Improvement in the ability to have sex in patients with Peyronie's disease treated with Collagenase Clostridium histolyticum

Objective: To describe the results of intralesional Collagenase Clostridium histolyticum (CCH) treatment in patients with Peyronie's disease (PD) in real-world setting. PD is characterized by curvature of the erect penis caused by fibrotic tissue in the tunica albuginea.Patients and methods: Patients with stable PD and curvature of 30° to 90° were prospectively enrolled. CCH injections were initially given using a scheme of four cycles of two injections within 48–72 h every 6 weeks. Later using a modified scheme of three injections every 4 weeks, combined with a vacuum erection device (VED) twice daily. All patients were requested to take pictures of the erect penis prior to and following treatment, from above and laterally. Curvature was measured by three independent researchers based on the provided pictures using a goniometer. Furthermore, patients filled in the Peyronie Disease Questionnaire-NL (PDQ-NL) and Patient Reported Outcome Measurement (PROM).The primary outcome was reduction in curvature and the ability to have penetrating sex again. Secondary outcomes include pain scores during injections, changes in PDQ-NL, PROM and complications of CCH treatment.Results: Sixty-three patients were included, mean age was 56.0 years (range 39–70) and mean reduction in curvature 20.6° (SD 10.2, range 5–49); 74.5% of the patients were able to have penetrating sex again following treatment, compared with 41.2% prior to treatment. According to the PROM questions, sexual improvement was seen in 66.7% of patients. The satisfaction rate was 6.8 (SD 1.8). All patients save two recommend treatment.Conclusions: Intralesional treatment with CCH in men with PD leads to a mean curvature improvement of 20.6°. Following treatment, 74.5% of men were able to have sexual intercourse and 54.9% of the couples were satisfied with their sex life. No major complications occurred in the patients treated with CCH. CCH is not available in Europe anymore despite good results.</p

ARF1·GTP, Tyrosine-based Signals, and Phosphatidylinositol 4,5-Bisphosphate Constitute a Minimal Machinery to Recruit the AP-1 Clathrin Adaptor to Membranes

At the trans-Golgi network, clathrin coats containing AP-1 adaptor complexes are formed in an ARF1-dependent manner, generating vesicles transporting cargo proteins to endosomes. The mechanism of site-specific targeting of AP-1 and the role of cargo are poorly understood. We have developed an in vitro assay to study the recruitment of purified AP-1 adaptors to chemically defined liposomes presenting peptides corresponding to tyrosine-based sorting motifs. AP-1 recruitment was found to be dependent on myristoylated ARF1, GTP or nonhydrolyzable GTP-analogs, tyrosine signals, and small amounts of phosphoinositides, most prominently phosphatidylinositol 4,5-bisphosphate, in the absence of any additional cytosolic or membrane bound proteins. AP-1 from cytosol could be recruited to a tyrosine signal independently of the lipid composition, but the rate of recruitment was increased by phosphatidylinositol 4,5-bisphosphate. The results thus indicate that cargo proteins are involved in coat recruitment and that the local lipid composition contributes to specifying the site of vesicle formation

THE PLURALITY OF FACTORS INFLUENCING POLICYMAKINC: SCHOOL REFORM LEGISLATION IN THE AMERICAN STATES, 1982-84

This paper attempts to explore recent efforts of American state legislatures to improve the quality of public schools. Which state legislatures have passed school reform legislation&quest; At what aspects of public education is this reform legislation aimed&quest; Are there significant variations across states in such reform legislation&quest; What has contributed most to the passage of such legislation&quest; Is it the socioeconomic characteristics of individual states or the structural and procedural characteristics of their legislative branch that better explain school reform legislation&quest; Analysis of data from the 50 states reveals greater variation in legislative results that reform public schools. The regional locus of most reform was the south. Most importantly, school reform legislation was found to be influenced by the interaction of a multitude of divergent forces. This finding suggests that researchers interested in the determinants of legislative action must move beyond analysis of whether economic or political forces shape legislative outcomes to inquire how economic, political and other forces interact when a given reform effort reaches the legislative halls of the states. Copyright 1988 by The Policy Studies Organization.