Different effects of different phosphodiesterase type-5 inhibitors in pre-eclampsia

ObjectivesWe aimed to determine the effects of sildenafil and vardenafil in human umbilical artery preparation taken from pre-eclamptic or normal pregnant women, and also to investigate the underlying mechanisms in these effects.Study designFifteen pregnant women with pre-eclampsia and 15 healthy pregnant women were involved. Relaxation responses of sildenafil and vardenafil in the presence and absence of nitric oxide synthase inhibitor, N-[omega]-nitro-l-arginine methyl ester (l-NAME), and soluble guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), were compared between the pre-eclampsia group and the control group.ResultsSildenafil induced relaxation responses were significantly attenuated in the presence of pre-eclampsia, l-NAME and QDO. Similarly, pre-eclampsia, l-NAME or ODQ incubation also shifted vardenafil-induced relaxation responses rightward. However, in all set of experiments a maximal relaxation response was achieved by vardenafil unlike sildenafil. In conclusion vardenafil seems to relax human umbilical artery stronger than sildenafil in both pre-eclamptic and normal pregnancies.ConclusionThese data indicate that vardenafil might affect vascular responsiveness of human umbilical artery through the involvement of NO/cGMP-dependent and independent pathways while sildenafil-induced responses were seemed to be completely NO/cGMP-dependent. Further investigations are needed to clarify the mechanisms.     

How to evaluate the efficacy of the phosphodiesterase type 5 inhibitors

IntroductionSeveral methods have been so far proposed to compare the effectiveness of the three available phosphodiesterase type 5 inhibitors (PDE5Is).MethodsTwo urologists (E.C. and G.B.B.), together with the Controversy's Editor (E.A.J.), with expertise in the area of medical treatment of erectile dysfunction (ED) present the various perspectives on the evaluation of PDE5Is in ED. The use of the most popular psychometric tool, the International Index of Erectile Function, is presented by an expert psychologist (L.R.D.).Main Outcome MeasuresExpert opinion supported by the critical review of the currently available literature.ResultsTrials have demonstrated that the PDE5Is are excellent drugs with a great specificity of action and an almost perfect tolerance profile. Some instruments for comparison of clinical efficacy have to be considered subjective (psychometry, patient's preference, changes in quality of general, or sexual life). Some others are more objective (hardness, hormonal levels, and local circulation). An evidence‐based comparison of the three PDE5Is should in the future be rooted in both subjective and objective methods. This will be of paramount importance in the drug trial design of new, forthcoming PDE5Is.ConclusionsComparison between PDE5Is using both subjective and objective parameters will permit to individuate, on the basis of the evidence, the subset of couples where one drug, or one dose, or dose regimen, is to be considered of first choice. Jannini EA, DeRogatis LR, Chung E, and Brock GB. How to evaluate the efficacy of the phosphodiesterase type 5 inhibitors. J Sex Med 2012;9:26–33.     

Assessment of Obstetric and Gynecologic Food and Drug Administration Device Approvals and Recalls

Study Objective

To evaluate and compare the recall rates of obstetric and gynecologic devices approved via the Food and Drug Administration's 510(k) and premarket approval (PMA) processes.

The controversial role of phosphodiesterase type 5 inhibitors in the treatment of premature ejaculation

IntroductionIt is controversial whether or not the most frequent male sexual dysfunctions, premature ejaculation (PE) and erectile dysfunction (ED), share pathogenetic mechanisms and treatments.MethodsThree scientists (C.McM., J.C., and A.A.), together with the Controversy's Editor (E.A.J.), with expertise in the area of medical treatment of PE, present different perspectives on the use of phosphodiesterase type 5 inhibitors (PDE5is) in PE. The psychological point of view is discussed by an expert in sexology (M.P.).Main Outcome MeasureOutcome measures used are expert opinions supported by the critical review of the currently available literature.ResultsThis Controversy examines the role of nitric oxide (NO) as a neurotransmitter involved in the central and peripheral control of ejaculation, the adherence of methodology to the contemporary consensus of ideal PE drug trial design, the impact of methodology on treatment outcomes, and the role of PDE5i drugs (sildenafil, tadalafil, and vardenafil) in the treatment of PE.ConclusionsWhile it is evident that PDE5is are the first choice in patients with comorbid ED and PE (where one may be secondary to the other), well‐designed studies on the possible use of PDE5is in PE patients without ED are still limited. The issue will be less controversial when further evidence on the role of NO and PDE5 in the mechanism of ejaculation is available. Jannini EA, McMahon C, Chen J, Aversa A, and Perelman M. The controversial role of PDE5 inhibitors in the treatment of premature ejaculation. J Sex Med 2011;8:2135–2143.     

