J Med Assoc Thai. 2006 Oct;89(10):1753-5.Primary umbilical endometriosis.Techapongsatorn S, Techapongsatorn S.Department of Surgery, Bangkok Metropolitan Administration Medical College and Vajira Hospital, Bangkok 10300, Thailand.A 45-year old nulliparous woman presented with umbilical pigmented lesion with cyclical bleeding. The lesion was excised and pathological diagnosis was umbilical endometriosis. The authors reviewed the current literature and discussed the different diagnosis and management of umbilical endometriosis.PMID: 17128853 [PubMed – in process] ________________________________________ Ann Pathol. 2006 Sep;26(4):293-4. [A woman with an unusual bladder tumor][Article in French]Bolli S, Abdou M, Fournier D, Defabiani N, Girardet C.Service d’Histocytopathologie, ICHV, Avenue Gd-Champsec 86, CP 736, 1951 Sion, Suisse.Publication Types: ? Case ReportsPMID: 17128162 [PubMed – indexed for MEDLINE] ________________________________________ Fertil Steril. 2007 Mar;87(3):485-9. Epub 2006 Nov 27. Clinical evaluation of endometriosis and differential response to surgical therapy with and without application of Oxiplex/AP* adhesion barrier gel.diZerega GS, Coad J, Donnez J.Livingston Reproductive Biology Laboratories, Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. dizerega@usc.eduOBJECTIVE: To correlate parameters of endometriosis obtained during routine clinical evaluation with the subsequent formation of adhesions following surgical treatment by laparoscopy. DESIGN: Randomized, controlled, double-blind, clinical trial. SETTING: Tertiary referral centers for the treatment of endometriosis. PATIENT(S): Thirty-seven patients (65 with adnexa) with stage I-III endometriosis; endometrioma-only patients were excluded. INTERVENTION: Laparoscopic surgical treatment of endometriosis, followed by randomization to Oxiplex/AP (FzioMed, Inc., San Luis Obispo, California) gel treatment (treated group) of adnexa, or surgery alone (control group); follow-up laparoscopy 6-10 weeks later. MAIN OUTCOME MEASURE(S): Adnexal Americn Fertility Society score, correlated with color and location of endometriosis, as well as stage of disease determined by masked review of videotapes. RESULT(S): Control patients with at least 50% red lesions had a greater increase in ipsilateral adnexal adhesion scores than patients with mostly black or white and/or clear lesions. Treated patients with red lesions had a greater decrease in adnexal adhesion scores than control patients. There was a correlation between baseline endometriosis stage and postoperative adhesion formation in control patients, but not treated patients. CONCLUSION(S): Patients with red endometriotic lesions had greater increases in their adhesion scores than patients with only black, white, and/or clear lesions. Oxiplex/AP gel was effective in reducing adhesions, compared to surgery alone, in all groups.Publication Types: ? Randomized Controlled Trial ? Research Support, Non-U.S. Gov’t PMID: 17126335 [PubMed – indexed for MEDLINE] ________________________________________ Pharmacotherapy. 2006 Dec;26(12):1811-5. Recurrent anaphylaxis associated with gonadotropin-releasing hormone analogs: case report and review of the literature.Lam C, Tjon J, Hamilton J, Ahmet AH.Department of General Paediatrics, University of Toronto, Toronto, Ontario, Canada.An 8-year-old girl with idiopathic central precocious puberty experienced multiple episodes of anaphylaxis after receiving a goserelin acetate implant. She was hospitalized and treated with epinephrine, antihistamine, and corticosteroids. The goserelin implant was surgically excised; however, anaphylactic symptoms continued for 4 days after excision. Less severe systemic symptoms recurred 6 weeks after removal; these were possibly due to leakage of the depot drug into subcutaneous tissues. It was noted that 3 years earlier, the patient had developed a similar, milder systemic allergic reaction to leuprolide acetate that required treatment with oral prednisone and antihistamines. Intradermal testing yielded positive results for leuprolide. Gonadotropin-releasing hormone (GnRH) analogs, including leuprolide acetate and goserelin acetate, are commonly