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Biomedical subjects

Ignacio Moncada

Publications and source records attributed to Ignacio Moncada.

15 recordsLinked to original sources
PubMed2007

The influence of age on treatment outcomes in men with erectile dysfunction treated with two regimens of tadalafil: results of the SURE study.

OBJECTIVE: To evaluate whether patterns of sexual activity and efficacy over time to two dosing regimens of tadalafil differ with ageing in men with erectile dysfunction (ED). PATIENTS AND METHODS: The SURE study was a multicentre, crossover, open-label study. In all, 4262 men with ED were randomly assigned to treatment with tadalafil 20 mg on-demand before sexual activity, or three times per week for 5-6 weeks. After a 1-week washout period, patients were crossed over to the alternative regimen for 5-6 weeks. This post hoc analysis evaluated the pattern of sexual attempts, efficacy and safety of these two regimens of tadalafil across several age groups. RESULTS: The mean number of sexual attempts per week decreased from a range of 2.6-2.8 at age < or = 40 years to 1.9 at age >70 years. Age did not significantly influence the time of sexual activity after dosing. A high percentage of attempts occurred >4 h after dosing for all age groups ( approximately 70% for men taking tadalafil three times per week and approximately 50% for men taking tadalafil on-demand). For all age groups, most attempts took place in the late evening. The mean per-patient rate of successful attempts was similar for each interval up to 36 h after dosing and decreased with increasing age (> or =75% at age < or = 60 years, > or = 68% at age >60 to < or = 70 years, and > or = 60% at age >70 years). Tadalafil was well tolerated at all ages. CONCLUSIONS: Patterns of sexual activity with tadalafil 20 mg, taken on-demand or three times per week, were similar in the different age groups. Tadalafil was effective up to 36 h after dosing for all age groups.

Adolescent↗
PubMed2006

Enhanced thromboxane receptor-mediated responses and impaired endothelium-dependent relaxation in human corpus cavernosum from diabetic impotent men: role of protein kinase C activity.

We have evaluated the influence of protein kinase C (PKC) activity on penile smooth muscle tone in tissues from diabetic and nondiabetic men with erectile dysfunction. Human corpus cavernosum (HCC) strips were obtained from impotent diabetic and nondiabetic men at the time of penile prosthesis implantation and studied in organ chambers. Contractility responses to a prostanoid precursor, to prostanoids, and to the endothelium-dependent vasodilator acetylcholine were studied. Arachidonic acid (AA; 100 microM) caused cyclooxygenase-dependent relaxation of HCC. This relaxation was impaired in diabetic tissues and normalized by blocking thromboxane (TP) receptors with 20 nM [1S-[1alpha,2alpha(Z),3alpha,4alpha]]-7-[3-[[2-[(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (SQ29548). Diabetes did not affect prostaglandin (PG)E(1)-induced relaxation, but it reduced relaxation induced by the PGE(1) metabolite PGE(0). This effect was related to an interaction of PGE(0) with TP receptors. Diabetic tissues had reduced endothelium-dependent relaxation, which was partially improved by SQ29548 and completely normalized by the PKC inhibitor 3-[1-[3-(dimethylaminopropyl]-1H-indol-3-yl]-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione monohydrochloride (GF109203X; 1 microM). In HCC from nondiabetic patients, treatment with the PKC activator phorbol-12,13-dibutyrate (0.3 microM) significantly attenuated endothelium-dependent relaxation, an effect prevented by coadministration of GF109203X. Tissues from diabetic patients had enhanced sensitivity to the contractile effects of the TP receptor agonist 9,11-dideoxy-9alpha,11alpha-epoxymethano PGF(2alpha) (U46619) (EC(50) = 0.65 +/- 0.42 and 6.01 +/- 2.28 nM in diabetic and nondiabetic patients, respectively). Inhibition of PKC with 1 microM GF109203X, prevented diabetes-induced hypersensitivity to U46619-induced contractions (EC(50) = 8.55 +/- 3.12 microM). Overactivity of PKC in diabetes is responsible for enhanced contraction and reduced endothelium-dependent relaxation of HCC smooth muscle. Such alterations can result in erectile dysfunction.

