Intratumor versus intertumor heterogeneity in gene expression profiles of soft-tissue sarcomas

Soft-tissue sarcomas (STSs) constitute more than 30 histologic entities. In addition, within each entity, tumors are often heterogeneous in macroscopic features, genetic alterations, microscopic appearance, and clinical course. Therefore, there has been concern about whether a single tumor sample can provide a gene expression profile representative of the entire tumor. We used 27-k cDNA microarray slides to assess the importance of intratumor versus intertumor heterogeneity of the gene expression profiles of 2 morphologically heterogeneous STSs. Multiple pieces of tumor (8 and 10 pieces) were obtained from a myxoid variant of malignant fibrous histiocytoma (MFH) and a leiomyosarcoma (LMS), respectively, and the expression patterns were compared with single tumor samples from 20 MFHs and 16 LMSs. Hierarchical clustering analysis of the expression profiles showed that samples from the same tumor clustered together. The average intratumor distance was considerably shorter than the average intertumor distance in both LMS and MFH. In addition, tumor subclusters that distinguished different macroscopic parts of the tumor could be discerned. We concluded that intratumor variability exists but that accurate gene expression profiling also could be obtained using single samples from a large STS.     

Wireless technology improves nursing workflow and communications

Inpatient healthcare delivery involves complex processes that require interdisciplinary teamwork and frequent communication among physicians, nurses, unit secretaries, and ancillary staff. Often, these interactions are not at a nursing unit, or near a phone. In an effort to address the inefficiencies of these workflow processes and communications, St. Agnes HealthCare, Baltimore, MD, installed a new hands-free communications system that uses a wireless network, voice recognition, and a small wearable badge. Developed by Vocera, the communications system permits one-button access to others on the system or connects to outside phones through PBX integration. While many agree that today's technology has the potential to positively impact nursing care delivery, St. Agnes HealthCare and Vocera, with assistance from First Consulting Group, decided to conduct a comprehensive benefits study in December 2003 to quantify the impact of this communications system on workflow and communications. The results identified a number of significant findings that demonstrate its value from a quantitative and qualitative standpoint. The following article describes this study and its findings.     

A framework for assessing risks to children from exposure to environmental agents

In recent years there has been an increasing focus in environmental risk assessment on children as a potentially susceptible population. There also has been growing recognition of the need for a systematic approach for organizing, evaluating, and incorporating the available data on children's susceptibilities in risk assessments. In this article we present a conceptual framework for assessing risks to children from environmental exposures. The proposed framework builds on the problem formulation-->analysis-->risk characterization paradigm, identifying at each phase the questions and issues of particular importance for characterizing risks to the developing organism (from conception through organ maturation). The framework is presented and discussed from the complementary perspectives of toxicokinetics and toxicodynamics.     

p42/44MAPK regulates baseline permeability and cGMP-induced hyperpermeability in endothelial cells

We tested the hypothesis that p42/44MAPK and p38MAPK (mitogen-activated protein kinases; MAPK) signaling pathways regulate endothelial cell permeability to macromolecules. Passage 2-4 human umbilical vein endothelial cells (HUVEC) were grown to confluence on fibronectin-coated Snapwell membranes. The flux of fluorescein isothiocyanate-labeled dextran-70 across the HUVEC monolayers served to determine permeability. Application of 1 mM 8-bromo 3' 5'-cyclic guanosine monophosphate (8-Br-cGMP) increased permeability from 7.0 +/- 1.6 x 10(-6) to 12.5 +/- 2.8 x 10(-6) cm/s (P < 0.05). Pretreatment of HUVEC for 60 min with a selective p42/44MAPK inhibitor (AG126 at 2.7 and 27 microM) blocked 8-Br-cGMP-induced hyperpermeability. However, inhibition of p38MAPK (SB203580 at 0.6 microM) did not influence the cGMP-induced hyperpermeability response. AG126, administered at 27 microM, decreased baseline permeability from 7.9 +/- 0.5 x 10(-6) to 5.9 +/- 0.5 x 10(-6) cm/s (P < 0.05). Our results indicate that the p42/44MAPK signaling pathway is important in the regulation of baseline permeability and cGMP-induced hyperpermeability.     

Association between insulin-like growth factor status and physical activity levels in rheumatoid arthritis

OBJECTIVE: To determine if the altered insulin-like growth factor (IGF) status in rheumatoid arthritis (RA) is due to inflammation, altered body composition, or lack of exercise. METHODS: Subjects included 73 patients with RA, 54 patients with other rheumatic diseases, both inflammatory and noninflammatory, and 28 healthy, physically active controls. Serum levels of IGF-I, IGF-II, and IGF binding protein-3 (IGFBP-3) were measured by radioimmunoassay. Body composition was estimated by bioelectrical impedance analysis, and habitual exercise level approximated by questionnaire. Statistical analysis was performed by 2 and 3 way ANOVA and moderated hierarchical regression. RESULTS: Serum IGF-I (p < 0.001), IGFBP-3 (p < 0.001), and the BP-3:total IGF molar ratio (p < 0.001) were depressed in both patient groups relative to controls. In contrast, IGF-II levels were depressed only in patients with RA (p < 0.01). Differences in the IGF proteins between patients and controls could not be attributed to inflammation. Habitual exercise level, but not body composition, was shown to be a significant predictor for IGF-I, IGFBP-3, and BP-3:total IGF molar ratio (p < 0.001). CONCLUSION: Our results indicate that the reduction in circulating IGF proteins observed in our patients is more related to their sedentary lifestyle than to the inflammatory process. This conclusion is in agreement with reports that show that highly active individuals typically exhibit higher levels of systemic IGF proteins than age matched sedentary controls.     

Special considerations in breast cancer risk and survival.

Experimental and clinical evidence suggests that breast neoplasia appears to be a hormone-dependent process that may also be influenced by dietary factors in many women. Conflicting reports on the relationship between exogenous hormones and the development, progression, and recurrence of breast cancer are critically examined in this report. The absolute breast cancer risk associated with either hormone replacement therapy or oral contraceptive use has not been clearly defined. Data from some large prospective studies have actually documented lower mortality rates for women taking hormone replacement compared with those for women who did not have hormone replacement therapy. In this regard, age, duration of use, and preexisting breast cancer risk factors must be taken into account. Although the results of two major prospective clinical trials addressing the role of timing of surgery within the menstrual cycle are forthcoming, the majority of studies have found no consistent association between timing of surgery and breast cancer survival. Recently reported prospective randomized data showing that selective-estrogen-receptor-modulators can act as effective chemoprevention agents in women at increased risk for breast cancer development are presented. Finally, information regarding the effect of dietary manipulation on breast cancer risk and survival is reviewed.