm. Mean preoperative luminal diameter was 1 mm, with total obstruction in ten (50%) patients. The operative procedure in all patients was under general anesthesia with endotracheal tube intubation. Rigid and flexible endoscopes were both used as indicated. Mean postoperative luminal diameter was 15 mm. All but four were able to swallow fluids on the first postoperative day, followed by semisolids the next day without discomfort. Minor perforation was noted in three cases and managed in two conservatively. One more patient had difficulty in swallowing due to extra-esophageal compression, in spite of a technically successful laser therapy. Percutaneous endoscopic gastrostomy (PEG) was carried out in eight cases. Eleven patients were retreated successfully for recurrent obstruction and two were treated more than twice, at a mean of six-week intervals. Endoscopic contact laser resectional vaporization with esophageal dilatation was relatively safe and provided an improved quality of life in this preliminary study group, providing a mean survival of 18.5 weeks (range 2-50 weeks).     

Intrathecal sufentanil decreases the median effective dose (ED50) of intrathecal hyperbaric ropivacaine for caesarean delivery

Background: The addition of opioid to local anaesthetics has become a well‐accepted practice of spinal anaesthesia for caesarean delivery. Successful caesarean delivery anaesthesia has been reported with the use of a low dose of intrathecal hyperbaric ropivacaine coadministered with sufentanil. This prospective, double‐blinded study determined the median effective dose (ED50) of intrathecal hyperbaric ropivacaine with and without sufentanil for caesarean delivery, to quantify the sparing effect of sufentanil on the ED50 of intrathecal hyperbaric ropivacaine. Methods: Sixty‐four parturients undergoing elective caesarean delivery with combined spinal–epidural anaesthesia were randomized into two groups: Group R (ropivacaine) and Group RS (ropivacaine plus sufentanil 5 μg). The initial dose of ropivacaine was 13 mg in Group R and 10 mg in Group RS. The effective dose was defined as a T₆ level attained within 10 min and no supplemental epidural anaesthetic required during surgery. Effective or ineffective responses determined, respectively, a 0.3 mg decrease or increase of the dose of ropivacaine for the next patient using an up–down sequential allocation. Results: The ED50 of intrathecal ropivacaine was 11.2 mg [confidence interval (CI) 95%: 11.0–11.6] in Group R vs. 8.1 mg (CI 95%: 7.8–8.3) in Group RS. Motor block was markedly more intense in Group R than in Group RS, and the incidence of shivering was lower in Group RS than in Group R. There were no differences in the onset time of sensory block or motor block, in the incidence of hypotension, nausea and vomiting. Conclusion: Intrathecal sufentanil 5 μg produced a 28% reduction of ED50 of intrathecal hyperbaric ropivacaine for caesarean delivery.     

Apomorphine SL (Uprima): preclinical and clinical experiences learned from the first central nervous system-acting ED drug

An exclusive central site of action for the proerectile effect of apomorphine, including not only the brain but also the spinal cord, is supported by extensive experimental data. Assuming that the mechanisms of action of apomorphine are similar in humans and animal models, its use for the treatment of erectile dysfunction (ED) validates the emerging idea that erectile response could be enhanced by acting directly within the central nervous system (CNS). It also emphasized the key role of the dopaminergic system in the control of erection. As exemplified with the clinical development of apomorphine, targeting the CNS does not rule out the occurrence of undesirable side effects. Because the rare event of syncope induced by apomorphine is not well understood, further research should be conducted to explore its possible mechanisms. In clinical practice, however, approved doses of apomorphine SL are well tolerated. It is noteworthy that no modification of sexual desire was observed with apomorphine. Indeed, drugs acting within the CNS may more likely interact with sexual desire than peripherally acting drugs, and care should be taken to assess this point in the future. Although our knowledge of the control of penile erection by the CNS is restricted, there are many potential sites for CNS-acting ED drugs. New centrally acting therapy for ED should concentrate on receptor targets more specific to erectile command. Clinical efficacy of new centrally-acting compounds will assess the well-founded purpose of this rationalization.     

Epidural test dose with levobupivacaine and ropivacaine: determination of ED(50) motor block after spinal administration

Background. When a test is required to detect a possible intrathecalcatheter, many would seek to use the same local anaestheticas that used for epidural analgesia. The rapid onset of inappropriatemotor block after a local anaesthetic administered epidurallyimplies intrathecal spread. Because of claims of greater sensory–motorseparation, or because of reduced potency compared with bupivacaine,the efficacy of the new local anaesthetics in intrathecal testinghas been questioned. The aim of this study was to establishthe feasibility of a test dose for an inadvertent intrathecalcatheter using ropivacaine and levobupivacaine, and to establishthe dose required. Methods. Sixty women undergoing elective Caesarean section witha combined spinal– epidural technique were enrolled intothis prospective, double-blind sequential allocation study.The women were randomized to receive plain levobupivacaine 0.5%or ropivacaine 0.5% intrathecally. The dose was determined accordingto up–down sequential allocation. The end-point was anyevidence of lower limb motor block within 5 min of injection. Results. The ED₅₀ motor block at 5 min was 4.8 mg (95% CI, 4.49,5.28) for levobupivacaine and 5.9 mg (95% CI, 4.82, 6.98) forropivacaine (95% CI difference, 0.052, 1.98) (P=0.04). The estimatedED₉₅ motor block was 5.9 mg (95% CI 5.19, 6.71) for levobupivacaineand 8.3 mg (95% CI, 6.30, 10.44) for ropivacaine. The potencyratio between the two drugs was 0.83 (95% CI, 0.69, 0.99). Conclusions. Both local anaesthetics produce evidence of motorblock within 5 min of intrathecal injection and could serveas tests of intrathecal administration. Derived ED₉₅ valuessuggest 10 mg doses should be effective, but this study didnot measure predictive value. Ropivacaine is less potent formotor block than levobupivacaine by a factor of 0.83 (P<0.04). Br J Anaesth 2004; 92: 850–3