Psychometric properties of the Veterans Affairs Low-Vision Visual Functioning Questionnaire

PURPOSE: To describe psychometric properties of a self-report questionnaire, the Veterans Affairs (VA) Low-Vision Visual Functioning Questionnaire (LV VFQ-48), which was designed to measure the difficulty visually impaired persons have performing daily activities and to evaluate low-vision outcomes. METHODS: The VA LV VFQ-48 was administered by telephone interview to subjects with visual acuity ranging from near normal to total blindness at five sites in the VA and private sector. Rasch analysis with the Andrich rating scale model was applied to difficulty ratings from 367 subjects, to evaluate measurement properties of the instrument. RESULTS: High intercenter correlations for item measure estimates (intraclass correlation coefficient [ICC]=0.97) justified pooling the data from these sites. The person measure fit statistics (mean square residuals) confirm that the data fit the assumptions of the model. The item measure fit statistics indicate that responses to 19% of the items were confounded by factors other than visual ability. The separation reliabilities for pooled data (0.94 for persons and 0.98 for items) demonstrate that the estimated measures discriminate persons and items well along the visual ability dimension. ICCs for test-retest data (0.98 for items and 0.84 for persons) confirm temporal stability. Subjects used the rating categories in the same way at all five centers. Ratings of slight and moderate difficulty were used interchangeably, suggesting that the instrument could be modified to a 4-point scale including not difficult, slightly/moderately difficult, extremely difficult, and impossible. Fifty additional subjects were administered the questionnaire with a 4-point scale to confirm that the scale was used in the same way when there were four rather than five difficulty ratings. CONCLUSIONS: The VA LV VFQ-48 is valid and reliable and has the range and precision necessary to measure visual ability of low-vision patients with moderate to severe vision loss across diverse clinical settings.     

Molecular profiling of embryonal carcinoma cells following retinoic acid or histone deacetylase inhibitor treatment

Regulation of tissue homeostasis is crucial to disease prevention; cell division, cell cycle arrest, differentiation and apoptosis have to be tightly controlled in order to maintain this homeostasis. Retinoic acid (RA) and the histone deacetylase inhibitors (HDACIs) have profound effects on these processes and thus may be critical regulators of homeostasis. Consequently, RA and/or histone deacetylase inhibitors are currently being tested in clinical trials for a variety of cancers. Unfortunately, little is known of the overall affect of these compounds on cellular gene expression. Therefore, we decided to compare the effects of all-trans retinoic acid (ATRA) and a particular HDACI-Trichostatin A (TSA)-on an embryonal carcinoma (EC) cell line (F9) using gene chip analysis. We have focused particular attention on those genes that may be differentially affected by these compounds. Within the parameters established for this study, only 116 of the 12,488 genes examined were similarly regulated by ATRA and TSA: 75 positively and 41 negatively. An additional 70 genes were affected by only one of the compounds and 19 genes were actually inversely regulated. The gene set inversely regulated by ATRA and TSA includes several important patterning genes as well as the crucial tumor suppressor/promoter, transforming growth factor beta 1 (TGFbeta1). Promoter analysis suggests a motif that may regulate one set of these genes. This study provides the first comprehensive comparison of global gene expression on EC cells as affected by ATRA and a HDAC inhibitor (TSA); reveals new targets for ATRA and HDAC inhibitors; identifies a new regulatory motif; demonstrates that ATRA and HDAC inhibitors do not always act synergistically on gene expression; and examines particular questions regarding their concurrent clinical application.     

Hepatoid adenocarcinoma with liver metastasis mimicking hepatocellular carcinoma: an immunohistochemical and molecular study of eight cases