prescribed for patients with prostatic carcinoma, endometriosis, and precocious puberty. A literature review identified a single case report of a systemic hypersensitivity reaction involving goserelin acetate and several reports of systemic hypersensitivity reactions associated with leuprolide acetate. We found no reports of systemic reactions to GnRH analogs in pediatric patients. Clinicians should be aware of the potential association of GnRH analogs with systemic reactions. They should also recognize that recurrent anaphylaxis may occur due to the long half-life of these therapeutic agents in tissue.Publication Types: ? Case ReportsPMID: 17125443 [PubMed – indexed for MEDLINE] ________________________________________ Proteomics. 2007 Jan;7(1):130-42. An investigation of the effects of endometriosis on the proteome of human eutopic endometrium: a heterogeneous tissue with a complex disease.Fowler PA, Tattum J, Bhattacharya S, Klonisch T, Hombach-Klonisch S, Gazvani R, Lea RG, Miller I, Simpson WG, Cash P.Department of Obstetrics & Gynaecology, University of Aberdeen, Aberdeen, UK. p.a.fowler@abdn.ac.ukThe pathogenesis of endometriosis includes the proliferation of heterogeneous endometrial cells and their invasion into ectopic sites within the peritoneal cavity. This may be due to abnormalities of the eutopic endometrium itself, predisposing the cells to survive and implant ectopically. We investigated the applicability of 2-DE gels and peptide mass mapping to identify candidate endometrial proteins with a role in endometriosis. Despite the heterogeneous nature of endometrium, our results show that combining the analysis of 2-DE gels and peptide mass mapping yields consistent data. We identified dysregulated proteins in women with endometriosis which included: (i) molecular chaperones including heat shock protein 90 and annexin A2, (ii) proteins involved in cellular redox state, such as peroxiredoxin 2, (iii) proteins involved in protein and DNA formation/breakdown, including ribonucleoside-diphosphate reductase, prohibitin and prolyl 4-hydroxylase, and (iv) secreted proteins, such as apolipoprotein A1. These proteins have functions which suggest that they could play a role in the pathogenesis of endometriosis. This study demonstrated that 2-DE gel analysis and mass spectroscopic protein identification are suitable for the identification of proteins with candidate associations with endometriosis. These techniques should be used on a larger scale to identify endometriosis-related proteins, thus improving the understanding of this complex disease.Publication Types: ? Research Support, Non-U.S. Gov’tPMID: 17124717 [PubMed – indexed for MEDLINE] ________________________________________ Fertil Steril. 2007 Mar;87(3):619-26. Epub 2006 Nov 21. Possible role of the plasminogen activation system in human subfertility.Ebisch IM, Steegers-Theunissen RP, Sweep FC, Zielhuis GA, Geurts-Moespot A, Thomas CM.Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.OBJECTIVE: To correlate components of the plasminogen activator (PA) system with fertility outcome parameters in participants in an IVF/intracytoplasmic sperm injection (ICSI) procedure. DESIGN: Case-control study. SETTING: Outpatient clinic for IVF/ICSI treatment at the Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. PATIENT(S): One hundred and fifty-six couples undergoing an IVF/ICSI procedure. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), and t-PA-PAI-1 complex concentrations in the ejaculate, spermatozoa, and follicular fluid (FF). RESULT(S): Concentrations of t-PA were higher in spermatozoa of the male factor subfertility group (geometrical mean, 77.1 pg/million spermatozoa; 25th-75th percentiles, 31.8-211.2), compared to fertile men (geometrical mean, 1.91; 25th-75th percentiles, 0.74-5.79) and idiopathic subfertile men (geometrical mean, 3.14; 25th-75th percentiles, 0.97-9.97). Furthermore, the concentration of t-PA in spermatozoa was significantly associated with pregnancy (odds ratio [OR], 0.995). Likewise, a trend was shown for higher t-PA concentrations in the FF of women with fallopian-tube pathology (geometrical mean, 18.5 pg t-PA/mg protein; 25th-75th