Alprostadil↗
PubMed2006

Testosterone and men's quality of life.

As the worldwide population ages, the emphasis on having a reasonable quality of life in old-age is increasing. In men, age-associated testosterone decline is one of the major factors that reduce quality of life. In patients and the physicians treating them, decreased energy levels and impairments to sex-life are perceived as the most important effects of hypogonadism. Two quality of life scales, the Aging Males' Symptoms (AMS) and the Age-Related Hormone Deficiency-Dependent Quality of Life (A-RHDQoL) scales, have recently been developed to specifically assess this patient population, and the A-RHDQoL found that memory, energy and physical capabilities, and sex-life were the factors most adversely affected by low testosterone levels. Unfortunately, there are limited data on the effects of testosterone on the quality of life of men with hypogonadism, but the information that exists suggests that testosterone can improve the quality of life significantly (to the same level as men with normal testosterone levels) and the more severe the symptoms before treatment, the greater the benefits of testosterone replacement. These promising early results need to be confirmed in more detailed quality of life studies.

Aged↗
PubMed2005

An evaluation of an alternative dosing regimen with tadalafil, 3 times/week, for men with erectile dysfunction: SURE study in 14 European countries.

OBJECTIVE: To examine the preference for 2 dosing regimens (on demand or 3 times/week) for tadalafil, a phosphodiesterase 5 inhibitor with a duration of effectiveness up to 36 hours in men with erectile dysfunction (ED). DESIGN AND METHODS: SURE is a 14 European country, multicenter, crossover, and open-label study. Men with ED (N=4262) were randomized to tadalafil 20mg treatment on demand (maximum one dose per day and before sexual activity) or 3 times/week for 5-6 weeks. After a 1-week washout period, patients were crossed over to the alternate regimen for 5-6 weeks. The patient's response to a treatment preference question (TPQ) was used to determine the preferred treatment regimen. RESULTS: The mean age of the randomized patients was 55 years and 85.2% reported a history of ED for one year or greater. Overall, the responses of 3861 men to the TPQ assessment showed that 57.8% preferred the on-demand regimen and 42.2% preferred the 3 times/week dosing. Both regimens were efficacious and well tolerated. CONCLUSIONS: In this study, while 57.8% of men preferred the on-demand regimen of tadalafil 20mg, a substantial number (42.2%) preferred the 3 times/week treatment. The two regimens provide additional treatment options by giving men with erectile dysfunction unique flexibility in dosing with tadalafil.

Carbolines↗
PubMed2005

Sexual intercourse attempt patterns with two dosing regimens of tadalafil in men with erectile dysfunction: results from the SURE study in 14 European countries.

OBJECTIVE: To describe the pattern of sexual attempts by men with erectile dysfunction (ED) taking tadalafil 20 mg on demand or on an alternative dosing regimen, 3 times/week, and to assess changes in sexual behavior when the patients were exposed to the alternative regimen. DESIGN AND METHODS: Scheduled use versus on-demand regimen evaluation (SURE) is a multicenter, crossover, open-label study conducted in 14 European countries. Men with ED (N = 4,262) were randomized to tadalafil 20 mg on-demand treatment (maximum one dose per day and before sexual activity) or 3 times/week for 5-6 weeks. After a 1-week washout period, patients were crossed over to the alternative regimen for 5-6 weeks. RESULTS: Nearly half (47%) of the attempts on the on-demand regimen and 71% of the attempts on the 3 times/week treatment were performed by patients more than 4 hours post dosing. Sexual activity occurred throughout the week on both regimens, with the highest percentage of attempts made during the weekend (50% on on-demand and 48% on 3 times/week) and evening and morning hours. The efficacy of tadalafil was more than 70% mean-per-patient success rate (Sexual Encounter Profile question 3) regardless of the time interval post dosing. CONCLUSIONS: Patients on tadalafil changed their sexual behavior significantly when on an alternative dosing regimen (3 times/week) and had sexual attempts distributed over a wide period of time post dosing. A substantial number of sexual attempts were performed beyond the first 4 hours post dosing on both regimens (47% for on-demand and 71% for 3 times/week) and preferably in the evening and morning hours. Tadalafil was efficacious regardless of the time interval post dosing-i.e., up to 36 hours. The two treatment regimens, on-demand and 3 times/week, provide an additional option and unique flexibility in dosing for men with ED and their partners.

