Medicine and Health Sciences Commons^™

Chronic Intrauterine Infection And Inflammation In The Preterm Rabbit, Despite Antibiotic Therapy, R. Gibbs, J. Davies, R. Mcduffie, Kimberly Leslie, M. Sherman, C. Centretto, D. Wolf

Kimberly K. Leslie

OBJECTIVE: In a pregnant rabbit model using intracervical inoculation of Escherichia coli with delayed antibiotic therapy, we investigated the rate of positive cultures and histologic inflammation of maternal and fetal compartments and the concentration of tumor necrosis factor-alpha in the amniotic fluid for up to 5 days. STUDY DESIGN: New Zealand White rabbits at 70% gestation were inoculated intracervically with 10(3) - 10(4) colony-forming units of E coli per uterine horn. At varying intervals after inoculation (0.5 - 4.0 hours), antibiotic therapy was initiated with ampicillin-sulbactam. Primary outcomes were positive cultures and histologic inflammation score. Tumor necrosis factor-alpha levels in …

Egfr Isoforms And Gene Regulation In Human Endometrial Cancer Cells, L. Albitar, G. Pickett, M. Morgan, J. Wilken, N. Maihle, Kimberly Leslie

Kimberly K. Leslie

BACKGROUND: Epidermal growth factor (EGF) and its receptor (EGFR) constitute a principal growth-promoting pathway in endometrial cancer cells. Pre-clinical studies were undertaken to compare the expression of EGFR isoforms and the downstream effects of activating or blocking EGFR function in Ishikawa H cells, derived from a moderately differentiated type I endometrioid adenocarcinoma, or in Hec50co cells, derived from a poorly differentiated type II adenocarcinoma with papillary serous sub-differentiation. RESULTS: We investigated whether EGFR mutations are present in the tyrosine kinase domain (exons 18-22) of EGFR and also whether EGFR isoforms are expressed in the Ishikawa H or Hec50co cell lines. …

Lapatinib And Potential Prognostic Value Of Egfr Mutations In A Gynecologic Oncology Group Phase Ii Trial Of Persistent Or Recurrent Endometrial Cancer, Kimberly Leslie, M. Sill, H. Lankes, E. Fischer, A. Godwin, H. Gray, R. Schilder, J. Walker, K. Tewari, P. Hanjani, O. Abulafia, P. Rose

Kimberly K. Leslie

OBJECTIVE: A phase II trial was performed to evaluate the efficacy and safety of the tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and HER2, lapatinib, and to explore EGFR, HER2 (EGFR2), phosphorylated ERK MAP kinase (pERK), and Ki67 expression, as well as EGFR mutations in persistent/recurrent endometrial cancer (EC). METHODS: Women with histologically-confirmed, measurable, persistent/recurrent EC following one or two prior regimens were eligible and treated with 1500 mg oral lapatinib daily until progression or severe toxicity. A 2-stage group sequential design was used to evaluate the regimen with 6 month PFS as the primary endpoint. The trial …

Progesterone Inhibits Human Endometrial Cancer Cell Growth And Invasiveness: Down-Regulation Of Cellular Adhesion Molecules Through Progesterone B Receptors, Donghai Dai, D. Wolf, E. Litman, M. White, Kimberly Leslie

Kimberly K. Leslie

Progesterone is a critical steroid hormone that controls cell proliferation and differentiation in the female reproductive tract. Progesterone acts through two nuclear receptor isoforms, progesterone receptors A and B (PRA and PRB, respectively), each with unique cellular effects. Loss of PRB has recently been linked to the development of poorly differentiated endometrial tumors, a lethal form of cancer. To study the molecular effects of progesterone, progesterone receptors were introduced into Hec50co endometrial cancer cells by adenoviral vectors encoding either PRA or PRB. Progesterone induced the cyclin-dependent kinase inhibitors p21 and p27, thereby significantly reducing the percentage of proliferating cells. Cancer …

Obstetric Forceps Training Using Visual Feedback And The Isometric Strength Testing Unit, Kimberly Leslie, P. Dipasquale-Lehnerz, M. Smith

Kimberly K. Leslie

OBJECTIVE: This is a descriptive study that tested the maximum traction residents could apply to forceps during simulations. Visual feedback was then used to reinforce an optimal range of traction, and the ability of residents to reproduce this pull when blinded was assessed. METHODS: Fifty-five residents participated in 6 pulling exercises using an isometric strength testing unit with a real-time computer printout of the force applied. Maximum traction was determined for male and female residents in standing and sitting positions. Visual feedback was then used to estimate whether residents could be trained to reproduce an optimal force range of 30-45 …