percentiles, 11.4-25.7) or endometriosis (geometrical mean, 18.8; 25th-75th percentiles, 11.4-27.1), compared to fertile women (geometrical mean, 14.3; 25th-75th percentiles, 10.3-17.6) and idiopathic subfertile women (geometrical mean, 13.9; 25th-75th percentiles, 9.5-17.8). Also, t-PA in FF is associated with the proportion of cleaved embryos (regression coefficient, 0.16). The concentrations of u-PA, PAI-1, and t-PA-PAI-1 complex were comparable between diagnostic subgroups in both men and women. CONCLUSION(S): The t-PA concentrations in spermatozoa and FF tend to be higher in human subfertility, and seem to be associated with some fertility outcome parameters.PMID: 17123524 [PubMed – indexed for MEDLINE] ________________________________________ Mol Hum Reprod. 2007 Feb;13(2):117-22. Epub 2006 Nov 22. Estrogen receptor alpha-351 XbaI*G and -397 PvuII*C-related genotypes and alleles are associated with higher susceptibilities of endometriosis and leiomyoma.Hsieh YY, Wang YK, Chang CC, Lin CS.Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung and Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.Endometriosis and leiomyoma are both common estrogen-related gynaecological diseases. We aimed to elucidate the association of estrogen receptor alpha (ERalpha)-351 A>G (XbaI) and -397 T>C (PvuII) gene polymorphisms with endometriosis and leiomyoma. Women were divided into three groups: (i) severe endometriosis (n = 112), (ii) leiomyoma (n = 106) and (iii) normal controls (n = 110). Genomic DNA was obtained from peripheral leukocytes. ERalpha-351 A/G XbaI and -397 T/C PvuII polymorphisms were assayed by the method of PCR and restriction fragment length polymorphism (RFLP). Genotypes and allelic frequencies in each group were compared. The genotype/allele frequencies of ERalpha-351 and -397 polymorphisms in endometriosis or leiomyoma groups were different from those of normal controls. ERalpha mutant-related genotypes/alleles (-351G and -397C) presented higher percentages in the endometriosis/leiomyoma population compared with normal controls. Proportions of ERalpha-351 AA/AG/GG genotypes and A/G alleles in each group were (i) 26.8/57.1/16.1 and 55.4/44.6%; (ii) 19.8/52.8/27.4 and 46.2/53.8% and (iii) 33.6/64.6/1.8 and 65.9/34.1%. Proportions of ERalpha-397 TT/TC/CC genotypes and T/C alleles in each group were (i) 24.1/60.7/15.2 and 54.5/45.5%; (ii) 23.6/70.8/5.6 and 59/41% and (iii) 54.5/40/5.5 and 74.5/25.5%. We concluded that ERalpha-351 XbaI*G- and -397 PvuII*C-related genotypes/alleles were correlated with higher susceptibilities of endometriosis or leiomyoma, which might be associated with related pathogeneses.PMID: 17121748 [PubMed – in process] ________________________________________ Eur Radiol. 2006 Nov 22; [Epub ahead of print] Cine MR imaging of uterine peristalsis in patients with endometriosis.Kido A, Togashi K, Nishino M, Miyake K, Koyama T, Fujimoto R, Iwasaku K, Fujii S, Hayakawa K.Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan, akikido@kuhp.kyoto-u.ac.jp.Endometriosis is one of the most important causes of infertility; however the precise mechanism by which it affects female fertility is unclear. The objective of this study was to study the functional aspects of the uterus by evaluating uterine contractility in patients with endometrial cysts of the ovary. The study population was recruited from two institutes and consisted of 26 women (periovulatory (10), luteal (13), and menstrual phase (3); age range: 19-51 years) with untreated endometriosis; the control group consisted of 12 healthy women (age range: 22-41 years). Cine MR imaging obtained by a 1.5T magnet was visually evaluated at 12x faster than real speed, focusing on the presence of uterine peristalsis, the direction and frequency of peristalsis, and the presence of sustained uterine contractions. Uterine peristalsis was identifiable in 3/10, 3/13, and 3/3 of the endometriosis patients in each menstrual cycle, respectively, and in 11/12, 3/12, and 5/12 of their control subjects. Peristaltic detection rate and frequency were significantly less for the endometriosis group than for the controls in the periovulatory phase only (p<0.05). Sustained contractions were recognized in 19/36 control subjects and in 13/26 endometriosis patients, but the difference was not significant. Uterine peristalsis appears to be suppressed during the periovulatory phase in patients with endometriosis, which may have an adverse effect on sperm transport.PMID: 17119973 [PubMed – as supplied by publisher] ________________________________________ Hernia. 