Health utilities in Alzheimer's disease: a cross-sectional study of patients and caregivers.

OBJECTIVES: Although the broad impacts of Alzheimer's disease (AD) are increasingly recognized, little work has focused on the overall health-related quality of life experienced by Alzheimer's disease patients and their caregivers. The study had two main objectives: (1) to test the feasibility of measuring health utilities in Alzheimer's disease with a generic preference-weighted instrument using proxy respondents and (2) to assess the utility scores of Alzheimer's disease patients (and their caregivers) in different disease stages and care setting. METHODS: A cross-sectional study of 679 Alzheimer's disease patient/caregiver pairs was conducted at 13 sites in the United States: four academic medical centers, four managed care plans, two assisted living facilities, and three nursing homes. The Health Utilities Index Mark II (HUI:2) questionnaire was administered to caregivers of patients who responded both as proxies for patients and for themselves. Responses to the questionnaire were converted into a global utility score, between 0 and 1, using the HUI:2 multi-attribute utility function. RESULTS: Global utility scores varied considerably across patients' Alzheimer's disease stage: for the six stages assessed (questionable, mild, moderate, severe, profound, and terminal), mean utility scores were 0.73, 0.69, 0.53, 0.38, 0.27, and 0.14, respectively. In multiple regression analyses, Alzheimer's disease stage was a negative and significant predictor of utility scores for patients; setting did not exert an independent effect. Utility scores for the caregivers were insensitive to patients' Alzheimer's disease stage and setting. CONCLUSIONS: Patients' Alzheimer's disease stage had a substantial influence on health utilities, as measured by the HUI:2. More research is needed to assess the validity of using proxy respondents.     

Risk of bacterial infection associated with allogeneic blood transfusion among patients undergoing hip fracture repair

BACKGROUND: The relationship between allogeneic blood transfusion and bacterial infection remains uncertain. An increased risk of bacterial infection would represent the most important risk of allogeneic transfusion, because viral disease transmission has become so rare. STUDY DESIGN AND METHODS: A retrospective cohort study of 9598 consecutive hip fracture patients at least 60 years old who underwent surgical repair was performed. The primary outcome was serious bacterial infection, defined as bacteremia, pneumonia, deep wound infection, or septic arthritis or osteomyelitis. Secondary outcomes included two individual infections, pneumonia and urinary tract infection (UTI), and the cost of infection. Hospital cost of infection was assessed by linking the study population to Medicare data. RESULTS: Fifty-eight percent of patients received at least one transfusion. Serious bacterial infection occurred in 437 patients (4.6%); 28.8 percent of this group died during the hospital stay. Pneumonia occurred in 361 patients (3.8%) and UTI occurred in 1157 patients (12.1%). The adjusted risk of serious bacterial infection associated with transfusion was 1.35 (95% CI, 1.10-1.66). The adjusted risk for pneumonia was 1.52 (95% CI, 1.21-1.91), and that for UTI was 1.03 (95% CI, 0.91-1.17). A dose-response relationship was present for serious bacterial infection (p = 0.001) and pneumonia (p = 0.001). The cost of hospitalization was $14,000 greater for patients with serious infection than for patients without infection. CONCLUSION: Blood transfusion is associated with a 35-percent greater risk of serious bacterial infection and a 52-percent greater risk of pneumonia. Postoperative infections are costly. The risk of bacterial infection may be the most common life-threatening adverse effect of allogeneic blood transfusion.     

Left ventricular function during interval and steady state exercise.

