Increased Cavernosal Relaxations in Sickle Cell Mice Priapism are Associated with Alterations in the NO-cGMP Signaling Pathway

IntroductionPriapism is defined as prolonged and persistent penile erection, unassociated with sexual interest or stimulation, and is one of the many serious complications associated with sickle cell disease (SCD).AimThe aim of this study was to evaluate the role of the NO-cGMP signaling pathway in priapism in Berkeley murine model of SCD (SS).MethodsSS mice and C57BL/6 mice (control) penile tissues were removed and the erectile tissue within the corpus cavernosum (CC) was surgically dissected free. The strips were mounted in 10 mL organ baths containing Krebs solution at 37°C (95% O₂, 5% CO₂, pH 7.4), and vertically suspended between two metal hooks.Main Outcome MeasuresCumulative concentration-response curves were constructed for acetylcholine (ACh; endothelium-dependent responses), sodium nitroprusside (SNP; endothelium-independent relaxations) and BAY 41-2272 (a potent activator of NO-independent site of soluble guanylate cyclase) in CC precontracted with phenylephrine. Cavernosal responses induced by frequency-dependent electrical field stimulation (EFS) were also carried out to evaluate the nitrergic cavernosal relaxations.ResultsIn SS mice, ACh-induced cavernosal relaxations were leftward shifted by 2.6-fold (P < 0.01) that was accompanied by increases in the maximal responses (78 ± 5% and 60 ± 3% in SS and C57B6/6J mice, respectively). Similarly, SNP- and BAY 41-2272-induced CC relaxations were leftward shifted by approximately 3.3- and 2.2-fold (P < 0.01) in SS mice, respectively. A significant increase in maximal responses to SNP and BAY 41-2272 in SS mice was also observed (113 ± 6% and 124 ± 5%, respectively) compared with C57B6/6J mice (83 ± 4% and 99 ± 2%, respectively). The EFS-induced cavernosal relaxations were also significantly higher SS mice.ConclusionThese results showed that SS mice exhibit amplified corpus carvenosum relaxation response mediated by NO-cGMP signaling pathway. Intervention in this signaling pathway may be a potential therapeutic target to treat SCD priapism. Claudino MA, Franco-Penteado CF, Corat MAF, Gimenes AP, Passos LAC, Antunes E, and Costa FF. Increased cavernosal relaxations in sickle cell mice priapism are associated with alterations in the NO-cGMP signaling pathway. J Sex Med 2009;6:2187–2196.     

Exploring the Use of Exchange Transfusion in the Surgical Management of Priapism in Sickle Cell Disease: A Population-Based Analysis

IntroductionPriapism is a urologic emergency that may require surgical intervention in cases refractory to supportive care. Exchange transfusion (ET) has been previously used to manage sickle cell disease (SCD), including in priapism; however, its utilization in the context of surgical intervention has not been well-established.AimTo explore the utilization of ET, as well as other patient and hospital-level factors, associated with surgical intervention for SCD-induced priapismMethodsUsing the National Inpatient Sample (2010–2015), males diagnosed with SCD and priapism were stratified by need for surgical intervention. Survey-weighted regression models were used to analyze the association of ET to surgical intervention. Furthermore, negative binomial regression and generalized linear models with logarithmic transformation were used to compare ET vs surgery to length of hospital stay (LOS) and total hospital charges, respectively.Main Outcome Measures: Predictors of surgical intervention among patients with SCD-related priapismResultsA weighted total of 8,087 hospitalizations were identified, with 1,782 (22%) receiving surgical intervention for priapism, 484 undergoing ET (6.0%), and 149 (1.8%) receiving combined therapy of both ET and surgery. On multivariable regression, pre-existing Elixhauser comorbidities (e.g. ≥2 Elixhauser: OR: 2.20; P < 0.001), other forms of insurance (OR: 2.12; P < 0.001), and ET (OR: 1.99; P = 0.009) had increased odds of undergoing surgical intervention. In contrast, Black race (OR: 0.45; P < 0.001) and other co-existing SCD complications (e.g. infectious complications OR: 0.52; P < 0.001) reduced such odds. Compared to supportive care alone, patients undergoing ET (adjusted IRR: 1.42; 95% CI: 1.10–1.83; P = 0.007) or combined therapy (adjusted IRR: 1.42; 95% CI: 111–1.82; P < 0.001) had a longer LOS vs. surgery alone (adjusted IRR: 0.85; 95% CI: 0.74–0.97; P = 0.017). Patients receiving ET (adjusted Ratio: 2.39; 95% CI: 1.52–3.76; P < 0.001) or combined therapy (adjusted Ratio: 4.42; 95% CI: 1.67–11.71; P = 0.003) had higher ratio of mean hospital charges compared with surgery alone (adjusted Ratio: 1.09; 95% CI: 0.69–1.72; P = 0.710).ConclusionsNumerous factors were associated with the need for surgical intervention, including the use of ET. Those receiving ET, as well as those with combined therapy, had a longer LOS and increased total hospital charges.Ha AS, Wallace BK, Miles C, et al. Exploring the Use of Exchange Transfusion in the Surgical Management of Priapism in Sickle Cell Disease: A Population-Based Analysis. J Sex Med 2021;18:1788–1796.     