2006 Nov 22; [Epub ahead of print]Endometriosis mimicking hernia recurrence.Ducarme G, Uzan M, Poncelet C.Department of Obstetrics and Gynecology, Assistance Publique – Hopitaux de Paris, CHU Jean Verdier, Avenue du 14 Juillet, 93140, Bondy, France, g.ducarme@gmail.com.Endometriosis is a common gynecologic condition and has been described in several locations, mostly in the pelvis. Extragenital endometriosis may appear as a painful nodule evoking an inguinal hernia. Scar endometriosis after inguinal hernia repair seems to be a rare occurrence. We report an unusual case of a 28-year-old woman who developed a scar endometriosis 2 years after an inguinal hernia repair. This case highlights that the presence of a painless inguinal mass similar to a recurrent hernia, with possible swelling related to the menstrual cycle, may evoke endometriosis, especially after a previous hernia repair and should lead to prompt diagnosis, wide excision, and gynecological advice.PMID: 17119856 [PubMed – as supplied by publisher] ________________________________________ Rheumatology (Oxford). 2006 Dec;45(12):1533. Chronic shoulder pain and diaphragmatic endometriosis.Freeston JE, Green MJ, King DG, Iveson JM.Academic Unit of Musculoskeletal Disease, Chapel Allesten Hospital, Leeds, UK. medjef@leeds.ac.ukPublication Types: ? Case ReportsPMID: 17118940 [PubMed – indexed for MEDLINE] ________________________________________ Fertil Steril. 2007 Mar;87(3):698-701. Epub 2006 Nov 21. Effect of the immunomodulator leflunomide on the induction of endometriosis in an experimental rat model.Aytan H, Caglar P, Uygur D, Zergeroglu S, Batioglu S.The effect of immunomodulator leflunomide on the development of an experimental endometriosis model was assessed by surgically transplanting autologous fragments of endometrial tissue onto the inner surface of the abdominal wall and arterial cascades of the small intestines. Leflunomide was found to affect the development of endometriosis negatively and seemed to interfere with the growth and maintenance of the uterine explant in this experimental rat model.Publication Types: ? LetterPMID: 17118364 [PubMed – indexed for MEDLINE] ________________________________________ Reprod Biol Endocrinol. 2006 Oct 9;4 Suppl 1:S9 [Epub ahead of print] Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women.Lessey BA, Palomino WA, Apparao K, Young SL, Lininger RA.Division of Reproductive Endocrinology and Infertility, University Medical Group, Department of Obstetrics and Gynecology, Greenville Hospital System, Greenville, SC, USA. blessey@ghs.org.ABSTRACT : Endometriosis is a disorder that affects 5% of the normal population but is present in up to 40% of women with pelvic pain and/or infertility. Recent evidence suggests that the endometrium of women with endometriosis exhibits progesterone insensitivity. One endometrial protein that fluctuates in response to progesterone is the estrogen receptor-alpha (ER alpha), being down-regulated at the time of peak progesterone secretion during the window of implantation. Here we demonstrate that the biomarker of uterine receptivity, beta 3 integrin subunit, is reduced or absent in some women with endometriosis and that such defects are accompanied by inappropriate over-expression of ER alpha during the mid-secretory phase. Using a well-differentiated endometrial cell line we showed that the beta 3 integrin protein is negatively regulated by estrogen and positively regulated by epidermal growth factor (EGF). By competing against estrogen with various selective estrogen receptor modulators (SERMs) and estrogen receptor agonists and antagonists, inhibition of expression of the beta 3 integrin by estrogen can be mitigated. In conclusion, we hypothesize that certain types of uterine receptivity defects may be caused by the loss of appropriate ER alpha down-regulation in the mid-secretory phase, leading to defects in uterine receptivity. Such changes might be effectively treated by timely administration of the appropriate anti-estrogens to artificially block ER alpha and restore normal patterns of gene expression. Such treatments will require further clinical studies.PMID: 17118173 [PubMed – as supplied by publisher] ________________________________________ Reprod Biol Endocrinol. 