Validity and reproducibility of a food frequency questionnaire by cognition in an older biracial sample

It is not currently known how dietary assessment in older persons is affected by cognition. In a 1997-2000 study, the authors assessed the validity and reproducibility of a modified Harvard self-administered food frequency questionnaire (SFFQ) among 118 Black and 114 White randomly selected participants, aged 68-99 years, of the Chicago Health and Aging Project. Participants completed multiple 24-hour dietary recall interviews (mean=3.6) over 12 months and two SFFQs in the first and 12th months. The average energy-adjusted intraclass correlation coefficient for 15 nutrients was 0.59 for 1-year reproducibility in nutrient intake levels assessed by the SFFQ. The average energy-adjusted Pearson correlation coefficient was 0.46 for comparative validity between nutrient intake levels on the SFFQ and the dietary recalls. SFFQ reproducibility was higher among men, and comparative validity with the dietary recalls was higher among women. There were no remarkable differences in the correlations by age, race, educational level, presence of chronic conditions, or cognitive ability. The modified Harvard SFFQ is a reasonable method of dietary assessment even in a population of older persons, some of whom are at advanced age, have chronic health conditions, and have cognitive impairment.     

IL-10 has a protective role in experimental autoimmune uveoretinitis

The role of IL-10 in the regulation of ocular autoimmune disease was studied in experimental autoimmune uveoretinitis (EAU) elicited in mice by immunization with the retinal antigen interphotoreceptor retinoid binding protein. IL-10-deficient mice were susceptible to EAU, indicating that pathogenesis can occur without presence of IL-10. Treatment of normal mice with IL-10 for 5 days after uveitogenic immunization ameliorated subsequent EAU scores, and down-regulated antigen-specific production of tumor necrosis factor-alpha and IFN- gamma. A concomitant treatment with IL-4 further reduced disease, and resulted in emergence of antigen-specific IL-4 and IL-10 production, as well as in enhancement of the IgG1 antibody isotype. IL-4 by itself was not protective. Only IL-10, but not IL-4, was able to inhibit the function of differentiated uveitogenic T cells in culture. Expression of mRNA for Th1 and Th2 cytokines in the eye during the course of EAU showed that while a Th1 pattern predominated early, IL-10 mRNA expression coincided with down-regulation of the Th1 response and resolution of EAU. Systemic neutralization of IL-10 during the expression phase of EAU resulted in elevated disease scores. Our results suggest that endogenous IL-10 limits expression of EAU and may play a role in the natural resolution of disease. The data further suggest that exogenous IL-10 may be useful in therapeutic control of autoimmune uveitis. While IL-10 by itself is sufficient to suppress Th1 effector development and function, a concomitant administration of IL-4 is required to shift the autoimmune response towards a non-pathogenic Th2 pathway.      

Purified CD34+ Lin- Thy+ stem cells do not contain clonal myeloma cells

High-dose therapy with autologous marrow or peripheral blood stem cell (PBSC) rescue has been extensively applied in the treatment of multiple myeloma (MM) patients during the past 10 years resulting in improved event-free and overall survival when compared with standard chemotherapy. However, relapses are common and cure is unlikely in the majority of patients. Because both bone marrow and PBSCs are contaminated with myeloma cells it is conceivable that relapse after autotransplantation originates at least in part from autografted tumor cells. In this study, mobilized PBSCs were examined for the presence of myeloma cells based on immunophenotyping and sensitive polymerase chain reaction (PCR)-based techniques. In addition, CD34+ Lin- Thy+ stem cells were purified from mobilized PBSC harvests of 10 MM patients by sequentially using counterflow elutriation centrifugation, treatment with phenylalanine methylester, and flow sorting, using 5-parameter gating (propidium iodide, forward scatter, side scatter, CD34+ v Lin- and CD34+ v Thy+). Virtually all mobilized unsorted PBSC preparations contained myeloma cells in sufficient quantities (range, < 0.01 to > 10%) potentially causing a disease relapse. Stem cell purification led to an overall enrichment by about 50-fold in all 10 patients; approximately 90% of the final cell population expressed CD34+ Lin- Thy+ with no evidence of myeloma cell contamination based on flow cytometric analysis of CD38bright cells (< 0.1%). Quantitative PCR amplification of patient-specific complementarity determining region III (CDRIII) DNA sequences showed depletion of clonal B cells by 2.7 to 7.3 logs, with the highest log reduction noted in the samples initially containing the most tumor cells. Our results show that purification of CD34+ Lin- Thy+ cells depletes myeloma cells to undetectable levels from up to 10% present in unsorted PBSCs, thus offering a tool to investigate whether MM relapse after autotransplantation can be reduced markedly.     