Carbolines↗
PubMed2005

Sustained efficacy and safety of vardenafil for treatment of erectile dysfunction: a randomized, double-blind, placebo-controlled study.

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.

Double-Blind Method↗
PubMed2005

[Surgical treatment of renal adenocarcinoma with venous thrombus].

OBJECTIVES: To analyze therapeutic management and survival of renal adenocarcinoma with tumor venous extension treated by surgery in our experience. METHODS: We retrospectively evaluate a series of 29 cases of renal adenocarcinoma with venous thrombus who underwent radical nephrectomy and thrombectomy from January 1986 to November 2003. Mean age was 63.4 11.9 (29-79) years. 23 patients were males (79%) and 6 (21%) females. 17 (59%) patients had the tumor in the right kidney and 12 (42%) in the left kidney. Tumor thrombus level was: Level I (renal vein-inferior vena cava) 13 (45%), Level II (infrahepatic vena cava) 9 (31%), Level III (retrohepatic vena cava/suprahepatic) 3 (10%), and Level IV (auricula) 4 (14%). 92% of the cases presented perirenal fat involvement. Survival analysis was performed including 24 cases of the 29. We analyzed overall and cancer-specific survival, as well as possible influence of tumor thrombus level, fat involvement, and tumor grade as prognostic factors. RESULTS: Mean tumor size was 8.15 +/- 2.25 cm (5-13). Surgical approach was purely abdominal in 23 cases (79%) and thoraco-phreno-laparotomy in 6 (21%). Hepatic mobilization maneuvers and hepatic pedicle clamping were performed in 5 (17%) patients. Venous clamping was: renal-cava 13 cases (44%), triple clamping I1 (37%) (9 infrahepatic and 2 suprahepatic), and supradiaphragmatic-auricula 5 (17%). Conventional extracorporeal circulation (CEC) with moderate hypothermia (26-28 degrees C) was employed in 4 cases and CEC with heart arrest (4 min) in one. Mean follow-up was 52 months. At the time of review 9 patients were alive, 11 had died from tumor and 4 had died from other causes. Mean overall survival was 71 +/- 12 months and cancer specific survival 86 +/- 14 months. Neither renal fat involvement (p=0.6) nor tumor thrombus level (p = 0.9) were prognostic factors for survival in the univariant analysis, but tumor grade was (p = 0.03). CONCLUSIONS: Patients with venous tumor extension without lymph node involvement or metastasis should be treated by radical surgery with complete excision of the tumor thrombus. Tumor grade was a prognostic factor for survival, but venous involvement level and presence of perirenal fat involvement were not.

Adenocarcinoma↗
PubMed2004

Radiological assessment of penile prosthesis: the role of magnetic resonance imaging.

Penile implants offer a dependable way of restoring erections in virtually all motivated patients. The satisfaction rate among both patients and partners using these devices is high. Advances in technology have reduced the infection rate and increased the mechanical reliability of these products. However, too often, urologists do not present this option with the same authority as other treatments. The reason is fear of complications and lack of expertise in managing them. Although they are not very frequent, complications may be catastrophic. The most significant postoperative complication associated with the implant surgery is infection of the device, which is quite frequent, but some other important complications are distal and proximal perforation of the albuginea, SST deformity, "S-shaped" deformity of the penis, erosion of a component, and mechanical malfunction of the device. The best way to manage complications is to prevent them, but we do not have many diagnostic tools available. Diagnosis is based on clinical history and physical examination, but imaging techniques are also needed to explore the prosthesis "in situ" to plan the surgical approach if it is needed. In this article we review the different imaging techniques used for the diagnosis of complications of prosthetic surgery of the penis, including conventional radiology, use of sonography, the role of CT scan and the magnetic resonance imaging (MRI) of the penile prosthesis. We conclude that MRI is the most valuable method for the diagnosis of penile prosthesis complications. It is not an ionizing radiation imaging method and has the unique feature among imaging techniques of demonstrating penile anatomy in three orthogonal planes. It is superior to any other imaging method in the definition of soft tissue contrast.