Penile Doppler Ultrasound in Men with Stuttering Priapism and Sickle Cell Disease—A Labile Baseline Diastolic Velocity Is a Characteristic Finding

IntroductionStuttering priapism (SP) is seen in sickle cell disease (SCD) and characterized by short‐lived painful erections. Imbalanced vascular tone is the postulated cause and this may be reflected in changes in baseline penile blood flow as measured using penile Doppler ultrasound (PDU).AimThe aim of this study was to investigate the baseline penile blood flow characteristics in men with SCD and SP, by comparing with men without SP.MethodsPDU findings were retrospectively analyzed in 100 men during flaccid state. Nine men had SP (age range 20–40 years), 4 had Peyronie's disease (PD) (35–48 years), 67 men had erectile dysfunction (16–67 years), and 20 men had normal erectile function (18–42 years).Main Outcome MeasuresThe variables measured were peak systolic and end‐diastolic velocities, and the Doppler velocity waveform. Values in men with SP were compared with those in the other groups.ResultsMedian systolic and diastolic velocity was significantly higher in men with SP (systolic/diastolic velocity was 26/4 cm/second in men with SP vs. 13/0 cm/second, 14/0 cm/second, and 16/0 cm/second in men with PD, ED, and normal erectile function, respectively; P = 0.0001). Men with SP had a characteristic low peripheral resistance (PR) waveform with fluctuating velocities; the diastolic velocity was consistently positive (2–7 cm/second) and fluctuated between +2 and +8 cm/second. In comparison, the other 91 men had high PR waveform and consistently negative diastolic velocity (range 0 to −2 cm/second).ConclusionsMen with SP had a unique baseline Doppler ultrasound waveform, with a low PR waveform and an elevated, variable cavernosal artery velocity. We propose that this may be the sonographic manifestation of a reduced, fluctuating smooth muscle tone and that PDU may have a role for diagnosis and therapeutic monitoring of SP. Patel U, Sujenthiran A, and Watkin N. Penile Doppler ultrasound in men with stuttering priapism and sickle cell disease—A labile baseline diastolic velocity is a characteristic finding. J Sex Med 2015;12:549–556.     

Clinical and Genetic Predictors of Priapism in Sickle Cell Disease: Results from the Recipient Epidemiology and Donor Evaluation Study III Brazil Cohort Study