PURPOSE: Interval training (INT) is a commonly used method of exercise training in both athletic and clinical populations. Although we generally understand left ventricular (LV) function during steady state (SS) exercise, there are no data regarding LV function during INT. METHODS: We studied eight healthy, physically active volunteers during upright cycle ergometry during 15 min of both SS and INT, at the same average power output (90% individual anaerobic threshold), using first pass radionuclide ventriculography. During INT (60s/60s), measures of LV function were made during work (220 W) after 4 and 12 min and during recovery (120 W) after 7 and 15 min. These were compared with the average of four temporally matched measures made during SS (170 W). RESULTS: During INT, LV ejection fraction increased from rest (67 +/- 6%) to 77 +/- 5, 80 +/- 5, 77 +/- 5 and 79 +/- 4% after 4, 7, 12, and 15 min, respectively. During SS, LV ejection fraction was not significantly different at rest (70 +/- 4%) or during exercise (76 +/- 4, 79 +/- 4, 80 +/- 3, and 81 +/- 3%) after 4, 7, 12, and 15 min, respectively. Other measures of LV function (HR, BP, LV volumes, cardiac output, systemic vascular resistance, peak emptying, and filling rates) were likewise similar during temporally matched measurements during INT and SS. CONCLUSIONS: Although there were the expected transitions of ejection fraction with work and recovery, the overall hemodynamic picture during INT was very similar to SS. These data suggest that LV function during INT is not substantially different to that during SS.     

Transient MRI-detected water apparent diffusion coefficient reduction correlates with c-fos mRNA but not hsp70 mRNA induction during focal cerebral ischemia in rats

Cerebral ischemia induces immediate early genes such as c-fos and stress genes such as hsp70. In this study, the spatial relationships between c-fos and hsp70 mRNA expression and changes detectable with diffusion and perfusion magnetic resonance (MR) imaging were examined. The middle cerebral artery (MCA) of young adult rats was occluded for 30 or 60 min. Diffusion MR (D-MR) images were acquired continuously during the ischemic period and dysprosium-contrast perfusion (P-MR) images were acquired at the end of the ischemic period. C-fos and hsp70 mRNA expression were examined with in situ hybridization. The most significant finding of this work was that for both durations of ischemia, c-fos induction was observed in cortical and sub-cortical regions exhibiting a transient reduction in the apparent diffusion coefficient of water (ADC). Transients which occurred on a time scale of 3 min may have been caused by spreading depression. Those occurring on a 10-min time scale may have been caused by an initial reduction in blood flow with occlusion that was followed by an ischemia-induced increase in collateral blood flow. P-MR imaging showed that perfusion in c-fos positive regions was higher than in regions with persistently reduced ADC. Hsp70 induction did not correlate with transient ADC reduction. It was induced in the MCA territory in regions showing persistent ADC changes, with induction being greatest at the periphery of these regions. It was also induced in regions that exhibited both spontaneous reversal of the diffusion changes and decreased perfusion.     

A simple permutation‐based test of intermodal correspondence

Many key findings in neuroimaging studies involve similarities between brain maps, but statistical methods used to measure these findings have varied. Current state‐of‐the‐art methods involve comparing observed group‐level brain maps (after averaging intensities at each image location across multiple subjects) against spatial null models of these group‐level maps. However, these methods typically make strong and potentially unrealistic statistical assumptions, such as covariance stationarity. To address these issues, in this article we propose using subject‐level data and a classical permutation testing framework to test and assess similarities between brain maps. Our method is comparable to traditional permutation tests in that it involves randomly permuting subjects to generate a null distribution of intermodal correspondence statistics, which we compare to an observed statistic to estimate a p‐value. We apply and compare our method in simulated and real neuroimaging data from the Philadelphia Neurodevelopmental Cohort. We show that our method performs well for detecting relationships between modalities known to be strongly related (cortical thickness and sulcal depth), and it is conservative when an association would not be expected (cortical thickness and activation on the n‐back working memory task). Notably, our method is the most flexible and reliable for localizing intermodal relationships within subregions of the brain and allows for generalizable statistical inference.     