2006 Oct 9;4 Suppl 1:S8 [Epub ahead of print] Role of nonhuman primate models in the discovery and clinical development of selective progesterone receptor modulators (SPRMs).Chwalisz K, Garg R, Brenner R, Slayden O, Winkel C, Elger W.TAP Pharmaceutical Products Inc, Lake Forest, Illinois, USA. Kristof.Chwalisz@TAP.com.ABSTRACT : Selective progesterone receptor modulators (SPRMs) represent a new class of progesterone receptor ligands that exert clinically relevant tissue-selective progesterone agonist, antagonist, partial, or mixed agonist/antagonist effects on various progesterone target tissues in an in vivo situation depending on the biological action studied. The SPRM asoprisnil is being studied in women with symptomatic uterine leiomyomata and endometriosis. Asoprisnil shows a high degree of uterine selectivity as compared to effects on ovulation or ovarian hormone secretion in humans. It induces amenorrhea and decreases leiomyoma volume in a dose-dependent manner in the presence of follicular phase estrogen concentrations. It also has endometrial antiproliferative effects. In pregnant animals, the myometrial, i.e. labor-inducing, effects of asoprisnil are blunted or absent. Studies in non-human primates played a key role during the preclinical development of selective progesterone receptor modulators. These studies provided the first evidence of uterus-selective effects of asoprisnil and structurally related compounds, and the rationale for clinical development of asoprisnil.PMID: 17118172 [PubMed – as supplied by publisher] ________________________________________ Reprod Biol Endocrinol. 2006 Oct 9;4 Suppl 1:S7 [Epub ahead of print] A baboon model for endometriosis: implications for fertility.Hastings JM, Fazleabas AT.Department of Obstetrics and Gynecology (MC808), College of Medicine, University of Illinois at Chicago, 820 S Wood Street, Chicago, Illinois, 60612, USA. julieh@uic.edu.ABSTRACT : Endometriosis is one of the most common causes of chronic pelvic pain and infertility in women in the reproductive age group. Although the existence of this disease has been known for over 100 years our current knowledge of its pathogenesis and the pathophysiology of its related infertility remains unclear. Several reasons contribute to our lack of knowledge, the most critical being the difficulty in carrying out objective long-term studies in women. Thus, we and others have developed a model of this disease in the non-human primate, the baboon (Papio anubis). Intraperitoneal inoculation of autologous menstrual endometrium results in the development of endometriotic lesions with gross morphological characteristics similar to those seen in the human. Multiple factors have been implicated in endometriosis-associated infertility. We have described aberrant levels of factors involved in multiple pathways important in the establishment of pregnancy, in the endometrium of baboons induced with endometriosis. Specifically, we have observed dysregulation of proteins involved in invasion, angiogenesis, methylation, cell growth, immunomodulation, and steroid hormone action. These data suggest that, in an induced model of endometriosis in the baboon, an increased angiogenic capacity, decreased apoptotic potential, progesterone resistance, estrogen hyper-responsiveness, and an inability to respond appropriately to embryonic signals contribute to the reduced fecundity associated with this disease.PMID: 17118171 [PubMed – as supplied by publisher] ________________________________________ Reprod Biol Endocrinol. 