IntroductionPriapism is the persistent and painful erection of the penis and is a common sickle cell disease (SCD) complication.AimThe goal of this study was to characterize clinical and genetic factors associated with priapism within a large multi-center SCD cohort in Brazil.MethodsCases with priapism were compared to SCD type-matched controls within defined age strata to identify clinical outcomes associated with priapism. Whole blood single nucleotide polymorphism genotyping was performed using a customized array, and a genome-wide association study (GWAS) was conducted to identify single nucleotide polymorphisms associated with priapism.Main Outcome MeasureOf the 1,314 male patients in the cohort, 188 experienced priapism (14.3%).ResultsPriapism was more common among older patients (P = .006) and more severe SCD genotypes such as homozygous SS (P < .0001). In the genotype- and age-matched analyses, associations with priapism were found for pulmonary hypertension (P = .05) and avascular necrosis (P = .01). The GWAS suggested replication of a previously reported candidate gene association of priapism for the gene transforming growth factor beta receptor 3 (TGFBR3) (P = 2 × 10^?4).Clinical ImplicationsOlder patients with more severe genotypes are at higher risk of priapism, and there is a lack of consensus on standard treatment strategies for priapism in SCD.Strengths & LimitationsThis study characterizes SCD patients with any history of priapism from a large multi-center cohort. Replication of the GWAS in an independent cohort is required to validate the results.ConclusionThese findings extend the understanding of risk factors associated with priapism in SCD and identify genetic markers to be investigated in future studies to further elucidate priapism pathophysiology.Ozahata M, Page GP, Guo Y, et al. Clinical and Genetic Predictors of Priapism in Sickle Cell Disease: Results from the Recipient Epidemiology and Donor Evaluation Study III Brazil Cohort Study. J Sex Med 2019;16:1988–1999.     

Maternal Mortality in Bahrain with Special Reference to Sickle Cell Disease

The maternal mortality in Bahrain during the 10-year period, 1977-1986, was 33.9 per 100,000 livebirths; the second 5-year period showed a significant reduction (26.9) compared to the first 5-year period (42.3). Haemorrhage, pulmonary embolism, hypertensive diseases of pregnancy and infection were the main causes of maternal mortality. Sickle cell disease was found to be an underlying cause in about one third of the maternal deaths. Avoidable factors were present in 38% of the cases, the majority being due to the failure of the patients to seek medical care or follow medical advice. Health education, premarital counselling and family planning were identified as significant factors in reducing the maternal mortality rate.     

Combination of Vacuum Erection Device and PDE5 Inhibitors as Salvage Therapy in PDE5 Inhibitor Nonresponders with Erectile Dysfunction

IntroductionOral phosphodiesterase type 5 inhibitors (PDE5i) have improved treatment options for erectile dysfunction (ED). In case of unresponsiveness to PDE5i, alternative therapies are considered.AimTo evaluate whether combination of vacuum erection device (VED) and PDE5i is effective as salvage therapy in subjects with ED in whom PDE5i alone failed.MethodsFrom September 2007 to May 2008, we evaluated 69 men (aged 36–82 years) in whom PDE5i treatment at the highest recommended dose, with at least 4–6 attempts at intercourse during a 3 months period, had failed. The clinical efficacy of combination therapy was evaluated using the International Index of Erectile Function-5 (IIEF-5) questionnaire, Sexual Encounter Profile (SEP)-2, SEP-3, and Global Patient Assessment Scale (GPAS).Main Outcome MeasuresScores on IIEF-5, SEP-2, SEP-3, and GPAS before and after combination therapy were measured.ResultsAfter 4 weeks of combination therapy, the mean IIEF-5 score increased significantly over baseline from 9.0 to 17.6 (P < 0.001). Of the 34 subjects with a SEP-2 response of “no” at baseline, 27 (79%) responded “yes” after combination therapy (P < 0.001). Of the 50 subjects with a SEP-3 response of “no” at baseline, 35 (70%) responded “yes” after combination therapy (P < 0.001). Furthermore, of the 42 subjects with a GPAS response of “not at all” or “slightly” improved at baseline, 31 (74%) responded “moderately” or “greatly” improved after combination therapy (P < 0.001). One subject (1.5%) experienced device-related intermittent penile pain, which resolved after 4 days without any action.ConclusionsStatistically significant improvements over baseline were seen in IIEF-5, SEP-2, SEP-3, and GPAS measures following 4 weeks of combination therapy of PDE5i and VED. This study supports the use of PDE5i with VED in men in whom PDE5i alone failed. This combination therapy may be offered to patients not satisfied with PDE5i alone before being switched to more invasive alternatives. Canguven O, Bailen J, Fredriksson W, Bock D, and Burnett AL. Combination of vacuum erection device and PDE5 inhibitors as salvage therapy in PDE5 inhibitor nonresponders with erectile dysfunction. J Sex Med 2009;6:2561–2567.     