Mechanism of tumor promoter inhibition of cellular binding of epidermal growth factor

In previous studies we demonstrated that the tumor-promoting agent 12-O-tetradecanoyl phorbol 13-acetate (TPA) and related macrocyclic diterpenes are potent inhibitors of the binding of epidermal growth factor (EGF) to its cell surface receptors in HeLa cells. The present study explores the specificity and mechanism of this effect. We have found that the same effect is observed in various cell types derived from mice, rats, or humans. In HeLa cells TPA inhibits the initial binding of EGF and also accelerates the loss of previously bound EGF from cells. The released EGF is recovered largely intact in the medium, indicating that TPA does not induce increased proteolysis or increased cellular internalization and degradation of EGF. The TPA effect on EGF receptors is mediated by a highly temperature-dependent process because TPA inhibition of EGF binding, and TPA-induced release of prebound EGF, are much greater at 37 degrees C or 22 degrees C than at 4 degrees C. A curious feature is that when cells are grown in TPA for one or more days they escape or become refractory to TPA inhibition of EGF binding. Taken together, these results suggest that TPA inhibits EGF binding not by binding directly to the "active site" of the EGF receptor but by indirectly altering the conformation or inducing the clustering of EGF receptors. These and other membrane effects of this tumor promoter suggest that it is a valuable probe for elucidating complex aspects of membrane structure and function.     

2000～2010:骨关节十年

这篇译文的原稿是今年 3月份在全美骨科年会开幕式上宣读的一份纲领性文件 ,并在美国版和英国版的《TheJournalofBoneandJointSurgery》杂志上予以登摘。骨关节十年是一次全球范围内的运动 ,对我国骨科学今后 10年的发展方向必将产生重大的影响。本文按照《TheJournalofBoneandJointSurgery》美国版的原文进行了翻译 ,希望能使更多骨科界的同道尽快了解“骨关节十年”运动的内容和形式 ,并积极参与。     

Mild hypothermia decreases the incidence of transient ADC reduction detected with diffusion MRI and expression of c-fos and hsp70 mRNA during acute focal ischemia in rats

The effects of mild hypothermia on the apparent diffusion coefficient of water (ADC) and expression of c-fos and hsp70 mRNA were examined during acute focal cerebral ischemia. Young adult rats were subjected to 60-min middle cerebral artery occlusion under either normothermia (37.5°C) or hypothermia (33°C). Diffusion-weighted echo-planar magnetic resonance imaging was used to monitor changes in ADC throughout the ischemic period. Perfusion MRI with dysprosium contrast was used at the end of the ischemic period to verify that the occlusion was successful. C-fos and hsp70 mRNA expression were examined with in situ hybridization at the end of the ischemic period. The results indicate that the size of the region that exhibited reduced ADC was smaller during hypothermia than during normothermia. Hypothermia also decreased the frequency of occurrence of transient ADC reductions, especially in dorsal aspects of cortex. Expression of both c-fos and hsp70 mRNA were markedly reduced by hypothermia. Transient ADC reduction and c-fos expression are associated with spreading depression, which is believed to contribute to lesion expansion during acute focal ischemia. The results suggest that part of the neuroprotective effect of hypothermia may be due to a reduced incidence of spreading depression.     

Study of Spectrally Resolved Thermoluminescence in Tsarev and Chelyabinsk Chondrites with a Versatile High-Sensitive Setup

Thermoluminescence (TL) research provides a powerful tool for characterizing radiation-induced processes in extraterrestrial matter. One of the challenges in studying the spectral features of the natural TL of stony meteorites is its weak intensity. The present work showcases the capabilities of a high-sensitive original module for measuring the spectrally resolved TL characteristics of the Chelyabinsk and Tsarev chondrites. We have analyzed the emission spectra and glow curves of natural and induced TL over the 300–650 nm and RT–873 K ranges. A quasi-continuous distribution of traps active within the 350–650 K range was found in the silicate substructure of both meteorites under study. Based on the general order kinetic formalism and using the natural TL data, we also estimated the activation energies of E_A = 0.86 and 1.08 eV for the Chelyabinsk and Tsarev chondrites, respectively.