2006 Oct 9;4 Suppl 1:S5 [Epub ahead of print] Regulation of human endometrial function: mechanisms relevant to uterine bleeding.Critchley HO, Kelly RW, Baird DT, Brenner RM.Department of Reproductive and Developmental Sciences, University of Edinburgh, Centre for Reproductive Biology, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. hilary.critchley@ed.ac.uk.ABSTRACT : This review focuses on the complex events that occur in the endometrium after progesterone is withdrawn (or blocked) and menstrual bleeding ensues. A detailed understanding of these local mechanisms will enhance our knowledge of disturbed endometrial/uterine function – including problems with excessively heavy menstrual bleeding, endometriosis and breakthrough bleeding with progestin only contraception. The development of novel strategies to manage these clinically significant problems depends on such new understanding as does the development of new contraceptives which avoid the endometrial side effect of breakthrough bleeding.PMID: 17118169 [PubMed – as supplied by publisher] ________________________________________ Tech Coloproctol. 2006 Dec;10(4):350-2. Epub 2006 Nov 27. Laparoscopic combined rectal anterior resection and total hysterectomy with bilateral salpingo-oophorectomy.Lakshman N, Chang R, Ho Y.Department of Surgery, School of Medicine James Cook University, Townsville, QLD, Australia.Pelvic conditions involving both the colorectum and gynaecological organs are traditionally treated by laparotomy. We report two cases of colorectal cancer and one of endometriosis treated by laparoscopic anterior resection and total hysterectomy bilateral salpingooophorectomy (LapAR & THBSO), at the same session. There have been no previously reported cases of the feasibility of such combined procedures, safely performed. Our results confirm that LapAR & THBSO is feasible and offers the advantages of a laparoscopic procedure in the hands of a well trained laparoscopic colorectal surgeon and gynaecologist working together.Publication Types: ? Case ReportsPMID: 17115309 [PubMed – indexed for MEDLINE] ________________________________________ Tech Coloproctol. 2006 Dec;10(4):357-60. Epub 2006 Nov 27. Endoanal ultrasonography in the diagnosis and operative management of perianal endometriosis: report of two cases.Toyonaga T, Matsushima M, Tanaka Y, Nozawa M, Sogawa N, Kanyama H, Tanaka M.Coloproctology Center, Department of Surgery Matsushima Hospital, Nishi-ku, Yokohama, Japan. toyozo7@yahoo.co.jpWe report two cases of perianal endometriosis in which we were greatly assisted by endoanal ultrasonography. Patient 1 was a 43-year-old woman with perianal pain. Endosonography showed a hypoechoic mass in the anterior perianal region without involvement of the anal sphincter. Local excision was performed under spinal anesthesia without damage to the anal sphincter. Patient 2 was a 30-year-old woman with perianal pain coinciding with her menstrual period. Endosonography showed a heterogeneous mass containing cystic anechoic areas in the right anterior perianal region and involving the external anal sphincter. Wide excision, including the episiotomy scar and part of the external anal sphincter, and primary sphincteroplasty were performed under spinal anesthesia. According to our experience, preoperative endosonography is a reliable technique for visualizing perianal endometriosis and for diagnosing anal sphincter involvement. Operative management should be determined on the basis of preoperative and intraoperative ultrasonographic assessment.Publication Types: ? Case ReportsPMID: 17115307 [PubMed – indexed for MEDLINE] ________________________________________ Int Urol Nephrol. 2006;38(3-4):469-71. Epub 2006 Nov 18. Surgical management of bilateral ureteral endometriosis.Yee DS, Shanberg AM, Ngo AT, Baghdassarian R.Department of Urology, University of California, Irvine School of Medicine, 101 The City Drive, Bldg 26, Rm 24, Route 81, Orange, CA, 92868, USA, dyee@uci.edu.Ureteral endometriosis is a rare disease that typically is unilateral. Endometriosis involving both ureters and surgical management after hormone therapy failure has seldom been described. We describe a patient with bilateral ureteral endometriosis who underwent ureteroneocystostomy with psoas hitches of both ureters. A 33-year-old woman with advanced endometriosis and