Nebivolol Potentiates the Efficacy of PDE5 Inhibitors to Relax Corpus Cavernosum and Penile Arteries from Diabetic Patients by Enhancing the NO/cGMP Pathway

IntroductionThe efficacy of oral pharmacotherapy for erectile dysfunction (ED) (i.e., type 5 phosphodiesterase [PDE5] inhibitors) is significantly reduced in diabetic patients. Nebivolol is a selective β₁‐blocker used for treating hypertension that has been shown to increase the efficacy of sildenafil to reverse ED in diabetic rats.AimTo evaluate the effects of nebivolol on the efficacy of the PDE5 inhibitors, sildenafil, tadalafil, and vardenafil to relax human corpus cavernosum (HCC) and vasodilate human penile resistance arteries (HPRA) from diabetic patients with ED (DMED). The influence of nebivolol on the capacity of these three PDE5 inhibitors to stimulate cyclic guanosine monophosphate (cGMP) production in HCC was also evaluated.MethodsHCC and HPRA were obtained from organ donors without ED (NEND; n = 18) or patients with diabetes undergoing penile prosthesis implantation (DMED; n = 19). Relaxations of HCC strips and HPRA to sildenafil, tadalafil, and vardenafil were evaluated in organ chambers and wire myographs. cGMP content in HCC was determined by ether extraction and quantification by ELISA.Main Outcome MeasuresEffects of nebivolol on PDE5 inhibitor‐induced relaxation of HCC, vasodilation of HPRA and cGMP accumulation in HCC.ResultsTreatment with nebivolol (1 μM) significantly potentiated sildenafil‐, tadalafil‐ and vardenafil‐induced relaxations of HCC and vasodilations of HPRA from both NEND and DMED. Enhancement of relaxant capacity by nebivolol resulted in reversion of the impairment of PDE5 inhibition‐induced responses in DMED and it was accompanied by enhancing the ability of PDE5 inhibitors to increase cGMP in HCC restoring reduced cGMP levels in HCC from DMED.ConclusionsNebivolol potentiated the capacity of PDE5 inhibitors to relax vascular structures of erectile tissue from diabetic patients by enhancing the nitric oxide (NO)/cGMP pathway in these tissues. These effects suggest a potential therapeutic utility of nebivolol as an adjunct to PDE5 inhibitors for the treatment of ED associated with diabetes. Martínez‐Salamanca JI, La Fuente JM, Cardoso J, Fernández A, Cuevas P, Wright HM, and Angulo J. Nebivolol potentiates the efficacy of PDE5 inhibitors to relax corpus cavernosum and penile arteries from diabetic patients by enhancing the NO/cGMP pathway. J Sex Med 2014;11:1182–1192.     

Severity of ED: relationship to treatment-seeking and satisfaction with treatment using PDE5 inhibitors

IntroductionResearch in the past 20 years has demonstrated that erectile dysfunction (ED) is an area of concern for men and their partners.AimThe current study was designed to evaluate the impact of the perceived severity of ED on treatment‐seeking behavior and satisfaction with treatment among men with ED.Main Outcome MeasuresParticipants completed a questionnaire to assess the above variables, as well as the duration of ED.MethodsParticipants were 410 men with ED who were primarily recruited over the Internet via men’s health websites.ResultsThe results demonstrated that men with more severe ED compared with men with milder ED were more likely to have discussed their ED with their partner and doctor, have sought assistance for their ED problem, but they were also less satisfied with the effectiveness of phosphodiesterase type 5 inhibitors, and said they were less likely to use them in the future. Men with more severe ED were also less likely to want ED medication to last for 24 hours.ConclusionsImplications of these findings for the treatment of men with different levels of ED are discussed. McCabe M, and Matic H. Severity of ED: Relationship to treatment‐seeking and satisfaction with treatment using PDE5 inhibitors. J Sex Med 2007;4:145–151.     

