A therapeutic confirmatory study to assess the safety and efficacy of Zydena (udenafil) for the treatment of erectile dysfunction in male patients with diabetes mellitus

IntroductionPatients with diabetes mellitus (DM) are reported to experience more severe erectile dysfunction (ED) symptoms and respond less to ED treatments compared with patients with ED of other etiologies.AimThis study was undertaken to evaluate the safety and efficacy of udenafil for the treatment of ED in a larger number of patients with DM.MethodsA placebo‐controlled, randomized, double‐blind, double‐dummy, parallel‐group design multicenter study, fixed‐dose trial was conducted. The trial involved seven study sites in Korea, with 174 ED patients with DM. The subjects, treated with placebo, 100 mg, or 200 mg of udenafil for 12 weeks, were asked to complete the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) diary, and the Global Assessment Question (GAQ) during the study period.Main Outcome MeasuresThe primary efficacy parameter was the change in the erectile function domain (EFD) score of IIEF from baseline. Secondary parameters were IIEF questions 3 (Q3) and Q4, SEP Q2 and Q3, rate of achieving normal erectile function (EFD ≥ 26), and the response to GAQ.ResultsCompared with the placebo, patients receiving both doses of udenafil showed statistically significant improvements in the IIEF‐EFD score, respectively. However, statistically significant difference was not observed between the udenafil 100 mg and the udenafil 200 mg groups. Similar results were observed in the comparison of Q3 and Q4 of IIEF, SEP diary, and GAQ. The percentages of subjects experiencing at least one adverse event related to the study drugs were 3.6%, 15.8%, and 22.4% for the placebo, udenafil 100 mg, and udenafil 200 mg groups, respectively. However, these events were all mild in severity. Major adverse events were flushing, headache, nausea, and conjunctival hyperemia.ConclusionUdenafil was significantly effective for the treatment of ED, demonstrating statistically significant improvement in erectile function in patients with DM. The incidence of adverse events was relatively low and well tolerated in patients with DM. Moon DG, Yang DY, Lee CH, Ahn TY, Min KS, Park K, Park CK, and Kim JJ. A therapeutic confirmatory study to assess the safety and efficacy of Zydena^® (udenafil) for the treatment of erectile dysfunction in male patients with diabetes mellitus. J Sex Med 2011;8:2048–2061.     

Apocrine poroma with sebaceous differentiation

Poromas have been classified as eccrine neoplasms, but several recent reports of poroid tumors with sebaceous, follicular, and apocrine differentiation have challenged this concept. We report a case of apocrine poroma with sebaceous differentiation. A 69-year-old man presented with an asymptomatic elevated erythematous plaque. Histopathology revealed cellular nests composed of cuboidal poroid cells and sebocytes. The nests varied in size and were entirely intraepidermally arranged in a growth pattern similar to that of hidroacanthoma simplex. Given the common embryologic origin of folliculosebaceous and apocrine units, we believe that this lesion represents an apocrine poroma with sebaceous differentiation.     

THE DISTRIBUTION OF MELANOCYTIC NAEVI IN MELANOMA PATIENTS AND CONTROL SUBJECTS

A study of 121 melanoma patients and 139 control subjects was conducted among whites to examine and compare the distribution of non-dysplastic and dysplastic naevi and other pigmented lesions in each group. Melanoma patients had a mean of 97 melanocytic naevi which were greater than 2 mm in diameter and controls had a mean of 36 such naevi, while the medians were 58 and 22 respectively (p less than 0.0001). 55% of melanoma patients and 17% of controls had at least one clinically determined dysplastic naevus, and 26% of melanoma patients and 6% of controls had at least 5 dysplastic naevi. Men were found to have more naevi on the trunk than women in both melanoma cases (p = 0.01), and controls (p = 0.005). Dysplastic naevi were most often found on the trunk and were present at this location in 51% of cases and 17% of controls. Melanoma patients and control subjects with dysplastic naevi, when compared to those without these lesions, had larger number of non-dysplastic naevi. Lentigines were more common among melanoma patients that among control subjects (p = 0.02). There were no differences in the number of non-dysplastic naevi among cases with light and dark hair and eyes, or among controls with these characteristics. There also was little variation in the number of naevi according to number of blistering sunburns.     

