Biomedical subjects

Elizabeth Garrett-Mayer

Publications and source records attributed to Elizabeth Garrett-Mayer.

26 records · Page 2Linked to original sources

PubMed2004

Epigenetic regulation of protein phosphatase 2A (PP2A), lymphotactin (XCL1) and estrogen receptor alpha (ER) expression in human breast cancer cells.

Absence of the estrogen receptor alpha (ER) in human breast cancer cells is an indicator of poor prognosis, and predictive of lack of response to hormonal therapy. Previous studies in our laboratory and others have shown that epigenetic regulation, including DNA methylation and histone deacetylation, are common mechanisms leading to ER gene silencing. Through the use of pharmacologic inhibitors, 5-aza 2'deoxycytidine (AZA) and Trichostatin A (TSA), we have shown that alterations in both of these mechanisms results in synergistic reexpression of ER mRNA and functional protein. These alterations may play a larger role in stimulation of cell signaling pathways leading to ER expression. We have utilized newly developed genome wide screening microarray techniques to identify gene(s) contributing to the hormone independent phenotype and AZA/TSA mediated ER expression. From this screen, we identified and confirmed expression of 4 candidate genes (PP2A, XCL1, THY1 and NBC4) as potential regulators of the hormone independent phenotype. Expression of two genes, XCL1 and PP2A, appeared to be correlated with ER expression. PP2A expression was not changed with ER degradation using ICI 182,780 whereas XCL1 expression decreased in the presence of AZA/TSA and ICI 182,780. This suggests that PP2A may be a determinant of ER expression while XCL1 appears to be ER responsive and downstream of ER expression. These gene products may be novel targets to be further explored in the development of new therapeutics for ER negative breast cancer.

Acetylation↗

PubMed2004

Gene expression alterations over large chromosomal regions in cancers include multiple genes unrelated to malignant progression.

In solid tumors, the relationship between DNA copy number and global expression over large chromosomal regions has not been systematically explored. We used a 12,626-gene expression array analysis of head and neck squamous cell carcinoma and normal oral mucosa and annotated gene expression levels to specific chromosomal loci. Expression alterations correlated with reported data using comparative genomic hybridization. When genes with significant differences in expression between normal and malignant lesions, as defined by significance analysis of microarrays (SAM), were compared to nonsignificant genes, similar chromosomal patterns of alteration in expression were noted. Individual tumors underwent microsatellite analysis and chi(2) analysis of expression at 3p and 22q. Significant 3p underexpression and 22q overexpression were found in all primary tumors with 3p and 22q allelic imbalance, respectively, whereas no tumor without allelic imbalance on these chromosomal arms demonstrated expression differences. Loss and gain of chromosomal material in solid cancers can alter gene expression over large chromosomal regions, including multiple genes unrelated to malignant progression.

Allelic Imbalance↗

PubMed2004

Very high frequency of hypermethylated genes in breast cancer metastasis to the bone, brain, and lung.

PURPOSE: Most often it is not the primary tumor, but metastasis to distant organs that results in the death of breast cancer patients. To characterize molecular alterations in breast cancer metastasis, we investigated the frequency of hypermethylation of five genes (Cyclin D2, RAR-beta, Twist, RASSF1A, and HIN-1) in metastasis to four common sites: lymph node, bone, brain, and lung. EXPERIMENTAL DESIGN: Methylation-specific PCR for the five genes was performed on DNA extracted from archival paraffin-embedded specimens of paired primary breast cancer and its lymph nodes (LN) metastasis (n = 25 each); in independent samples of metastasis to the bone (n = 12), brain (n = 8), and lung (n = 10); and in normal bone, brain, and lung (n = 22). RESULTS: No hypermethylation was detected in the five genes in the normal host tissues. In paired samples, LN metastasis had a trend of higher prevalence of methylation compared with the primary breast carcinoma for all five genes with significance for HIN-1 (P = 0.04). Compared with the primary breast carcinomas, all five genes had higher methylation frequencies in the bone, brain, and lung metastasis, with HIN-1 and RAR-beta methylation being significantly higher (P < 0.01) in each group. Loss of expression of all five genes correlated, with a few exceptions, to hypermethylation of their promoter sequences in metastatic carcinoma cells microdissected from LNs. CONCLUSION: The frequent presence of hypermethylated genes in locoregional and distant metastasis could render them particularly susceptible to therapy targeted toward gene reactivation combining demethylating agents, histone deacetylase inhibitors, and/or differentiating agents.

