Androgen receptor expression in human ovarian and uterine tissue of long term androgen-treated transsexual women

Androgen receptor (AR) modulation in human uteri and ovaries of long term androgen-treated transsexual female patients was investigated. Androgen receptor expression was evaluated immunohistochemically in the ovaries of 11 and the endometria and myometria of six androgen-treated transsexual female patients. This was compared with AR expression in the ovaries and uteri of premenopausal and postmenopausal women not receiving treatment and in 10 ovaries of female patients with polycystic ovarian disease (PCOD). In the normal ovaries germinal epithelium, granulosa cells of antral follicles, corpus luteum, and thecal and stromal cells exhibited moderate AR expression. The more intense and uniform staining of ovarian stroma of female transsexual patients and those of patients with PCOD compared with ovarian stroma of normal controls was most remarkable. This similarity in histology and distribution of ARs supports the hypothesis that PCOD is an androgen-mediated disorder. Immunostaining for ARs was only occasionally detectable in the uteri of premenopausal and postmenopausal women. In contrast, myometrial and endometrial stroma of the uteri of female transsexual patients displayed an intense and diffuse nuclear immunostaining, but glandular epithelia remained unstained. Western blot analysis of the ovaries and uterine myometrial tissue samples from transsexual female patients confirmed the presence of the 110-kd AR molecule. Because the androgen treatment of some transsexual female patients was discontinued 6 weeks before they underwent hysterosalpingo-oophorectomy, our data indicate a stable and persistent androgen-induced up-regulation of AR expression in ovaries

The occurrence of diversion colitis in patients with a sigmoid neovagina

Diversion colitis is an inflammatory process occurring in segments of the colorectum surgically diverted from the fecal stream. Clinical symptoms of this condition are rectal discomfort, pain, discharge, and bleeding. We diverted isolated segments of sigmoid to create neovaginas in patients with aplasia vaginae and in male to female transsexuals. In contrast to what is reported in most studies of diversion colitis, the neovagina consists of an isolated segment not connected to the anus in patients without any pre-existing bowel disease. To investigate the occurrence of diversion colitis in these sigmoid-neovaginas we studied biopsy specimens from 13 patients. Most of the patients complained of discharge and slight blood loss from their sigmoid-neovagina. Microscopic examination of the biopsy specimens showed lymphocytic infiltration in all cases. Four cases showed an acute inflammatory infiltrate in the lamina propria. Our results indicate that the changes observed on clinical and histopathologic examinations represent the entity of mild diversion colitis. We conclude that diversion colitis also occurs in a sigmoid neovagina

The low transverse Pfannenstiel incision and the prevalence of incisional hernia and nerve entrapment

Objective: The authors determined the prevalence of incisional hernia and nerve entrapment in patients with a low transverse Pfannenstiel incision. Summary Background Data: The literature on the Pfannenstiel incision suggests an incisional hernia rate of 0.0% to 0.5%. However, in these series, physical examination, which is essential in the authors' view, was not performed. To the authors' knowledge, the prevalence of nerve entrapment after the Pfannenstiel incision is not known or has never been published. Methods: All adult women, operated on between 1986 and 1992 using a Pfannenstiel incision and not having had another lower abdominal incision other than for laparoscopy, were invited for follow-up at the outpatient department. All patients were interviewed and subjected to a physical examination, with special interest to the presence of incisional hernia or nerve entrapment. Results: In patients having had a Pfannenstiel incision, no incisional hernias were found. In patients also having had a laparoscopy, the incisional hernia rate was 3.5%. Nerve entrapment was found in 3.7%. The length of the incision was ide

Gene expression profiles of human endometrial cancer samples using a cDNA-expression array technique: assessment of an analysis method

The recently developed cDNA expression array technique can be used to generate gene-expression fingerprints of tumour specimens. To gain insight into molecular mechanisms involved in the development and progression of cancer, this cDNA expression array technique could be a useful tool, however, no established methods for interpreting the results are yet available. We used the Atlas cancer cDNA expression array (Clontech, USA) for analysing total RNA isolated from four human endometrial carcinoma samples (two cell-lines and two tissue samples), one benign endometrial tissue sample and a human breast cancer cell-line, in order to develop a method for analysing the array data. The obtained gene-expression profiles were highly reproducible. XY-scatterplots and regression analysis of the logarithmic transformed data provided a practical method to analyse the data without the need of preceding normalization. Three genes (Decorin, TIMP3 and Cyclin D1) were identified to be differentially expressed between the benign endometrial tissue sample and the endometrial carcinoma samples (tissue and cell-lines). These three genes may potentially be involved in cancer progression. A higher degree of similarity in gene-expression profile was found between the endometrial samples (tissue and cell-lines) than between the endometrial samples and the breast cancer cell-line, which is indicative for an endometrial tissue-specific gene-expression profile. © 2000 Cancer Research Campaig

Consequences of loss of progesterone receptor expression in development of invasive endometrial cancer