Sildenafil Promotes eNOS Activation and Inhibits NADPH Oxidase in the Transgenic Sickle Cell Mouse Penis

IntroductionSickle cell disease (SCD)‐associated vasculopathy in the penis is characterized by aberrant nitric oxide and phosphodiesterase (PDE) 5 signaling, and by increased oxidative stress. Preliminary clinical trials show that continuous treatment with PDE5 inhibitor sildenafil unassociated with sexual activity decreases priapic activity in patients with SCD. However, the mechanism of its vasculoprotective effect in the penis remains unclear.AimsWe evaluated whether continuous administration of PDE5 inhibitor sildenafil promotes eNOS function at posttranslational levels and decreases superoxide‐producing enzyme NADPH oxidase activity in the sickle cell mouse penis.MethodsSCD transgenic mice were used as an animal model of SCD. WT mice served as controls. Mice received treatment with the PDE5 inhibitor sildenafil (100 mg/kg/day) or vehicle for 3 weeks. eNOS phosphorylation on Ser‐1177 (positive regulatory site), eNOS interactions with heat‐shock protein 90 (HSP90) (positive regulator), phosphorylated AKT (upstream mediator of eNOS phosphorylation on Ser‐1177), an NADPH oxidase catalytic subunit gp91(phox), and a marker of oxidative stress (4‐hydroxy‐2‐nonenal [HNE]) were measured by Western blot.Main Outcome MeasuresEffect of continuous sildenafil treatment on eNOS posttranslational activation, NADPH oxidase catalytic subunit, and oxidative stress in the penis of the sickle cell mouse.ResultsContinuous treatment with sildenafil reversed (P < 0.05) the abnormalities in protein expressions of P‐eNOS (Ser‐1177), eNOS/HSP90 interaction, P‐AKT, protein expression of gp91(phox), and 4‐HNE, in the sickle cell mouse penis. Sildenafil treatment of WT mice did not affect any of these parameters.ConclusionOur findings that sildenafil enhances eNOS activation and inhibits NADPH oxidase function in the sickle cell mouse penis offers a vasculoprotective molecular basis for the therapeutic effect of sildenafil in the penis in association with SCD. Musicki B, Bivalacqua TJ, Champion HC, and Burnett AL. Sildenafil promotes eNOS activation and inhibits NADPH oxidase in the transgenic sickle cell mouse penis. J Sex Med 2014;11:424–430.     

The role of PDE5 inhibitors in penile septal scar remodeling: assessment of clinical and radiological outcomes

IntroductionEffective oral medication for use in men with Peyronie's disease (PD) has been an area of interest of the medical community and lay public for decades. Isolated septal scars (ISS) without evidence of penile deformity is a relatively new clinical entity, and at present, there is paucity in the published literature regarding its treatment. Current research into the use of phosphodiesterase type 5 (PDE5) inhibitors in regulating penile erectile response has revealed an alternative role for PDE5 inhibitors in decreasing oxidative stress-associated inflammatory change as seen in PD.AimTo examine the presence of ISS and assess the efficacy of PDE5 inhibitor use in septal scar remodeling.MethodsRetrospective review of prospective database on all men who underwent penile Doppler ultrasound between December 2007 and December 2009.Main Outcome MeasuresOf the 65 men with ultrasonographic-confirmed ISS, 35 men received tadalafil 2.5 mg daily over a 6-month period. The clinical outcomes between the two groups were compared using International Index of Erectile Function (IIEF)-5 score and 6 months penile Doppler ultrasound follow up.ResultsThe mean age for the tadalafil group was 43.2 (20–65) years, similar to the control group at 44.2 (34–72) years. The length of time from onset to presentation was 22 (6 to 40) months. The majority of ultrasonographic-proven ISS was not clinically palpable and complaint of decreased penile rigidity (66%) was the predominant feature. Treatment with low-dose daily tadalafil did not result in any significant side effects (such as headache and flushing) or discontinuation. The tadalafil group reported higher IIEF-5 score (pretreatment 11/25 to post-treatment 18/25) (P < 0.01) and resolution of septal scar were recorded in 24 patients (69%) compared to three patients (10%) in the control group.ConclusionLow-dose daily tadalafil is a safe and effective treatment option in septal scar remodeling. Chung E, DeYoung L, and Brock GB. The role of PDE5 inhibitors in penile septal scar remodeling: Assessment of clinical and radiological outcomes.     