Humans↗
PubMed2004

Efficacy of sildenafil citrate at 12 hours after dosing: re-exploring the therapeutic window.

OBJECTIVE: This open-label study investigated the efficacy of sildenafil citrate at 12 hours postdose among prior treatment responders. PATIENTS AND METHODS: Eight 100-mg doses of sildenafil were provided to 40 eligible patients with erectile dysfunction (ED), who were to record the results of each sexual attempt in a patient diary. Each patient was instructed to make a sexual attempt at 1 and 12 hours postdose on 4 occasions (part 1) and only at 12 hours postdose on 4 subsequent occasions (part 2). RESULTS: Of 40 enrolled patients, 34 (85%) completed the study. In these evaluable patients, 97% and 74% of patients achieved erections that resulted in successful intercourse at 1 hour and 12 hours postdose, respectively. There was a nonsignificant reduction in the percentage of responders at 12 hours during part 1 versus part 2 of this study (71% versus 78%). CONCLUSIONS: This study demonstrates that, in the majority of these patients with ED, sildenafil remains clinically active 12 hours after administration. Larger studies may be necessary to confirm and clarify the therapeutic window of sildenafil.

Adult↗
PubMed2004

Current role of penile implants for erectile dysfunction.

PURPOSE OF REVIEW: The purpose of this review is to appraise new developments and publications in the field of penile prosthetic surgery. Urologists dealing with erectile dysfunction need to recognize the value of penile prosthetic surgery as a very efficacious treatment for this common condition. This type of surgery is needed in a considerable proportion of patients with erectile dysfunction so this review is timely and relevant. RECENT FINDINGS: The main themes in the literature covered include risk factors for infection of penile prostheses, its prevention with the use of hydrophilic and antibiotic-coated prostheses, particularly in re-operations, and its management with the new rescue procedures. Surgical tips for prosthetic surgery are also reviewed as well as clinical outcomes and factors influencing them. SUMMARY: Of all the invasive treatments currently available, placement of a penile prosthesis is one of the most successful, giving high levels of satisfaction. With the aid of new technical advances, the risk of infection--the most feared complication--can be minimized so prosthetic surgery may play a major role in the treatment of erectile dysfunction.

Erectile Dysfunction↗
PubMed2004

The penile implant for erectile dysfunction.

INTRODUCTION: Penile prostheses, introduced as the first effective organic treatment for erectile dysfunction over three decades ago, have an important role in the treatment of erectile dysfunction when other nonprosthetic treatment options have proven unsatisfactory. Although they are the least chosen and most invasive treatment option, they have the highest satisfaction rate of all available ED options and provide a predictable and reliable result. AIM: To provide recommendations/guidelines concerning state-of-the-art knowledge for utilization of the penile prosthesis in the management of men with erectile dysfunction. METHODS: An International Consultation in collaboration with the major sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various 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 2-year period. There were 10 experts from seven countries concerning the Penile Implant for Erectile Dysfunction. MAIN OUTCOME MEASURE: Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate. RESULTS: Recommendations/guidelines for penile prosthesis (hydraulic, semi-rigid and soft silicone) insertion for management of men with erectile dysfunction were updated. Consensed issues included: criteria for patient selection, informed consent procedures, strategies for preoperative preparation, operative incisions/technical considerations and outcome results in terms of patient satisfaction and device survival. Updated information was reviewed concerning therapies for device failures, device insertion in scarred corporal bodies and strategies for managing implant infections. CONCLUSIONS: There is a need for more research in developing management strategies for insertion of penile prostheses in men with ED.

Consensus↗
PubMed2004

[Methodology in infertility studies. Outcome measures for therapeutic success. When should we consider that has been a change in semen quality?].