recurrent pyelonephritis was found to have high-grade bilateral ureteral obstruction at the pelvic inlet from ureteral endometriosis. The patient subsequently underwent a supracervical hysterectomy with bilateral salpingo-oophorectomy, ureterolysis, and ureteroneocystostomy with psoas hitches and ureteral stent placements. Surgical therapy is reserved for advanced disease with the optimal choice being a ureteral reimplantation with a psoas hitch. The key operative point for a successful psoas hitch ureteral reimplantation is completely mobilizing the bladder anteriorly and laterally.PMID: 17115290 [PubMed – in process] ________________________________________ Toxicol Lett. 2006 Dec 15;167(3):238-44. Epub 2006 Oct 24. Serum dioxin-like compounds and aromatase (CYP19) expression in endometriotic tissues.Heilier JF, Donnez J, Defrere S, Van Kerckhove V, Donnez O, Lison D.Universite catholique de Louvain, Faculty of Medicine, Industrial Toxicology and Occupational Medicine Unit, 53.02 Avenue E. Mounier, B-1200 Brussels, Belgium. Jean-Francois.Heilier@uclouvain.beDioxin-like compounds (DLCs) are suspected etiological factors of endometriosis but their potential mechanisms of action remain elusive. Because endometriosis is an estrogen-dependent disease and since aromatase (CYP19), a key enzyme in estrogen biosynthesis, was recently demonstrated to be expressed in endometriotic lesions, we hypothesized that dioxin-like compounds could modulate local estrogen production through an up-regulation of aromatase. We tested this hypothesis by examining the correlation between serum DLC levels and CYP19 expression in endometriotic tissue obtained from 47 patients with peritoneal, ovarian endometriosis and/or deep endometriotic nodules of the rectovaginal septum. Aromatase expression was assessed by real-time RT-PCR in biopsied endometriotic tissues [peritoneal (n=19), ovarian (n=17) endometriosis and deep endometriotic nodules of the recto-vaginal septum (n=29)]. The relationship between aromatase expression and DLCs was traced by simple regression analysis. DLCs did not appear to be significant determinants of aromatase expression. CYP1A1 expression, measured as a positive control, was found associated with current smoking but not with DLCs. We conclude that DLCs do probably not facilitate the growth of endometriotic lesions by up-regulating the local expression of aromatase.Publication Types: ? Research Support, Non-U.S. Gov’tPMID: 17112691 [PubMed – indexed for MEDLINE] ________________________________________ Am J Epidemiol. 2007 Feb 1;165(3):325-33. Epub 2006 Nov 16. Receiver operating characteristic curve inference from a sample with a limit of detection.Perkins NJ, Schisterman EF, Vexler A.Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.The receiver operating characteristic curve is a commonly used tool for evaluating biomarker usefulness in clinical diagnosis of disease. Frequently, biomarkers being assessed have immeasurable or unreportable samples below some limit of detection. Ignoring observations below the limit of detection leads to negatively biased estimates of the area under the curve. Several correction methods are suggested in the areas of mean estimation and testing but nothing regarding the receiver operating characteristic curve or its summary measures. In this paper, the authors show that replacement values below the limit of detection, including those suggested, result in the same biased area under the curve when properly accounted for, but they also provide guidance on the usefulness of these values in limited situations. The authors demonstrate maximum likelihood techniques leading to asymptotically unbiased estimators of the area under the curve for both normally and gamma distributed biomarker levels. Confidence intervals are proposed, the coverage probability of which is scrutinized by simulation study. An example using polychlorinated biphenyl levels to classify women with and without endometriosis illustrates the potential benefits of these methods.Publication Types: ? Research Support, N.I.H., IntramuralPMID: 17110640 [PubMed – indexed for MEDLINE]

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