Bone Neoplasms↗

PubMed2004

Comparison of "B" readers' interpretations of chest radiographs for asbestos related changes.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine if chest radiographic interpretations by physicians retained by attorneys representing persons alleging respiratory changes from occupational exposure to asbestos would be confirmed by independent consultant readers. MATERIALS AND METHODS: For 551 chest radiographs read as positive for lung changes by initial "B" readers retained by plaintiffs' attorneys, 492 matching interpretative reports were made available to the authors. Six consultants in chest radiology, also B readers, agreed to re-interpret the radiographs independently without knowledge of their provenance. The film source, patient name, and other identifiers on each film were masked. The International Labor Office 1980 Classification of Chest Radiographs(ILO 80) was used with forms designed by the US National Institute of Occupational Safety and Health to record the consult-ants' findings. The results were compared with initial readings for film quality, complete negativity, parenchymal abnormalities,small opacities profusion, and pleural abnormalities using chi-square tests and kappa statistics.Results. Initial readers interpreted study radiographs as positive for parenchymal abnormalities (ILO small opacity profusion category of 1/0 or higher) in 95.9% of 492 cases. Six consultants classified the films as 1/0 or higher in 4.5% of 2,952 readings. Statistical tests of these and other comparable data from the study showed highly significant differences between the interpretations of the initial readers and the findings of the consultants. CONCLUSION: The magnitude of the differences between the interpretations by initial readers and the six consultants is too great to be attributed to interobserver variability. There is no support in the literature on x-ray studies of workers exposed to asbestos and other mineral dusts for the high level of positive findings recorded by the initial readers in this report.

Asbestosis↗

PubMed2004

Effect of calcium channel blockers on the sensitivity of preoperative 99mTc-MIBI SPECT for hyperparathyroidism.

BACKGROUND: Technetium 99m ( 99m Tc)-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) is frequently used in the evaluation of patients with hyperparathyroidism. Calcium channel blockers (CACBs) may affect 99m Tc-MIBI uptake by parathyroid cells. This study examines the effect of CACB therapy on the sensitivity of 99m Tc-MIBI SPECT localization for hyperparathyroidism. METHODS: Two hundred fifty-three operated patients with hyperparathyroidism were retrospectively reviewed. The potential effect of CACB therapy on 99m Tc-MIBI scan sensitivity was examined by using logistic regression analysis. Possible confounding factors were considered. RESULTS: Among 235 patients, those with multiple endocrine neoplasia, type I (MEN-I), MEN-IIA, 4-gland hyperplasia, secondary hyperparathyroidism, and tertiary hyperparathyroidism exhibited no difference associated with CACB use. Of the remaining 198 patients with primary hyperparathyroidism, 7/30 (23%) with negative 99m Tc-MIBI SPECT scans compared to 24/168 (14%) with positive scans used CACBs. After correcting for age, gender and gland weight, the odds ratio (OR) for a negative study in patients taking CACBs was 2.88 (95% CI, 1.03-8.10; P = .045). Atherosclerosis, hypertension, diabetes mellitus, preoperative calcium and parathyroid hormone levels, and thyroid hormone use were not confounding factors. CONCLUSIONS: CACB therapy reduces the sensitivity of 99m Tc-MIBI parathyroid SPECT in patients with primary hyperparathyroidism. Further studies are required to determine the potential reversibility of this effect with termination of CACB therapy.

Calcium Channel Blockers↗

PubMed2004

Eliminating catheter-related bloodstream infections in the intensive care unit.

