Low temperature balloon battery, phase 2 Final report, 22 Apr. - 22 Nov. 1969

Low temperature rechargeable balloon batter

Vitamin D: Mechanism of action and biological effects in uterine fibroids

Uterine fibroids (UFs) are the most common benign gynecological tumors. It was esti-mated that fifty percent of women presenting with UFs has symptomatology that negatively in-fluences their quality of life. Pharmacological and/or surgical treatments are frequently required, depending on the woman’s desire to preserve fertility, with a high impact on healthcare costs. Generally, the use of currently available pharmacological treatments may lead to side effects. Therefore, there is a growing interest in a natural and safe approach for UFs. In recent years, epi-demiological studies reported a vitamin D deficiency in patients with UFs raised interest in the potential biological effects of vitamin D supplementation. In vitro studies proved vitamin D efficacy in inhibiting UFs growth by targeting pathways involved in the regulation of various biological processes, including proliferation, extracellular matrix (ECM) remodeling, DNA repair, signaling and apoptosis. However, clinical studies supported only in part the beneficial effects of vitamin D supplementation in reducing UFs growth and tumor volume. Randomized controlled trials and large population studies are mandatory as the potential clinical benefits are likely to be substantial

Molecular classification of selective oestrogen receptor modulators on the basis of gene expression profiles of breast cancer cells expressing oestrogen receptor α

The purpose of this study was to classify selective oestrogen receptor modulators based on gene expression profiles produced in breast cancer cells expressing either wtERα or mutant351ERα. In total, 54 microarray experiments were carried out by using a commercially available Atlas cDNA Expression Arrays (Clontech), containing 588 cancer-related genes. Nine sets of data were generated for each cell line following 24 h of treatment: expression data were obtained for cells treated with vehicle EtOH (Control); with 10−9 or 10−8 M oestradiol; with 10−6 M 4-hydroxytamoxifen; with 10−6 M raloxifene; with 10−6 M idoxifene, with 10−6 M EM 652, with 10−6 M GW 7604; with 5×10−5 M resveratrol and with 10−6 M ICI 182,780. We developed a new algorithm ‘Expression Signatures’ to classify compounds on the basis of differential gene expression profiles. We created dendrograms for each cell line, in which branches represent relationships between compounds. Additionally, clustering analysis was performed using different subsets of genes to assess the robustness of the analysis. In general, only small differences between gene expression profiles treated with compounds were observed with correlation coefficients ranged from 0.83 to 0.98. This observation may be explained by the use of the same cell context for treatments with compounds that essentially belong to the same class of drugs with oestrogen receptors related mechanisms. The most surprising observation was that ICI 182,780 clustered together with oestrodiol and raloxifene for cells expressing wtERα and clustered together with EM 652 for cells expressing mutant351ERα. These data provide a rationale for a more precise and elaborate study in which custom made oligonucleotide arrays can be used with comprehensive sets of genes known to have consensus and putative oestrogen response elements in their promoter regions

Laparoscopic Intracapsular Myomectomy in Women 40 Years Old and Over with Symptomatic Uterine Fibroids. A Pilot Study

Abstract Authors evaluated the impact of laparoscopic intracapsular myomectomy (LIM) in women 40 years of age and over with desire of future fertility compared with medical management of symptomatic fibroids, by a prospective cohort study in University affiliated Hospitals. This study includes a cohort of women 40 years of age and older with symptomatic intramural fibroids with desire of future fertility. Women with symptomatic fibroid uterus were offered to undergo LIM or medical management. They were encouraged to attempt conception either spontaneously or by assisted reproductive technology (ART) according to their individual preference. All women were followed for 2 years. Fibroid characteristics, pre- and post-surgical variables, including surgical complications, days of hospitalization, pregnancy rate, and obstetrical outcomes were collected. A total of 100 patient were included in the analysis. Fifty patients were assigned to the LIM group and 50 to the medical treatment group (MT). Groups were similar regarding age (43.5 ± 2.4 and 43.5 ± 2.4, p  = 0.99), body mass index (23.8 ± 3.1 and 24.2 ± 3.1, p  = 0.54), parity (0.46 ± 0.09 and 0.58 ± 0.09, p  = 0.37), fibroid number (1.38 ± 0.6 and 1.46 ± 0.6, p  = 0.53), and fibroid size (5.92 ± 1.62 cm vs. 5.94 ± 1.49 cm, p  = 0.949). Of the patients who underwent LIM, 62% conceived within the study period compared with 56% in the control group ( p  = 0.54). Pregnancy was achieved by ART in 44% of the patients of the LIM group and 30% in control group. There was no significant difference in pregnancy rates among the two groups regarding spontaneous pregnancy rate ( p  = 0.332), nor in pregnancies obtained by ART with own eggs ( p  = 0.146) and oocyte or embryo donation ( p  = 0.821). The take home baby rate was 65% (20/31) in the LIM group and 61% (17/28) in the control group ( p  = 0.7851). Both groups had similar rate of miscarriage ( p  = 0.748). Patients 40 years old and over with symptomatic fibroid uterus who undergo LIM have similar subsequent fertility and obstetrical outcomes than women treated with medical management. LIM has no detrimental impact on future fertility in women 40 years old and over