Physical Activity and PDE5 Inhibitors in the Treatment of Erectile Dysfunction: Results of a Randomized Controlled Study

IntroductionPhysical activity (PhA) has proven to be a protective factor for normal erectile function in numerous epidemiological studies.AimThe aim of this study was to establish if PhA could have a therapeutic role in the treatment of erectile dysfunction (ED).MethodsThis was a randomized, open-label study. A total of 60 patients complaining of ED were studied. Patients were assessed at baseline and after 3 months of study treatment. At baseline, patients were randomized to receive phosphodiesterase type 5 inhibitor (PDE5i) alone (group A) or PDE5i plus regular (≥3 hours/week), aerobic, non-agonistic PhA (group B).Main Outcome MeasuresAll subjects completed the International Index of Erectile Function (IIEF-15) questionnaire and performed total testosterone (TT).ResultsMean PhA was 3.4 hours/week in group B vs. 0.43 in group A; mean energy expenditure in group B was 1,868 kcal/ week or 22.8 metabolic equivalent (MET)/week. IIEF restoration of ED occurred in 77.8% (intervention group) vs. 39.3% (control) (P < 0.004). The IIEF-15 score resulted in statistical improvement in intervention group in all the domains but one (orgasm): erectile function 24.7 vs. 26.8 (P = 0.003); confidence (Q15) 3.53 vs. 4.07 (P = 0.006); sexual desire 6.46 vs. 7.18 (P = 0.028); intercourse satisfaction 9.85 vs. 11.25 (P = 0.001); total satisfaction 7.17 vs. 8.07 (P = 0.009); total score 56.2 vs. 61.07 (P = 0.007). TT was statistically similar in the two groups; separate analysis in each group showed statistical increase in group B 4.24 vs. 4.55 (P = 0.012). At multivariate logistic regression analysis, PhA was the only independent variable for normal erection (P = 0.010) (95% confidence interval [CI] 0.036–0.643), higher sexual satisfaction (P = 0.022) (95% CI 0.084–0.821) and normal total IIEF-15 score (P = 0.023) (95% CI 0.85–0.837).ConclusionIn this randomized controlled pilot study, PDE5i plus PhA was more effective than PDE5i alone in the treatment of ED. Maio G, Saraeb S, and Marchiori A. Physical activity and PDE5 inhibitors in the treatment of erectile dysfunction: Results of a randomized controlled study.     

Low-intensity extracorporeal shock wave therapy--a novel effective treatment for erectile dysfunction in severe ED patients who respond poorly to PDE5 inhibitor therapy

IntroductionLow‐intensity shock wave therapy (LI‐ESWT) has been reported as an effective treatment in men with mild and moderate erectile dysfunction (ED).AimThe aim of this study is to determine the efficacy of LI‐ESWT in severe ED patients who were poor responders to phosphodiesterase type 5 inhibitor (PDE5i) therapy.MethodsThis was an open‐label single‐arm prospective study on ED patients with an erection hardness score (EHS) ≤ 2 at baseline. The protocol comprised two treatment sessions per week for 3 weeks, which were repeated after a 3‐week no‐treatment interval. Patients were followed at 1 month (FU1), and only then an active PDE5i medication was provided for an additional month until final follow‐up visit (FU2).At each treatment session, LI‐ESWT was applied on the penile shaft and crus at five different anatomical sites (300 shocks, 0.09 mJ/mm² intensity at120 shocks/min).Each subject underwent a full baseline assessment of erectile function using validated questionnaires and objective penile hemodynamic testing before and after LI‐ESWT.Main Outcome MeasuresOutcome measures used are changes in the International Index of Erectile Function‐erectile function domain (IIEF‐ED) scores, the EHS measurement, and the three parameters of penile hemodynamics and endothelial function.ResultsTwenty‐nine men (mean age of 61.3) completed the study. Their mean IIEF‐ED scores increased from 8.8 ± 1 (baseline) to 12.3 ± 1 at FU1 (P = 0.035). At FU2 (on active PDE5i treatment), their IIEF‐ED further increased to 18.8 ± 1 (P < 0.0001), and 72.4% (P < 0.0001) reached an EHS of ≥3 (allowing full sexual intercourse). A significant improvement (P = 0.0001) in penile hemodynamics was detected after treatment and this improvement significantly correlated with increases in the IIEF‐ED (P < 0.05). No noteworthy adverse events were reported.ConclusionsPenile LI‐ESWT is a new modality that has the potential to treat a subgroup of severe ED patients. These preliminary data need to be reconfirmed by multicenter sham control studies in a larger group of ED patients. Gruenwald I, Appel B, and Vardi Y. Low‐intensity extracorporeal shock wave therapy—A novel effective treatment for erectile dysfunction in severe ED patients who respond poorly to PDE5 inhibitor therapy. J Sex Med 2012;9:259–264.     

