Neuroanatomical correlates of the near response: voluntary modulation of accommodation/vergence in the human visual system

This study identifies brain regions participating in the execution of eye movements for voluntary positive accommodation (VPA) during open-loop vergence conditions. Neuronal activity was estimated by measurement of changes in regional cerebral blood flow (rCBF) with positron emission tomography and 15O-water. Thirteen naive volunteers viewed a checkerboard pattern with their dominant right eye, while a lens interrupted the line of gaze during alternate 1.5 s intervals. Three counterbalanced tasks required central fixation and viewing of a stationary checkerboard pattern: (i) through a 0.0 diopter (D) lens; (ii) through a -5.0-D lens while avoiding volitional accommodation and permitting blur; and (iii) through a -5. 0-D lens while maintaining maximal focus. The latter required large-amplitude, high-frequency VPA. As an additional control, seven of the subjects viewed passively a digitally blurred checkerboard through a 0.0-D lens as above. Optometric measurements confirmed normal visual acuity and ability to perform the focusing task (VPA). Large-amplitude saccadic eye movements, verified absent by electro-oculography, were inhibited by central fixation. Image averaging across subjects demonstrated multifocal changes in rCBF during VPA: striate and extrastriate visual cortices; superior temporal cortices; and cerebellar cortex and vermis. Decreases in rCBF occurred in the lateral intraparietal area, prefrontal and frontal and/or supplementary eye fields. Analysis of regions of interest in the visual cortex showed systematic and appropriate task dependence of rCBF. Activations may reflect sensorimotor processing along the reflex arc of the accommodation system, while deactivations may indicate inhibition of systems participating in visual search.     

Imatinib inhibits proliferation of Ewing tumor cells mediated by the stem cell factor/KIT receptor pathway, and sensitizes cells to vincristine and doxorubicin-induced apoptosis.

PURPOSE AND EXPERIMENTAL DESIGN: The stem cell factor/KIT receptor loop may represent a novel target for molecular-based therapies of Ewing tumor. We analyzed the in vitro impact of KIT blockade by imatinib in Ewing tumor cell lines. RESULTS: KIT expression was detected in 4 of 4 Ewing tumor cell lines and in 49 of 110 patient samples (44.5%) by immunohistochemistry and/or Western blot analysis. KIT expression was stronger in Ewing tumors showing EWS-FLI1 nontype 1 fusions. Despite absence of c-kit mutations, constitutive and ligand-inducible phosphorylation of KIT was found in all tumor cell lines, indicating an active receptor. Treatment with KIT tyrosine kinase inhibitor imatinib (0.5-20 micro M) induced down-regulation of KIT phosphorylation and dose response inhibition of cell proliferation (IC(50), 12-15 micro M). However, imatinib administered alone at doses close to IC(50) for growth inhibition (10 micro M) did not induce a significant increase in apoptosis. We then analyzed if blockade of KIT loop through imatinib (10 micro M) was able to increase the antitumor in vitro effect of doxorubicin (DXR) and vincristine (VCR), drugs usually used in Ewing tumor treatment. Addition of imatinib decreased in 15-20 and 15-36% of the proliferative rate of Ewing tumor cells exposed to DXR and VCR, respectively, and increased in 15 and 30% of the apoptotic rate of Ewing tumor cells exposed to the same drugs. CONCLUSIONS: Inhibition of Ewing tumor cell proliferation by imatinib is mediated through blockade of KIT receptor signaling. Inhibition of KIT increases sensitivity of these cells to DXR and VCR. This study supports a potential role for imatinib in the treatment of Ewing tumor.     

Phase II study of denileukin diftitox for relapsed/refractory B-Cell non-Hodgkin's lymphoma.

PURPOSE: Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL. PATIENTS AND METHODS: Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 microg/kg once daily for 5 days every 3 weeks, up to eight cycles. RESULTS: Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25- histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient. CONCLUSION: Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25- B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted.     

Hispanic health status in Orange County, Florida.

PURPOSE: To assess the health status of the Hispanic population of Orange County, Florida. METHODS: The methodology utilized secondary data for 66 ethnically identified indicators in a comparative framework applied for a 5-year period (1997-2001). FINDINGS: Orange County Hispanics are younger with lower per capita income than their Florida peers, less likely to be White, and much more likely to be of Puerto Rican origin. Relative to the Hispanic populations in the selected peer counties and statewide, Orange County Hispanics have higher age-adjusted death rates for a majority of disease categories and conditions, such as breast, lung, and prostate cancers; chronic liver disease and cirrhosis; diabetes mellitus; pneumonia and influenza; stroke; acquired immunodeficiency syndrome; motor vehicle accidents; and infant, neonatal, and child mortality. Orange County Hispanics did better in comparison to Orange non-Hispanics, with lower age-adjusted death rates for major causes of death such as heart disease, cancer, and stroke. However, for many indicators, the 5-year trends for Orange County Hispanics are moving in an unfavorable direction in contrast to the trends for non-Hispanics, which are either stable or improving. CONCLUSION: Comparative assessments of Hispanic populations using secondary data enable the development of a comprehensive health status profile. However, this approach is currently constrained by the limited number of ethnically identified indicators and, especially for Hispanics, problems in the accuracy and consistency of the assignment to racial categories and subsequent reporting.     