Gender-related difference in left ventricular diastolic elastance during exercise in patients with diabetes mellitus

Background Because the ratio of mitral inflow and annular velocity to stroke volume has been reported as an index of diastolic elastance (Ed), the hypothesis tested in the present study was that Ed during exercise would be more abnormal in female than in male patients with type 2 diabetes. Methods and Results Ed was measured at rest and during graded supine bicycle exercise (25W, 3-min increments) in 53 patients (27 males, mean age 53+/-14 years) with type 2 diabetes and 53 age- and gender-matched controls. The patients with diabetes were divided into 2 groups by gender. Ed was not significantly different at rest between men and women, but was significantly higher during exercise in women than in men (25 W, 0.15+/-0.04 vs 0.20+/-0.07, p=0.009; 50 W, 0.16+/-0.05 vs 0.21+/-0.08, p=0.0175). Conclusion Left ventricular (LV) diastolic elastance is abnormal during exercise, but not at rest, in patients with diabetes without overt heart disease. Female gender was associated with increased LV stiffness during exercise among patients with type 2 diabetes. (Circ J 2008; 72: 1443 - 1448).     

Glial cytoplasmic inclusions in neurologically normal elderly: prodromal multiple system atrophy?

In this study, we used immunohistochemistry to screen for alpha-synuclein pathology in the brains of 241 individuals without clinical evidence of neurologic disease, and discovered 36 cases (15%) with incidental Lewy bodies (LBs) and one case, a 96-year-old woman (0.4%), with inclusions similar to those seen in multiple system atrophy (MSA), a non-familial neurodegenerative disorder characterized by parkinsonism, cerebellar ataxia and autonomic dysfunction and alpha-synuclein immunoreactive glial cytoplasmic inclusions (GCI). In a routine hospital autopsy series of 125 brains, we detected GCI in a neurologically normal 82-year-old man (0.8%). Both cases showed widespread GCI in the central nervous system, as well as a few neuronal cytoplasmic inclusions, but no neuronal loss or gliosis in vulnerable brain regions, including the substantia nigra, putamen, inferior olive and pontine base. Applying a recently proposed grading scale for MSA, the two cases showed pathology far below that detected in patients with clinically overt MSA, suggesting the possibility that these two individuals had preclinical MSA. The prevalence of clinically overt MSA is estimated to be about 4 per 100,000 persons (0.004%), which is far less than the frequency of GCI in this series (0.4-0.8%). Further studies are needed to determine if GCI in neurologically normal elderly represents prodromal MSA or a rare non-progressive age-related alpha-synucleinopathy.     

Normoxic ventilatory resuscitation following controlled cortical impact reduces peroxynitrite-mediated protein nitration in the hippocampus

OBJECTIVES: Ventilatory resuscitation with 100% O2 after severe traumatic brain injury (TBI) raises concerns about the increased production of reactive oxygen species (ROS). The product of peroxynitrite-meditated tyrosine residue nitration, 3-nitrotyrosine (3-NT), is a marker for oxidative damage to proteins. The authors hypothesized that posttraumatic resuscitation with hyperoxia (100% fraction of inspired oxygen [FiO2] concentration) results in increased ROS-induced damage to proteins compared with resuscitation using normoxia (21% FiO2 concentration). METHODS: Male Sprague-Dawley rats underwent controlled cortical impact (CCI) injury and resuscitation with either normoxic or hyperoxic ventilation for 1 hour (5 rats per group). Twenty-four hours after injury, rat hippocampi were evaluated using 3-NT immunostaining. In a second experiment, animals similarly underwent CCI injury and normoxic or hyperoxic ventilation for 1 hour (4 rats per group). One week after injury, neuronal counts were performed after neuronal nuclei immunostaining. RESULTS: The 3-NT staining was significantly increased in the hippocampi of the hyperoxic group. The normoxic group showed a 51.0% reduction of staining in the CA1 region compared with the hyperoxic group and a 50.8% reduction in the CA3 region (p < 0.05, both regions). There was no significant difference in staining between the injured normoxic group and sham-operated control groups. In the delayed analysis of neuronal survival (neuronal counts), there was no significant difference between the hyperoxic and normoxic groups. CONCLUSIONS: In this clinically relevant model of TBI, normoxic resuscitation significantly reduced oxidative damage to proteins compared with hyperoxic resuscitation. Neuronal counts showed no benefit from hyperoxic resuscitation. These findings indicate that hyperoxic ventilation in the early stages after severe TBI may exacerbate oxidative damage to proteins.