Citations

Abstract Background The aim was to evaluate outcomes in patients with ulcerative colitis complicated by primary sclerosing cholangitis (PSC) who required ileal pouch–anal anastomosis (IPAA) and orthotopic liver transplantation (OLT). Methods A retrospective analysis was performed of 32 patients undergoing both IPAA and OLT between 1980 and 2006. Data were collected regarding demographics, indication for surgery, postoperative complications, and outcome of IPAA and OLT. Results Thirty-day mortality after either procedure was nil. The median preoperative Model for End-stage Liver Disease (MELD) score for the group with initial IPAA was 8 (range 6–20) and the postoperative score was 11 (range 6–19). At 1 and 10 years, 32 and 26 of the 32 liver grafts had survived, and 31 and 30 of the 32 pouches, respectively. Fourteen patients require daily medical therapy for chronic pouchitis. At a median follow-up of 3·6 (range 0·2–16·2) years after the second of two procedures, responding patients reported a median of 5·5 stools per day and 2 stools per night. Conclusion IPAA and OLT are feasible and safe in patients requiring both procedures for ulcerative colitis and PSC. Functional outcomes are stable over time, despite an increased risk of chronic pouchitis.

Abstract The estrogen receptors (ER) α and β are important ligand-mediated transcription factors known to play significant biological roles in numerous tissues including bone. Despite the high homology shared by these receptors, recent studies have suggested that their function is largely unique. Although these receptors have been studied in detail for more than a decade, little data exist concerning the mechanisms by which these two proteins regulate distinct sets of genes. Using the TGFβ-inducible early gene-1 (TIEG) as a model, we demonstrate that TIEG is rapidly induced in response to estrogen in osteoblasts by ERβ, but not ERα. We have identified the regulatory elements utilized by ERβ and have demonstrated that ERβ recruits steroid receptor coactivator (SRC)1 and SRC2 to this regulatory region. Additionally, deletion of the ERβ-activation function 1 (AF1) domain drastically decreases the estrogen induction of TIEG. Through the use of chimeric receptors, we have demonstrated that the AF1 domain of ERβ is responsible for recruiting SRC1 and SRC2 and inducing the expression of TIEG in osteoblasts. Finally, SRC1, but not SRC2, is essential for TIEG induction by ERβ. Overall, these data demonstrate that the estrogen induction of TIEG is ERβ specific and that the AF1 domain of ERβ confers this specificity. Finally, a novel and important role for ERβ’s AF1 is implicated in the recruitment of specific coactivators, suggesting that the AF1 may play a significant role in conferring the differences in regulation of gene expression by these two receptors.

Abstract To better define the relationship between vascular calcification and bone mass/structure, we assessed abdominal aortic calcification (AAC), BMD, and bone microstructure in an age-stratified, random sample of 693 Rochester, MN, residents. Participants underwent QCT of the spine and hip and high-resolution pQCT (HRpQCT) of the radius to define volumetric BMD (vBMD) and microstructural parameters. AAC was quantified with the Agatston scoring method. In men, AAC correlated with lower vertebral trabecular and femoral neck vBMD (p < 0.001), but not after age or multivariable (age, body mass index, smoking status) adjustment. Separation into <50 and ≥50 yr showed this pattern only in the older men. BV/TV and Tb.Th inversely correlated with AAC in all men (p < 0.001), and Tb.Th remained significantly correlated after age adjustment (p < 0.05). Tb.N positively correlated with AAC in younger men (p < 0.001) but negatively correlated in older men (p < 0.001). The opposite was true with Tb.Sp (p = 0.01 and p < 0.001, respectively). Lower Tb.N and higher Tb.Sp correlated with AAC in older men even after multivariable adjustment. Among all women and postmenopausal women, AAC correlated with lower vertebral and femoral neck vBMD (p < 0.001) but not after adjustment. Lower BV/TV and Tb.Th correlated with AAC (p = 0.03 and p = 0.04, respectively) in women, but not after adjustment. Our findings support an age-dependent association between AAC and vBMD. We also found that AAC correlates with specific bone microstructural parameters in older men, suggesting a possible common pathogenesis for vascular calcification and deterioration in bone structure. However, sex-specific differences exist.

ABSTRACT Introduction The medical literature contains several definitions of premature ejaculation (PE). The most commonly quoted definition, the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision, and other definitions of PE are all authority based rather than evidence based, and have no support from controlled clinical and/or epidemiological studies. Aim The aim of this article is to develop a contemporary, evidence-based definition of PE. Methods In August 2007, the International Society for Sexual Medicine (ISSM) appointed several international experts in PE to an Ad Hoc Committee for the Definition of Premature Ejaculation. The committee met in Amsterdam in October 2007 to evaluate the strengths and weaknesses of current definitions of PE, to critique the evidence in support of the constructs of ejaculatory latency, ejaculatory control, sexual satisfaction, and personal/interpersonal distress, and to propose a new evidence-based definition of PE. Results The committee unanimously agreed that the constructs that are necessary to define PE are rapidity of ejaculation, perceived self-efficacy and control, and negative personal consequences from PE. The committee proposed that lifelong PE be defined as “. . . a male sexual dysfunction characterized by ejaculation which always or nearly always occurs prior to or within about one minute of vaginal penetration, and the inability to delay ejaculation on all or nearly all vaginal penetrations, and negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy.” This definition is limited to men with lifelong PE who engage in vaginal intercourse. The panel concluded that there are insufficient published objective data to propose an evidence-based definition of acquired PE. Conclusion The ISSM definition of lifelong PE represents the first evidence-based definition of PE. This definition will hopefully lead to the development of new tools and Patient Reported Outcome measures for diagnosing and assessing the efficacy of treatment interventions and encourage ongoing research into the true prevalence of this disorder and the efficacy of new pharmacological and psychological treatments.