OBJECTIVES: Surgery has been largely indicated for varicocele with the aim of improving semen parameters in male patients with subfertility or infertility. However, the criteria for therapeutic success in which its usefulness has been based on have never been clear. Our objective was to analyze current criteria for therapeutic success after surgical treatment of varicocele, studying in depth the possible influence of varicocele on semen quality, its impact on fertility, and possible advantages of treatment. METHODS: We reviewed a group of original articles, systematic reviews, and metanalysis on the issue after MEDLINE search. We mainly focus on randomized placebo-controlled prospective studies the aim of which was to evaluate the improvement in semen quality and/or pregnancy rates in subfertile/infertile couples after treatment of varicocele. CONCLUSIONS: There is great study heterogeneity, both in methods and possible interpretation of results. Although it seems treatment of varicocele may improve some semen quality parameters, it does not seem to represent an effective treatment for male subfertility.

Humans↗
PubMed2003

Diabetes impairs endothelium-dependent relaxation of human penile vascular tissues mediated by NO and EDHF.

Standard treatments for erectile dysfunction (ED) (i.e., PDE5 inhibitors) are less effective in diabetic patients for unknown reasons. Endothelium-dependent relaxation (EDR) of human corpus cavernosum (HCC) depends on nitric oxide (NO), while in human penile resistance arteries (HPRA) endothelium-derived hyperpolarizing factor (EDHF) and NO participate. Here we show that diabetes significantly reduced EDR induced by acetylcholine (ACh) in HCC and HPRA. Relaxation attributed to EDHF was also impaired in HPRA from diabetic patients. The PDE5 inhibitor, sildenafil (10nM), reversed diabetes-induced endothelial dysfunction in HCC, but not in HPRA. Calcium dobesilate (DOBE; 10 microM) fully reversed diabetes-induced endothelial dysfunction in HPRA by specifically potentiating the EDHF-mediated component of EDR. Impairment by diabetes of NO and EDHF-dependent responses precluded the complete recovery of endothelial function in HPRA by sildenafil. This could explain the poor clinical response to PDE5 inhibitors of diabetic men with ED and suggests that a pharmacological approach that combines enhancement of NO/cGMP and EDHF pathways could be necessary to treat ED in many diabetic men.

Acetylcholine↗
PubMed2003

Activation and potentiation of the NO/cGMP pathway by NG-hydroxyl-L-arginine in rabbit corpus cavernosum under normoxic and hypoxic conditions and ageing.

1 When nitric oxide synthase (NOS) produces NO from N(G)-hydroxy-L-arginine (OH-arginine) instead of L-arginine, the total requirement of molecular oxygen and NADPH to form NO is reduced. The aim of this work was to evaluate the effects of OH-arginine on the contractility of rabbit corpus cavernosum (RCC) and to compare the capacities of L-arginine and OH-arginine to enhance NO-mediated responses under normoxic and hypoxic conditions and in ageing, as models of defective NO production. 2 OH-arginine, but not L-arginine, was able to relax phenylephrine-contracted rabbit trabecular smooth muscle. OH-arginine-induced relaxation was inhibited by the NOS-inhibitor, L-NNA (300 microM), and by the guanylyl cyclase inhibitor, ODQ (20 microM), while it was not affected by the cytochrome P450 oxygenase inhibitor, miconazole (0.1 mM). Administration of OH-arginine, but not L-arginine, produced a significant increment of cGMP accumulation in RCC tissue. 3 Relaxation elicited by OH-arginine (300 microM) was still observed at low oxygen tension. The increase of cGMP levels induced by ACh (30 microM) in RCC was significantly enhanced by addition of OH-arginine (300 microM) in normoxic conditions, as well as under hypoxia, while L-arginine did not alter the effects of ACh on cGMP accumulation. 4 Endothelium-dependent and nitrergic nerve-mediated relaxations were both significantly reduced in RCC from aged animals (>20-months-old) when compared with young adult rabbits (5-months-old). Treatment with OH-arginine (300 microM) significantly potentiated endothelium-dependent and neurogenic relaxation in corpus cavernosum from aged rabbits, while L-arginine (300 microM) did not have significant effects. 5 Results show that OH-arginine promotes NO-mediated relaxation of RCC and potentiates the NO-mediated responses induced by stimulation of endogenous NO generation in hypoxic and aged tissues. We propose that the use of OH-arginine could be of interest in the treatment of erectile dysfunction, at least in those secondary to defective NO production.

Aging↗