Hepatoid adenocarcinoma (HAC) is a special type of extrahepatic adenocarcinoma, which has a striking morphologic similarity to hepatocellular carcinoma. Seven HACs arising in the stomach and one in the lung, all with liver metastasis, were studied. They shared clinical features, such as old age, high serum alpha-fetoprotein level, aggressive behavior, and hepatic tumor in absence of risk factors for hepatocellular carcinoma (HCC). Morphologically, tumors were characterized by an admixture of tubulo-and/or papillary adenocarcinoma with hepatoid foci. In six cases, liver metastases showed an exclusive hepatoid differentiation, virtually indistinguishable from HCC with solid growth pattern. As HAC and HCC cannot be differentiated on the basis of morphology alone, differences in immunohistochemical reaction patterns would be of considerable diagnostic help. Immunostaining for CK7, CK8, CK18, CK19, CK20, alpha-fetoprotein, p-CEA, and HepPar1 revealed that hepatoid areas of both primary and metastatic HAC have a specific immunoprofile, distinctive of this entity. On the one hand, positivity of virtually all HACs for alpha-fetoprotein, CK8, CK18, and the membranous, canalicular staining for polyclonal carcinoembryonic antigen underline its hepatoid nature. On the other hand, positive staining for CK19 and CK20 and frequent negativity for HepPar1 in both primary tumors and their metastases were distinctive features of HAC. Furthermore, HAC differs from combined hepatocellular cholangiocarcinoma, being negative for CK7. In addition, for comparison of immunohistochemical results, we stained with the same antibody panel a tissue microarray of 121 HCCs. Comparative genomic hybridization study of three HAC supports their hepatoid differentiation as aberrations found in HAC are common in HCC (4q-, 8p-), and hepatoblastoma (Xq+), respectively.     

Human albumin synthesis is increased by an ultra-endurance trial

PURPOSE: The purpose of this study was to determine whether an ultra-endurance event is a strong stimulus to increase albumin synthesis involved in the process of intravascular albumin mass increase associated with transient hypervolemia. METHODS: The albumin synthetic rate was measured in six young men, 3 d before (C) and on the 1st (R1) and 8th (R8) days of the recovery from an ultra-endurance trial (5 h daily for 4 d). Albumin fractional (FSR) and absolute (ASR) synthetic rate were determined using a primed-constant infusion of [1(-13) C] leucine. Plasma volume (PV) using Evans Blue dye dilution and total body water (TBW) using bioelectrical impedance analysis were measured on C, R1, and R8. RESULTS: On R1 as compared with C: 1). PV (+23.3 +/- 3.2%; P相似文献   

Induction of CD8 T-cell-Ifn-gamma response and positive clinical outcome after immunization with gene-modified allogeneic tumor cells in advanced non-small-cell lung carcinoma

Large tumor burdens in advanced non-small-cell lung carcinoma (NSCLC) are thought to be immunosuppressive. To determine whether CD8-mediated immune responses could be elicited in stage IIIB/IV NSCLC patients, 14 subjects were immunized several times with allogeneic NSCLC cells transfected with CD80 (B7.1) and HLA-A1 or A2. Patients enrolled were matched or unmatched at the HLA A1 or A2 locus and their immune response compared. Immunization significantly increased the frequencies of interferon-gamma secreting CD8 T cells in all but one patient in response to ex vivo challenge with NSCLC cells. The CD8 response of matched and unmatched patients was not statistically different. NSCLC reactive CD8 cells did not react to K562. Clinically, five of 14 patients responded to immunization with stable disease or partial tumor regression. The study demonstrates that CD8 Ifn-gamma responses against nonimmunogenic or immunosuppressive tumors can be evoked by cellular vaccines even at advanced stages of disease. The positive clinical outcome suggests that nonimmunogenic tumors may be highly susceptible to immune effector cells generated by immunization.     

Cytochemical staining and flow cytometry methods applied to the diagnosis of acute leukemia in the pediatric population: an assessment of relative usefulness

BACKGROUND: Cytochemical staining has been used in the diagnosis of acute leukemia for more than 20 years. The general availability of flow cytometers and an extensive panel of antibody reagents useful for characterizing blood cell lineage question the usefulness of continuing routine use of the cytochemical staining for the diagnosis of acute leukemia. PATIENTS AND METHODS: Test results were evaluated in 122 (n = 122; 112 with acute lymphocytic leukemia and 10 with acute myeloid leukemia) patients selected from among 320 patients with acute leukemia at Texas Children's Hospital in 1997 and 1998. Results were selected for review if the clinical encounter represented the initial diagnostic work-up and if data were available from cytochemical staining and flow cytometry studies. RESULTS: Cell lineage classification derived from flow cytometry and cytochemical stains were in agreement in all cases. Definitive diagnoses were feasible using flow cytometry results alone in 120 of 122 patients (98.4%) as compared with only 99 of 122 patients (81.2%) when only cytochemical staining results were considered. In two patients with inconclusive flow cytometry results, cytochemical staining alone provided information sufficient for diagnosis. CONCLUSIONS: Results from this study indicate that with few exceptions, flow cytometry studies alone provide sufficient information for diagnosis and management of acute leukemia in children. Nevertheless, cytochemical staining should be available for those cases in which flow cytometry results fail to allow a definitive diagnosis. A modified testing protocol is recommended.