Models Representing Type I And Type Ii Human Endometrial Cancers: Ishikawa H And Hec50co Cells, L. Albitar, G. Pickett, M. Morgan, S. Davies, Kimberly Leslie

Kimberly K. Leslie

OBJECTIVE: Endometrial cancer models are critical to the advancement of investigation, and Ishikawa H and Hec50co cells have been used as research tools. The purpose of these studies is to verify the degree to which these commonly used cell models share the molecular characteristics of the two major in vivo endometrial cancer subtypes, I and II. METHODS: The studies reported include an analysis of pathologic features, tumor suppressor mutations, detailed karyotyping, and cell cycle regulation. RESULTS: Ishikawa H cells are hormone responsive and have lost PTEN expression. In addition they have lost RB1 expression due to a deletion in exon …

Knockdown Of Mtdh Sensitizes Endometrial Cancer Cells To Cell Death Induction By Death Receptor Ligand Trail And Hdac Inhibitor Lbh589 Co-Treatment, Xiangbing Meng, Pavla Brachova, Shujie Yang, Zhi Xiong, Yuping Zhang, Khristina Thiel, Kimberly Leslie

Kimberly K. Leslie

Understanding the molecular underpinnings of chemoresistance is vital to design therapies to restore chemosensitivity. In particular, metadherin (MTDH) has been demonstrated to have a critical role in chemoresistance. Over-expression of MTDH correlates with poor clinical outcome in breast cancer, neuroblastoma, hepatocellular carcinoma and prostate cancer. MTDH is also highly expressed in advanced endometrial cancers, a disease for which new therapies are urgently needed. In this present study, we focused on the therapeutic benefit of MTDH depletion in endometrial cancer cells to restore sensitivity to cell death. Cells were treated with a combination of tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL), which …

Oral Contraceptives And Skin Cancer: Is There A Link?, Kimberly Leslie, E. Espey

Kimberly K. Leslie

The skin expresses estrogen, progesterone, and androgen receptors. In the presence of steroid hormones, such as those contained in oral contraceptives, the skin likely responds to hormonal signals that control the cell cycle, apoptosis, DNA replication, and other cellular functions. Some estrogen-responsive pathways have the potential to promote tumor development, including the augmentation of epidermal growth factor signaling, the expression of proto-oncogenes, and inhibition of apoptosis. The question of whether oral contraceptives increase the risk for the development of skin cancer, particularly melanoma, is still an area of concern. This paper reviews the available evidence, the bulk of which suggests …

Amifostine Enhancement Of The Anti-Cancer Effects Of Paclitaxel In Endometrial Cancer Is Tp53-Dependent, W. Luo, F. Wu, R. Elmaoued, B. Beck, E. Fischer, Xiangbing Meng, Kimberly Leslie, Donghai Dai

Kimberly K. Leslie

Endometrial cancer (ECa) is the fourth most common malignancy in women. Currently, there is no effective therapy for advanced and recurrent cancer. Among the poor-outcome endometrial cancers, there is a high frequency of TP53 mutations. We have previously reported that amifostine has a direct anti-cancer effect and has a significant synergistic effect with paclitaxel when used in endometrial cancer cell and xenograft models. In this report, using a cell line with knock-down p53 expression through siRNA, we found that amifostine enhancement of paclitaxel's anticancer effect is p53 status-dependent. Amifostine promotes entry into the G2-M phase through regulation of cyclin-dependent kinase-1 …

An Exploratory Study Of The Variables Impacting Preterm Birth Rates In New Mexico, K. Gwin, R. Schrader, K. Peters, A. Moreno, K. Thiel, Kimberly Leslie

Kimberly K. Leslie

BACKGROUND: Preterm birth (PTB) is a substantial health problem that accounts for significant infant morbidity and mortality and poses an economic burden to both individuals and the state of residence. The goal of this study was to identify maternal risk factors for PTB in New Mexico, a poor state with a unique ethnic background, in order to identify populations at increased risk that would benefit from intervention. METHODS: This was a cross-sectional retrospective exploratory analysis of 377,770 singleton live births in the state of New Mexico from 1991-2005. Gestational age of less than 37 weeks was defined as PTB. The …

Breast Cancer And Pregnancy, Kimberly Leslie, C. Lange

Kimberly K. Leslie

This article addresses a challenging diagnostic and treatment dilemma encountered in the care of pregnant women-breast cancer. The treatment of a breast cancer is significantly affected by an ongoing pregnancy and may result in an increased risk for a poor outcome in the mother. The definition, incidence, mechanism, diagnosis, and treatment of breast cancer associated with pregnancy and the normal physiologic and endocrine changes in the breast during pregnancy that contribute to the difficulty encountered by practitioners in diagnosing and treating the disorder are reviewed. The risks associated with pregnancy after breast cancer treatment and the effect of pregnancy on …