PURPOSE: In endometrial cancer, loss of progesterone receptors (PR) is associated with more advanced disease. This study aimed to investigate the mechanism of action of progesterone and the loss of its receptors (PRA and PRB) in development of endometrial cancer. EXPERIMENTAL DESIGN: A 9600-cDNA microarray analysis was performed to study regulation of gene expression in the human endometrial cancer subcell line Ishikawa PRAB-36 by the progestagen medroxy progesterone acetate (MPA). Five MPA-regulated genes were selected for additional investigation. Expression of these genes was studied by Northern blot and by immunohistochemistry in Ishikawa subcell lines expressing different PR isoforms. Additionally, endometrial cancer tissue samples were immunohistochemically stained to study the in vivo protein expression of the selected genes. RESULTS: In the PRAB-36 cell line, MPA was found to regulate the expression of a number of invasion- and metastasis-related genes. On additional investigation of five of these genes (CD44, CSPG/Versican, Tenascin-C, Fibronectin-1, and Integrin-beta 1), it was observed that expression and progesterone regulation of expression of these genes varied in subcell lines expressing different PR isoforms. Furthermore, in advanced endometrial cancer, it was shown that loss of expression of both PR and E-cadherin was associated with increased expression CD44 and CSPG/Versican. CONCLUSION: The present study shows that progestagens exert a modulatory effect on the expression of genes involved in tumor cell invasion. As a consequence, loss of PR expression in human endometrial cancer may lead to development of a more invasive phenotype of the respective tumor

Development of a patient decision aid for patients with breast cancer who consider immediate breast reconstruction after mastectomy

Purpose The aim of this study was to develop a patient decision aid (pDA) that could support patients with breast cancer (BC) in making an informed decision about breast reconstruction (BR) after mastectomy. Methods The development included four stages: (i) Establishment of a multidisciplinary team; (ii) Needs assessment consisting of semi-structured interviews in patients and a survey among healthcare professionals (HCPs); (iii) Creation of content, design and technical system; and (iv) Acceptability and usability testing using a think-aloud approach in patients and interviews among HCPs and representatives of the Dutch Breast Cancer Patient Organization. Results From the needs assessment, three themes were identified: Challenging period to make a decision, Diverse motivations for a personal decision and Information needed to make a decision about BR. HCPs valued the development of a pDA, especially to prepare patients for consultation. The pDA that was developed contained three parts: first, a consultation sheet for oncological breast surgeons to introduce the choice; second, an online tool including an overview of reconstructive options, the pros and cons of each option, information on the consequences of each option for daily life, exercises to clarify personal values and patient stories; and third, a summary sheet with patients' values, preferences and questions to help inform and guide the discussion between the patient and her plastic surgeon. The pDA was perceived to be informative, helpful and easy to use by patients and HCPs. Conclusion Consistent with information needs, a pDA was developed to support patients with BC who consider immediate BR in making an informed decision together with their plastic surgeon. Patient or Public Contribution Patients participated in the needs assessment and in acceptability and usability testing.Hereditary cancer genetic

Enhanced port-wine stain lightening achieved with combined treatment of selective photothermolysis and imiquimod

BACKGROUND: Pulsed dye laser is the gold standard for treatment of port wine stain birthmarks but multiple treatments are required and complete resolution is often not achieved. Post-treatment vessel recurrence is thought to be a factor that limits efficacy of pulsed dye laser treatment of port wine stains. Imiquimod 5% cream is an immunomodulator with anti-angiogenic effects. OBJECTIVE: To determine if application of imiquimod 5% cream after pulsed dye laser improves treatment outcome. METHODS: Healthy patients with port wine stains (n = 24) were treated with pulsed dye laser and then randomized to apply post-treatment placebo or imiquimod 5% cream for 8 weeks. Chromameter measurements (CIE L*a*b* colorspace) for 57 port wine stain sites (multiple sites per subject) were taken at baseline and compared with measurements taken 8 weeks post-treatment. The change in a* and ΔE were measured to quantify treatment outcome. RESULTS: Two subjects developed minor skin irritation. Other adverse effects weren't noted. Average Δa* was 0.43 for pulsed dye laser + placebo sites (n = 25) and 1.27 for pulsed dye laser + imiquimod sites (n = 32) (p value = 0.0294) indicating a greater reduction in erythema with imiquimod. Average ΔE was 2.59 for pulsed dye laser + placebo and 4.08 for pulsed dye laser + imiquimod (p value = 0.0363), again indicating a greater color improvement with imiquimod. LIMITATIONS: Effects were evaluated after a single treatment and duration of effect is unknown. CONCLUSION: Combined selective photothermolysis and anti-angiogenic therapy may enhance port wine stain treatment efficacy

[Oral contraceptives increase the chance of venous thrombosis in factor V Leiden mutation].,[Oral contraceptives increase the chance of venous thrombosis in factor V Leiden mutation]

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