原发不孕和继发不育妇女宫颈细胞衣原体抗原的测定

本文报道了使用英国CLERVIEW药盒对69例原发不孕妇女,49例继发不育妇女的宫颈细胞沙眼衣原体抗原的检测结果,结果表明:69例原发不孕妇女与49例继发不育妇女宫颈细胞沙眼衣原体感染率分别为18.75%、28.57%.继发不育组阳性率稍高.二者相比经χ~2检验,P>0.05,无显著差异.两组衣原体抗原的病例常伴有较长期的不孕史(5～8年)、反复流产史、盆腔炎、宫外孕以及低体重儿史.她们的子宫输卵管造影结果显示输卵管炎,输卵管粘连,输卵管阻塞率达82.60%.文章提示直接检测宫颈细胞上的衣原体抗原有助于分析鉴别因输卵管因素所致不育.     

人子宫颈癌裸鼠移植瘤株与细胞系的建立及其生物学特性

目的：建立人宫颈癌裸鼠体内瘤株及其相应的体外细胞系。方法：把人宫颈高分化鳞癌手术切除标本移植于裸鼠皮下，生长后行鼠间连续传代。取移植瘤行体外培养，建立相应的体外细胞系。对体内瘤株和体外细胞系进行相关的生物学检测，并行体外细胞系克隆和无血清培养。结果：历时１７个月建成人宫颈高分化鳞癌裸鼠移植瘤株ＨＣＣ－９４Ｖ，瘤株生长稳定，已传２６代，移植成瘤率为９２．９％。光镜、电镜下的形态学特征与患者肿瘤组织一致，染色体多为异倍体；多种肿瘤标记物呈高表达，癌基因蛋白产物呈低表达；人乳头状瘤病毒（ＨＰＶ）１６型呈阳性、１８型呈阴性，与患者肿瘤组织的检测结果一致。体外培养维持传代１６个月，建成人宫颈癌细胞系ＨＣＣ－９４，生长稳定，已传１３１代。电镜下显示典型的桥粒和张力原纤维结构，以及人类肿瘤异常染色体特征。细胞的肿瘤标记物及癌基因蛋白产物呈高表达。ＨＰＶ１６及１８型呈阴性。细胞裸鼠移植致瘤，其组织病理形态学与患者肿瘤组织一致，且ＨＰＶ１６呈阳性。细胞系克隆出了３个亚株，无血清培养成功。结论：ＨＣＣ－９４Ｖ和ＨＣＣ－９４是一株新的宫颈癌裸鼠移植瘤株和细胞系，为宫颈癌的进一步研究提供了理想的材料和模型。     

Dropout in the Treatment of Erectile Dysfunction with PDE5: A Study on Predictors and a Qualitative Analysis of Reasons for Discontinuation