Chemotherapeutic Drugs In Pregnancy, Kimberly Leslie, C. Koil, W. Rayburn

Kimberly K. Leslie

Chemotherapy may be indicated for the treatment of cancer during pregnancy. The decision to use chemotherapy significantly impacts the pregnancy, and in turn the pregnancy may affect the treatment options available to patients with cancer. This review provides information about the effects of chemotherapeutic agents in pregnancy, taking into account both the mother and the fetus. For convenience, the agents are divided into categories based upon class and mechanism of action. These include alkylating agents, antimetabolites, nucleoside analogs, topoisomerase I inhibitors, topisomerase II inhibitors, vinca alkaloids, taxanes, and biologics such as signaling and growth factor blocking agents.

An Inhibitor Of K+ Channels Modulates Human Endometrial Tumor-Initiating Cells, B. Schickling, N. Aykin-Burns, Kimberly Leslie, D. Spitz, V. Korovkina

Kimberly K. Leslie

BACKGROUND: Many potassium ion (K+) channels function as oncogenes to sustain growth of solid tumors, but their role in cancer progression is not well understood. Emerging evidence suggests that the early progenitor cancer cell subpopulation, termed tumor initiating cells (TIC), are critical to cancer progression. RESULTS: A non-selective antagonist of multiple types of K+ channels, tetraethylammonium (TEA), was found to suppress colony formation in endometrial cancer cells via inhibition of putative TIC. The data also indicated that withdrawal of TEA results in a significant enhancement of tumorigenesis. When the TIC-enriched subpopulation was isolated from the endometrial cancer cells, TEA was …

Chronic Hepatitis C In Pregnancy, E. Berkley, Kimberly Leslie, S. Arora, C. Qualls, J. Dunkelberg

Kimberly K. Leslie

OBJECTIVE: To estimate outcomes, to determine whether appropriate follow-up was performed for pregnant patients with hepatitis C virus (HCV), and to show that maternal and neonatal complications would be higher in the HCV-positive group. METHODS: We compared pregnant women from a drug dependence and treatment program who were HCV antibody-positive with those who were HCV antibody-negative using the University of New Mexico Perinatal Database. Maternal and neonatal outcomes were evaluated, including cholestasis of pregnancy, preterm birth, low birth weight, neonatal intensive care unit admissions, and neonatal methadone withdrawal. Variables were compared using Student t, Fisher exact, and chi(2) tests. RESULTS: …

Consequences Of The Loss Of P53, Rb1, And Pten: Relationship To Gefitinib Resistance In Endometrial Cancer, L. Albitar, M. Carter, S. Davies, Kimberly Leslie

Kimberly K. Leslie

OBJECTIVE: These studies demonstrate how loss of function mutations or downregulation of key tumor suppressors missing from type I and type II endometrial cancer cells contributes to carcinogenesis and to resistance to the EGFR inhibitor gefitinib (ZD1839). METHODS: Cell models devoid of tumor suppressors PTEN and RB1 or PTEN were studied. PTEN, RB1 and p53 expression was reinstated, and the effects on cell cycle, apoptosis, and cell cycle regulators were evaluated. RESULTS: In Ishikawa H cells that model type I endometrial cancer in the loss of PTEN and RB1, re-expressing PTEN and RB1 increased the apoptotic and G1 phases and …

Protocol For Determining The Diagnostic Validity Of Physical Examination Maneuvers For Shoulder Pathology., Somerville Lindsay, Dianne Bryant, Kevin Willits, Andrew Johnson

Andrew M. Johnson

No abstract provided.

Role Of The Internet As An Information Resource For Surgical Patients: A Survey Of 877 Patients, Denise Hersey, Viji Kurup, Allison Consadine

Denise Hersey

Brain Trauma, Pet Scans And Forensic Complexity, Jane Moriarty, Daniel Langleben, James Provenzale

Jane Campbell Moriarty

Positron Emission Tomography (PET) is a medical imaging technique that can be used to show brain function. Courts have admitted PET scan evidence in cases involving brain damage, injury, toxic exposure, or illness ("brain trauma") and to support claims of diminished cognitive abilities and impulse control. Despite the limited data on the relationships between PET, brain trauma and behavior, many courts admit PET scan evidence without much critical analysis. This article examines the use of PET as proof of functional impairment and justification of abnormal behavior by explaining its diagnostic use and limitations, the limited support for claims of its …