ERß- and prostaglandin E2-regulated pathways integrate cell proliferation via Ras-like and estrogen-regulated growth inhibitor in endometriosis.

In endometriosis, stromal and epithelial cells from the endometrium form extrauterine lesions and persist in response to estrogen (E2) and prostaglandin E2 (PGE2). Stromal cells produce excessive quantities of estrogen and PGE2 in a feed-forward manner. However, it is unknown how estrogen stimulates cell proliferation and survival for the establishment and persistence of disease. Previous studies suggest that estrogen receptor-ß (ERß) is strikingly overexpressed in endometriotic stromal cells. Thus, we integrated genome-wide ERß binding data from previously published studies in breast cells and gene expression profiles in human endometriosis and endometrial tissues (total sample number = 81) and identified Ras-like, estrogen-regulated, growth inhibitor (RERG) as an ERß target. Estradiol potently induced RERG mRNA and protein levels in primary endometriotic stromal cells. Chromatin immunoprecipitation demonstrated E2-induced enrichment of ERß at the RERG promoter region. PGE2 via protein kinase A phosphorylated RERG and enhanced the nuclear translocation of RERG. RERG induced the proliferation of primary endometriotic cells. Overall, we demonstrated that E2/ERß and PGE2 integrate at RERG, leading to increased endometriotic cell proliferation and represents a novel candidate for therapeutic intervention.

Ligand-activated peroxisome proliferator-activated receptor ß/δ modulates human endometrial cancer cell survival.

Endometrial cancer is the fourth most common malignancy among women and is a major cause of morbidity contributing to approximately 8,200 annual deaths in the USA. Despite advances to the understanding of endometrial cancer, novel interventions for the disease are necessary given that many tumors become refractory to therapy. As a strategy to identify novel therapies for endometrial carcinoma, in this study, we examined the contribution of the peroxisome proliferator-activated receptor ß/δ (PPARß/δ) to endometrial cancer cell proliferation and apoptosis. We found that when activated with the highly selective PPARß/δ agonists, GW0742 and GW501516, PPARß/δ inhibited the proliferation and markedly induced the apoptosis of three endometrial cancer cell lines. The specificity of the PPARß/δ-induced effects on cell proliferation and apoptosis was demonstrated using PPARß/δ-selective antagonists and PPARß/δ small interfering RNA in combination with PPARß/δ-selective agonists. Furthermore, we showed that PPARß/δ activation increased phosphatase and tensin homolog expression, which led to protein kinase B (AKT) and glycogen synthase kinase-3ß (GSK3ß) dephosphorylation, and increased ß-catenin phosphorylation associated with its degradation. Overall, our data suggest that the antitumorigenic effect of PPARß/δ activation in endometrial cancer is mediated through the negative regulation of the AKT/GSK3ß/ß-catenin pathway. These findings warrant further investigation of PPARß/δ as a therapeutic target in endometrial cancer.

Gaining commitment to rehabilitation: importance of preoperative assessment.

Assessment and psychological concerns in caring for the child and parents contemplating pediatric microsurgery to repair hand defects are issues nurses will face. Assessing the patient's perception of self, assessing the perception of expected postoperative results, and assessing the parents' adjustment to the disability will be discussed in this article.

Nonsurgically treated carpal tunnel syndrome in the manual worker.

This study evaluates the course of carpal tunnel syndrome in a group of manual laborers who declined surgery for personal or social reasons. Thirty-five patients and 67 extremities with carpal tunnel syndrome were evaluated in a group of manual laborers. The carpal tunnel syndrome was classified as mild, moderate, or severe on the basis of initial evaluation data. Sensory batteries, motor and sensory conduction velocities, and electrical studies were performed on a scheduled basis. Follow-up ranged between 14 and 58 months, with an average of 34.3 months. Three patients became worse and one improved during the study period. All others remained unchanged. Six patients returned to work, but only three returned to their original jobs. Although carpal tunnel syndrome does not appear to be a progressive condition once the triggering cause is removed, nonsurgical treatment does not seem to be the treatment of choice for patients who must continue in a manual labor position.

Treatment for clients with cumulative trauma disorders: using an educational model to communicate choices.

1. Cumulative trauma disorders comprise more than half of all occupational injuries reported in the U.S. 2. Lack of clear definition about cumulative trauma disorders causes confusion for clients in the workers' compensation system. 3. A teaching poster about cumulative trauma disorders was developed (describing prevention, acute care, and rehabilitation) to assist clients in understanding this disorder. Emphasis was placed on clients' choice in decision making about treatment. 4. Evaluation was carried out using a survey questionnaire. The majority of clients thought the poster was "helpful" or "very helpful." Actual behavioral change was most noticeable in the categories of "took steps to reduce risk factors" and "asked more questions about care."

The association of peripheral nerve compression and reflex sympathetic dystrophy.

35 patients who presented with reflex sympathetic dystrophy (RSD) are reported. Peripheral nerve compression was present in 86% of the patients (30). 50% of the patients (15) had a single nerve compression, and 50% had multiple nerve compressions. The high incidence of these entrapments should alert the clinician to check for this treatable problem early in the course of RSD.