Change of erectile function and responsiveness to phosphodiesterase type 5 inhibitors at different stages of streptozotocin-induced diabetes in rats

IntroductionIt has been suggested that risk of erectile dysfunction (ED) increases with duration of diabetes and phosphodiesterase type 5 inhibitors (PDE5I) are not as effective in treatment of diabetes-associated ED. However, few studies have investigated time-dependent change in erectile function during the course of diabetes.AimTo investigate time-dependent change in erectile function and responsiveness to PDE5I in streptozotocin-induced diabetic rats and to understand the pathophysiology of diabetic ED.Main Outcome MeasuresAt 6, 8, 10, 12, and 14 weeks after diabetic induction, erectile function was assessed by cavernous nerve stimulation before and after administration of DA-8159, a novel PDE5I. Penile tissue was assessed for apoptosis with immunohistochemistry. Protein expression of Rho-kinase 2 (ROCK2), myosin phosphatase targeting subunit 1 (MYPT1), and endothelial nitric oxide synthase (eNOS) was evaluated by Western blot.MethodsStreptozotocin was injected into 50 8-week-old male Sprague-Dawley rats, which were then classified into five diabetic groups according to the observation period.ResultsDiabetic rats maintained normal erectile responses until 6 weeks of diabetes. Following 8 weeks, the rats showed lower erectile responses at higher frequencies of nerve stimulation, which were normalized to control by administration of DA-8159. In contrast, erectile responses were significantly decreased in 10-week diabetic rats, and administration of DA-8159 resulted in partial recovery of normal responses. At more than 12 weeks, rats demonstrated severe deterioration of erectile function, which did not fully respond to PDE5I. Corporal apoptosis was significantly increased after 10 weeks. Upregulation of ROCK2 was found at 6 weeks, and was followed by an increase of MYPT1 phosphorylation. Phosphorylation of eNOS showed marked suppression at 6 weeks and remained lower during the experimental period.ConclusionsImpairment of erectile function was followed by decreased responsiveness to PDE5I during the course of diabetes. The RhoA/ROCK pathway played an important role in diabetes-associated ED. Cho SY, Park K, Paick J-S, and Kim SW. Change of erectile function and responsiveness to PDE5 (Type 5 phosphodiesterase) inhibitors at different stages of streptozotocin-induced diabetes in rats.     

Racial Disparities in Response to a US Food and Drug Administration Safety Communication Regarding the Use of Power Morcellation for the Treatment of Uterine Leiomyoma

Study ObjectiveTo investigate whether the rate of increase in the performance of abdominal myomectomy over a laparoscopic approach after the US Food and Drug Administration (FDA) safety communication regarding morcellator use for myomectomy differs among races.DesignRetrospective cohort study.SettingThe American College of Surgeons National Surgical Quality Improvement data.PatientsPatients aged 18 to 55 years who underwent either laparoscopic or abdominal myomectomy, excluding malignant cases, emergency cases, operations performed by nongynecologic specialists, and cases in which myomectomy was performed during cesarean section.InterventionsNone.Measurements and Main ResultsThe odds ratios of abdominal myomectomy over laparoscopic myomectomy before and after the release of the FDA communication were calculated in 3 race categories: white, African American, and other races. In a logistic regression analysis adjusted for possible confounders, including all races, the odds ratio of abdominal myomectomy before and after the FDA communication was 1.30 (95% confidence interval [CI], 1.20–1.41; p <.001). In a logistic regression analysis with a product term of FDA communication exposure and race as a possible effect modifier, the African American population showed a significantly greater change in the odds of abdominal myomectomy over laparoscopic myomectomy in comparison with the white population (1.22; 95% CI, 1.02–1.47; p = .03). In contrast, other races showed no significant change (.83; 95% CI, .64–1.08; p = .17).ConclusionAfter the FDA communication, the odds ratio of abdominal myomectomy was disproportionately increased in the African American population.     

Breast pump adverse events: reports to the food and drug administration.

Breast pumps are medical devices used to express milk and maintain the milk supply. The purpose of this study was to characterize adverse events reported to the United States Food and Drug Administration (FDA) on breast pumps. Thirty-seven adverse event reports on breast pumps were identified from the Manufacturer and User Facility Device Experience database between 1992 and 2003. Four additional reports were found in the Device Experience Network database from 1992 to 1996. The most commonly reported adverse events for electric breast pumps were pain, soreness, or discomfort; the need for medical intervention; and breast tissue damage. Most frequently reported problems for manual breast pumps were breast tissue damage and infection. Contamination of breast milk during pumping was also reported. Breast pump adverse events are likely underreported to the FDA. Reporting adverse events is important for improving the design and manufacture of breast pumps and subsequently decreasing adverse events.