Comparative ultrastructure of collagen fibrils in uterine leiomyomas and normal myometrium

Objective: To examine the ultrastructural characteristics of extracellular matrix and mature collagen fibrils in uterine leiomyomas and compare them with those in adjacent normal myometrium. Design: Analysis of paired leiomyoma-myometrium in surgical specimens. Result(s): Observation of specimens at ϫ12,500 magnification indicated that collagen fibrils were more abundant, loosely packed, and arrayed in a nonparallel manner in leiomyomas compared with myometrium. Random areas were examined at ϫ6,500 to ϫ64,000 magnification and revealed collagen fibrils of equal diameter in both leiomyomas and myometrium. However, an ordered and regular barbed appearance was present in collagen fibrils from myometrium but was lacking in leiomyomas. Conclusion(s): Leiomyomas contain an abnormal collagen fibril structure and orientation, which suggests that the well-regulated fibril formation in myometrium is altered in leiomyomas. Alterations in collagen genes may play a role in the pathogenesis of leiomyomas. (Fertil Steril 2004;82(Suppl 3):118282(Suppl 3): -118

The Comparing Options for Management: PAtient-centered REsults for Uterine Fibroids (COMPARE-UF) registry: rationale and design

BACKGROUND: Uterine fibroids are common in premenopausal women, yet comparative effectiveness research on uterine fibroid treatments is rare. OBJECTIVE: The purpose of this study was to design and establish a uterine fibroid registry based in the United States to provide comparative effectiveness data regarding uterine fibroid treatment. STUDY DESIGN: We report here the design and initial recruitment for the Comparing Options for Management: Patient-centered REsults for Uterine Fibroids (COMPARE-UF) registry (Clinicaltrials.gov, NCT02260752), funded by the Agency for Healthcare Research and Quality in collaboration with the Patient-Centered Outcomes Research Institute. COMPARE-UF was designed to help answer critical questions about treatment options for women with symptomatic uterine fibroids. Women who undergo a procedure for uterine fibroids (hysterectomy, myomectomy [abdominal, hysteroscopic, vaginal, and laparoscopic/robotic], endometrial ablation, radiofrequency fibroid ablation, uterine artery embolization, magnetic resonance-guided focused ultrasound, or progestin-releasing intrauterine device insertion) at 1 of the COMPARE-UF sites are invited to participate in a prospective registry with 3 years follow up for postprocedural outcomes. Enrolled participants provide annual follow-up evaluation through an online portal or through traditional phone contact. A central data abstraction center provides information obtained from imaging, operative or procedural notes, and pathology reports. Women with uterine fibroids and other stakeholders are a key part of the COMPARE-UF registry and participate at all points from study design to dissemination of results. RESULTS: We built a network of 9 clinical sites across the United States with expertise in the care of women with uterine fibroids to capture geographic, racial, ethnic, and procedural diversity. Of the initial 2031 women who were enrolled in COMPARE-UF, 42% are self-identified as black or African American, and 40% are ≤40 years old, with 16% of participants46% of all procedures, with laparoscopic or robotic myomectomy comprising the largest subset of myomectomies at 19% of all procedures. Hysterectomy is the second most common treatment within the registry at 38%. CONCLUSION: In response to priorities that were identified by our patient stakeholders, the initial aims within COMPARE-UF will address how different procedures that are used to treat uterine fibroids compare in terms of long-lasting symptom relief, potential for recurrence, medical complications, improvement in quality of life and sexual function, age at menopause, and fertility and pregnancy outcomes. COMPARE-UF will generate evidence on the comparative effectiveness of different procedural options for uterine fibroids and help patients and their caregivers make informed decisions that best meet an individual patient\u27s short- and long-term preferences. Building on this infrastructure, the COMPARE-UF team of investigators and stakeholders, including patients, collaborate to identify future priorities for expanding the registry, such as assessing the efficacy of medical therapies for uterine fibroids. COMPARE-UF results will be disseminated directly to patients, providers, and other stakeholders by traditional academic pathways and by innovative methods that include a variety of social media platforms. Given demographic differences among women who undergo different uterine fibroid treatments, the assessment of comparative effectiveness for this disease through clinical trials will remain difficult. Therefore, this registry provides optimized evidence to help patients and their providers better understand the pros and cons of different treatment options so that they can make more informed decisions