An interactive and contextual model of community-university collaborations for research and action.

Community-university partnerships for research and action are at the heart of many fields in the social sciences including public health, urban planning, education, and community psychology. These partnerships involve individuals from different backgrounds and disciplines working together to address social issues of importance to the community. This article proposes an interactive and contextual model for developing and sustaining community-university partnerships. The phases in the model include gaining entry into the community, developing and sustaining a mutual collaboration (developing trust and mutual respect, establishing adequate communication, respecting human diversity, establishing a culture of learning, respecting the culture of the setting and the community, and developing an action agenda), and recognizing the benefits and outcomes of partnership work. The model also includes the potential challenges that might threaten the partnership, such as resource inequality and time commitment.     

Randomized phase II trial of carboplatin versus paclitaxel and carboplatin in platinum-sensitive recurrent advanced ovarian carcinoma: a GEICO (Grupo Espanol de Investigacion en Cancer de Ovario) study.

BACKGROUND: The aim of this study was to determine whether the response rate for the paclitaxel-carboplatin combination is superior to carboplatin alone in the treatment of patients with platinum-sensitive recurrent ovarian carcinoma. PATIENTS AND METHODS: Patients with recurrent ovarian carcinoma, 6 months after treatment with a platinum-based regimen and with no more than two previous chemotherapy lines, were randomized to receive carboplatin area under the curve (AUC) 5 (arm A) or paclitaxel 175 mg/m(2) + carboplatin AUC 5 (arm B). The primary end point was objective response, following a 'pick up the winner' design. Secondary end points included time to progression (TTP), overall survival, tolerability and quality of life (QoL). RESULTS: Eighty-one patients were randomized and included in the intention-to-treat analysis. The response rate in arm B was 75.6% [26.8% complete response (CR) + 48.8% partial response (PR)] [95% confidence interval (CI) 59.7% to 87.6%] and 50% in arm A (20% CR + 30% PR) (95% CI 33.8% to 66.2%). No significant differences were observed in grade 3-4 hematological toxicity. Conversely, mucositis, myalgia/arthralgia and peripheral neurophaty were more frequent in arm B. Median TTP was 49.1 weeks in arm B (95% CI 36.9-61.3) and 33.7 weeks in arm A (95% CI 25.8-41.5). No significant differences were found in the QoL analysis. CONCLUSIONS: Paclitaxel-carboplatin combination is a tolerable regimen with a higher response rate than carboplatin monotherapy in platinum-sensitive recurrent ovarian carcinoma.     

Reliability and agreement of adipose tissue fat fraction measurements with water–fat MRI in patients with manifest cardiovascular disease

The supraclavicular fat depot is known for brown adipose tissue presence. To unravel adipose tissue physiology and metabolism, high quality and reproducible imaging is required. In this study we quantified the reliability and agreement of MRI fat fraction measurements in supraclavicular and subcutaneous adipose tissue of 25 adult patients with clinically manifest cardiovascular disease. MRI fat fraction measurements were made under ambient temperature conditions using a vendor supplied mDixon chemical‐shift water–fat multi‐echo pulse sequence at 1.5 T field strength. Supraclavicular fat fraction reliability (intraclass correlation coefficient_agreement, ICC_agreement) was 0.97 for test–retest, 0.95 for intra‐observer and 0.56 for inter‐observer measurements, which increased to 0.88 when ICC_consistency was estimated. Supraclavicular fat fraction agreement displayed mean differences of 0.5% (limit of agreement (LoA) ?1.7 to 2.6) for test–retest, ?0.5% (LoA ?2.9 to 2.0) for intra‐observer and 5.6% (LoA 0.4 to 10.8) for inter‐observer measurements. Median fat fraction in supraclavicular adipose tissue was 82.5% (interquartile range (IQR) 78.6–84.0) and 89.7% (IQR 87.2–91.5) in subcutaneous adipose tissue (p < 0.0001). In conclusion, water–fat MRI has good reliability and agreement to measure adipose tissue fat fraction in patients with manifest cardiovascular disease. These findings enable research on determinants of fat fraction and enable longitudinal monitoring of fat fraction within adipose tissue depots. Interestingly, even in adult patients with manifest cardiovascular disease, supraclavicular adipose tissue has a lower fat fraction compared with subcutaneous adipose tissue, suggestive of distinct morphologic characteristics, such as brown adipose tissue. Copyright © 2015 John Wiley & Sons, Ltd.