OBJECTIVE: To determine whether a multifaceted systems intervention would eliminate catheter-related bloodstream infections (CR-BSIs). DESIGN: Prospective cohort study in a surgical intensive care unit (ICU) with a concurrent control ICU. SETTING: The Johns Hopkins Hospital. PATIENTS: All patients with a central venous catheter in the ICU. INTERVENTION: To eliminate CR-BSIs, a quality improvement team implemented five interventions: educating the staff; creating a catheter insertion cart; asking providers daily whether catheters could be removed; implementing a checklist to ensure adherence to evidence-based guidelines for preventing CR-BSIs; and empowering nurses to stop the catheter insertion procedure if a violation of the guidelines was observed. MEASUREMENT: The primary outcome variable was the rate of CR-BSIs per 1,000 catheter days from January 1, 1998, through December 31, 2002. Secondary outcome variables included adherence to evidence-based infection control guidelines during catheter insertion. MAIN RESULTS: Before the intervention, we found that physicians followed infection control guidelines during 62% of the procedures. During the intervention time period, the CR-BSI rate in the study ICU decreased from 11.3/1,000 catheter days in the first quarter of 1998 to 0/1,000 catheter days in the fourth quarter of 2002. The CR-BSI rate in the control ICU was 5.7/1,000 catheter days in the first quarter of 1998 and 1.6/1,000 catheter days in the fourth quarter of 2002 (p = .56). We estimate that these interventions may have prevented 43 CR-BSIs, eight deaths, and 1,945,922 dollars in additional costs per year in the study ICU. CONCLUSIONS: Multifaceted interventions that helped to ensure adherence with evidence-based infection control guidelines nearly eliminated CR-BSIs in our surgical ICU.

Catheterization, Central Venous↗

PubMedDate not supplied

Does it pay to pay? A randomized trial of prepaid financial incentives and lottery incentives in surveys of nonphysician healthcare professionals.

BACKGROUND: Monetary incentives in survey research may provide important gains from a methodological perspective in the control and reduction of survey error associated with potential nonresponse of participants. However, few studies have systematically investigated the use of monetary incentives or other methods to improve the response rates in the nonphysician clinician population. OBJECTIVE: To investigate differences in response rates to a mailed self-administered survey of nonphysician clinicians who were randomized to receive a prepaid monetary incentive, a postsurvey prize drawing, or no incentive. METHODS: A randomized controlled trial of financial incentives was conducted from November 2002 to February 2003. Nonphysician clinicians (nurse practitioners [NPs] and physician assistants [PAs]; N = 3,900) randomly selected to participate in a national ethics-related study were assigned randomly in equal allocations (n = 1,300 [650 NPs, 650 PAs]) to three incentive groups: (a) no incentive; (b) a $5 prepaid token incentive in the initial mailing; or (c) a chance to win one of ten $100 prize drawings upon completion and return of a self-administered survey. RESULTS: A $5 cash incentive increased survey response rates to an adjusted 64.2%: a 19.5 percentage point increase over the lottery group (44.7% response rate), and a 22 percentage point increase over the control group (42.2% response rate). DISCUSSION: A nominal cash incentive of $5 yields a significantly higher response rate from nonphysician providers than receiving either a lottery option or no incentive.

Adult↗

PubMedDate not supplied

Ethical conflict in nurse practitioners and physician assistants in managed care.

BACKGROUND: More patients are receiving healthcare services from nurse practitioners (NPs) and physician assistants (PAs). These providers are likely to be confronted with a variety of ethical issues as they balance quality care with their patients' rising cost concerns. However, very little is known about the ethical conflicts and causes of these conflicts experienced by these clinicians in their daily practice. OBJECTIVE: To identify ethical concerns and conflicts NPs and PAs encounter related to managed care in the delivery of primary care to patients and the factors that influence ethical conflict. METHODS: A cross-sectional self-administered mailed questionnaire was sent to 3,900 NPs and PAs randomly selected from primary care and primary care subspecialties in the United States (adjusted response rate, 50.6%). Respondents were surveyed on ethical issues and concerns, ethics preparedness, and ethical conflict. Bivariate and multiple linear regression analyses were used to evaluate predictors of ethical conflict. RESULTS: Insurance constraints were reported to have interfered with the ability to provide quality patient care by 72% of respondents, with 55.3% reporting daily to weekly interferences. Nearly half of respondents (47%) have been asked by a patient to mislead insurers to assist them in receiving care. A perceived obligation to advocate for patients, even if it means exaggerating the severity of a patient's condition, was the single most significant predictor of ethical conflict, explaining 25% of the variance. DISCUSSION: NPs and PAs are experiencing ethical conflict often associated with their perceived professional obligations to advocate for patients. Being well-prepared in ethics and having sufficient professional independence help clinicians balance the ethical complexities and demands of meeting patients' needs within a constrained healthcare system.

Adult↗