IntroductionPhosphodiesterase type 5 inhibitors (PDE5) are currently the first line treatment for erectile dysfunction (ED). However, previous research shows that PDE5 treatments have high discontinuation rates. Understanding the reasons for discontinuing PDE5 will be necessary to optimize the response to treatment.AimThe main goals were: (i) to analyze discontinuation rate of PDE5; (ii) to identify the discontinuation predictors; and (iii) to study the reasons for discontinuation using a qualitative methodology.Main Outcome MeasuresThe PDE5 discontinuation rates, predictors, and reasons for discontinuation treatment.MethodsA total of 327 men with clinical diagnosis for ED who had been treated with PDE5 were successfully interviewed by telephone, after giving their informed consent by snail mail. Telephone interviews, concerning their ongoing treatment, were carried out using a standardized questionnaire form with quantitative and qualitative items. Participation rate was 71.8%.ResultsOf the total sample, 160 men (48.9%) had discontinued PDE5 treatment. The discontinuation rate was higher among men with diabetes (73%) and in iatrogenic group (65%), and lower in venogenic etiology (38.7%). We differentiated three groups of men who discontinued treatment (i) during the first 3 months (55.1%); (ii) between 4 and 12 months (26.9%); and (iii) after a period of 12 months (18%). Qualitative analyses revealed diverse reasons for discontinuation: non‐effectiveness of PDE5 (36.8%), psychological factors (e.g., anxiety, negative emotions, fears, concerns, dysfunctional beliefs) (17.5%), erection recovery (14.4%), and concerns about the cardiovascular safety of PDE5 (8.7%) were the most common. Older men and men whose partners were involved in the treatment, were less likely to discontinue treatment.ConclusionHalf the subjects discontinued medication. Mostly, there was a combination of factors that led to discontinuation: non‐effectiveness and psychosocial factors appear to be the main reasons. Addressing those factors will allow following up with appropriate focus on relevant topics in order to improve compliance. Carvalheira AA, Pereira NM, Maroco J, and Forjaz V. Dropout in the treatment of erectile dysfunction with PDE5: A study on predictors and a qualitative analysis of reasons for discontinuation. J Sex Med 2012;9:2361–2369.     

Adherence to Initial PDE5 Inhibitor Treatment: Randomized OpenLabel Study Comparing Tadalafil Once a Day,Tadalafil on Demand,and Sildenafil on Demand in Patients with Erectile Dysfunction

IntroductionPhosphodiesterase type 5 (PDE5) inhibitor treatment for erectile dysfunction (ED) is frequently discontinued; adherence may vary depending on the initial regimen.AimTo evaluate the effects of initiating treatment with tadalafil once a day (OaD), tadalafil on demand (pro re nata [PRN]), or sildenafil PRN on treatment adherence.MethodsIn this multicenter, openlabel study, men (≥18 years) with ED, naïve to PDE5 inhibitors, were randomized (1:1:1) to tadalafil 5 mg OaD, tadalafil 10 mg PRN, or sildenafil 50 mg PRN. An 8week randomized treatment (RT) period (dose adjustment possible) was succeeded by 16 weeks of pragmatic treatment (switches between PDE5 inhibitors allowed).Main Outcome MeasuresTreatment adherence was measured as time to discontinuation of RT (any cause), estimated by Kaplan–Meier productlimit method. Treatmentgroup differences were estimated as hazard ratio (HR; Cox proportional hazards).ResultsSeven hundred seventy patients (mean age 53 years) were randomized to tadalafil OaD (N = 257), tadalafil PRN (N = 252), and sildenafil PRN (N = 261). Kaplan–Meier estimates for patients discontinuing RT were 52.2, 42.0, and 66.7%, respectively. Median time to discontinuation of RT was significantly longer for tadalafil OaD and PRN (130 and >168 days) compared with sildenafil (67 days) (HR [97.5% confidence interval]: 0.66 [0.51, 0.85] and 0.49 [0.37, 0.65]; P < 0.001). Reasons for discontinuation with significant differences between groups (P < 0.05) included “lack of efficacy (duration of erection)” (sildenafil 9.2% vs. tadalafil OaD 4.3%, PRN 2.8%), “time constraints due to short window of action” (sildenafil 4.2% vs. tadalafil OaD 0%, PRN 0.4%), and “feel medication controls my sexual life” (sildenafil 2.7% vs. tadalafil OaD 0%). No betweengroup differences were found in International Index of Erectile FunctionErectile Function domain change from baseline to end of RT (least squares mean: 9.4–10.0, P = 0.359) or discontinuations due to adverse events (1.2–1.6%). The most common adverse event (≥4%) was headache.ConclusionsED patients assigned to tadalafil OaD or PRN adhered significantly longer to initial treatment than patients assigned to sildenafil PRN. Improvement of erectile function and safety profiles were similar in all three treatment groups.