Atheroablation with the Kensey catheter: a pathologic study

The mode of action of the Kensey catheter, a new atheroablation device, was investigated. Fresh above-the-knee amputated legs were used for recanalization of the superficial femoral artery. The variables used were identical to those of clinical trials, including a rotational speed of 50,000 rpm and an injection rate of 40 mL/min. The debris produced by the catheter was studied cytologically, and the arterial segments were examined histologically. The particle size in the debris ranged from 1 to 2,000 microns. The softer plaques produced a fine fibrin dust background with long strips of intima ranging from 10 to 2,000 microns. Complicated calcified plaques produced larger background material (10-120 microns) but smaller strips of intima (50-800 microns). Dissections and perforations occurred. Some of the debris produced by the atheroablation process was used to embolize a canine heart and kidney. Small focal infarctions were found in the heart, and large and multiple infarcts were seen in the kidney. In clinical studies the debris appears to be tolerated in the lower extremities. Its safety in the kidney and heart are questioned.     

Expansion in vitro of retrovirally marked totipotent hematopoietic stem cells

A large number of biologic, technological, and clinical studies await the development of procedures that will allow totipotent hematopoietic stem cells to be expanded in vitro. Previous work has suggested that hematopoiesis can be reconstituted using transplants of cells from long- term marrow cultures. We have used retrovirus mediated gene transfer to demonstrate that marked totipotent hematopoietic stem cells are both maintained and can be amplified in such cultures, and then subsequently regenerate and sustain lympho-myeloid hematopoiesis in irradiated recipients. Marrow cells from 5-fluorouracil-treated male mice were infected with a recombinant virus carrying the neomycin resistence gene and seeded onto irradiated adherent layers of pre-established, long- term marrow cultures of female origin. At 4 weeks, cells from individual cultures were transplanted into single or multiple female recipients. Southern blot analysis of hematopoietic tissue 45 days posttransplantation showed retrovirally marked clones common to lymphoid and myeloid tissues in 14 of 23 mice examined. Strikingly, for 3 of 4 long-term cultures, multiple recipients of cells from a single flask showed marrow and thymus repopulation with the same unique retrovirally marked clone. These results establish the feasibility of retroviral-marking techniques to demonstrate the maintenance of totipotent lympho-myeloid stem cells for at least 4 weeks in the long- term marrow culture system and provide the first evidence of their proliferation in vitro. Therefore, such cultures may serve as a starting point for identifying factors that stimulate totipotent hematopoietic stem cell expansion.     

Intra- and interindividual variation in measurements of beta-carotene, retinol, and tocopherols in diet and plasma

Twenty-four men were studied for 4 wk to estimate intra- and interindividual variation of retinol, beta-carotene, and tocopherols in diet and plasma. Ratios of intra- to interindividual variances ranged from 0.62 for beta-carotene in plasma to 6.02 for vitamin E in diet. Results indicate that 3-9 independent measurements may be required to distinguish reliably even large differences (approximately 1 SD) in these micronutrients; 28-86 independent measurements may be needed for small differences (approximately 0.25 SD). If uncontrolled, large ratios of intra- to interindividual variance can constitute an important source of error in studies of micronutrients.     

Variability in fibrinogen measurements: an obstacle to cardiovascular risk stratification.

The clinical utility of fibrinogen measurement has been limited by large intraindividual variability. Several approaches that have been shown to improve the repeatability of fibrinogen include acquisition of samples at the same time of day, standardized sample procurement techniques, and multiple replicate sampling. This study employed established pre-analytical and analytical techniques known to reduce fibrinogen variability, including the acquisition of three replicate samples, each analyzed in duplicate, to evaluate the impact of intraindividual variability in fibrinogen measurement at baseline and 3 months on cardiovascular risk in 60 healthy subjects. Classification accuracy was evaluated by the ability to categorize subjects into tertiles of fibrinogen. Only 55% (33/60) of the subjects were correctly assigned to the appropriate fibrinogen tertile. Fibrinogen measurements varied by more than 10% in 45% of subjects and by 5% in 80% of subjects. Intraindividual variability in fibrinogen measurement with a functional assay limits cardiovascular risk assessment even when three replicates are averaged.