Detecting hippocampal hypometabolism in Mild Cognitive Impairment using automatic voxel-based approaches

While the hippocampus is constantly reported as the site of earliest and highest structural alteration in Alzheimer's disease (AD), findings regarding the metabolic status of this region are rather heterogeneous. It has been proposed that only a time-consuming individual region-of-interest (ROI) approach would allow the detection of hypometabolism in this complex and small area. Our main goal with this study is to assess whether more automatic and clinically useful methods would be sensitive enough when considering other methodological confounds. From a single PET data set collected in 28 patients with amnestic Mild Cognitive Impairment (aMCI) and 19 controls, we assessed the effects of partial volume effect (PVE) correction, scaling (using vermis or global means), and analysis method (individual ROI versus more automatic template-based ROI or voxel-based approaches) on hippocampal hypometabolism detection in aMCI. PVE correction and scaling both showed a significant effect on group comparison, while the analysis method (individual versus template-based ROI) surprisingly did not. Hippocampal metabolic decrease was significant in all vermis-scaled conditions, and more so after PVE correction. Our findings highlight the crucial relevance of using reference-region-based (instead of global) scaling, and the higher sensitivity of PVE-corrected PET measures, to detect hippocampal hypometabolism in aMCI. They also show that hippocampal metabolic decline can be detected using template-based ROI as well as voxel-based methods. These findings have clinical relevance since they support the validity of more automatic and time-saving approaches to assess hippocampal metabolism changes in aMCI and early AD.     

Disease progression in macaques with low SIV replication levels: on the relevance of TREC counts

BACKGROUND: An attenuated immunodeficiency virus has been long considered innocuous. Nevertheless, converging data suggest that low levels of viral replication can still provoke AIDS. Pathogenesis of these attenuated infections is not understood. OBJECTIVES: To determine the pathogenicity of a long-term attenuated infection and to delineate T-cell dynamics during such an infection. METHODS: This is a cross-sectional study of 12 rhesus macaques infected with SIV Delta nef for 8 years. We evaluated apoptosis (annexin V), activation (HLA-DR, Ki67), and newly generated T cells (TCR excision circle: TREC). RESULTS: Infection with SIV Delta nef induced pathological CD4 T-cell depletion after 8 years of infection. Virus replication and CD8 T-cell activation positively correlated with the rate of disease progression. The frequency of TREC within CD8+CD45RA+ cells increased in SIV Delta nef-infected animals compared to age-matched non-infected controls. Moreover, in the cohort of infected animals, TREC+CD45RA+CD4+ T-cell counts correlated strongly with non-progression to AIDS. The animal with the lowest rate of disease progression exhibited a 115-fold increase in TREC+CD45RA+CD4+ T-cell counts compared to age-matched non-infected controls. In contrast, the animal showing the fastest rate of progression to AIDS displayed 600-fold lower TREC+CD45RA+CD4+ T-cell counts compared to age-matched non-infected controls. CONCLUSIONS: Our results suggest that the thymus plays a major role in the pathogenesis of an attenuated SIV infection and that a sustained thymic output could maintain CD4 T-cell homeostasis in the context of low viral loads.     

Single-Molecule hsTnI and Short-Term Risk in Stable Patients With Chest Pain

Background

Evaluation of stable symptomatic outpatients with suspected coronary artery disease (CAD) may be challenging because they have a wide range of cardiovascular risk. The role of troponin testing to assist clinical decision making in this setting is unexplored.

Variations in Digestive Physiology of Rats After Short Duration Flights Aboard the US Space Shuttle

The purpose of this work was to assess the influence of microgravity on several endogenous and microbial parameters of digestive physiology. On the occasion of two Spacelab Life Sciences missions, SLS-1 (a 9-day space flight) and SLS-2 (a 14-day space flight), Sprague-Dawley rats flown aboard the US space shuttle were compared to age-matched ground-based controls. In both flights, exposure to microgravity modified cecal fermentation: concentration and profile of short-chain fatty acids were altered, whereas urea and ammonia remained unchanged. Only in SLS-1 was there an induction of intestinal glutathione-S-transferase. Additional analyses in SLS-2 showed a decrease of hepatic CYP450 and of colonic goblet cells containing neutral mucin. After a postflight recovery period equal to the mission length, only modifications of the hepatic and intestinal xenobiotic metabolizing enzymes still persisted. These findings should help to predict the alterations of digestive physiology and detoxification potential likely to occur in astronauts. Their possible influence on health is discussed.     

Calcium-sensing receptor autoantibodies are relevant markers of acquired hypoparathyroidism

We investigated the presence of autoantibodies (aAbs) directed against the parathyroid gland in 17 patients with spontaneous isolated acquired hypoparathyroidism. Fourteen patients with acquired hypoparathyroidism (AH) associated with type I or II autoimmune polyendocrinopathy syndrome were also tested in comparison with a control group of 68 subjects without AH, including patients with other autoimmune diseases and healthy blood donors. aAbs against parathyroid tissue were screened using an indirect immunofluorescence technique on primate parathyroid tissue and human parathyroid adenoma. aAbs against the calcium-sensing receptor (CaSR) were analyzed using an immunoblotting assay with the recombinant extracellular domain of the human CaSR as antigen. Seven of the 31 patients with AH were positive for CaSR aAbs. Five of the positive sera were obtained from the group with isolated AH. The two other positive sera were from patients with autoimmune polyendocrinopathy syndrome. The sensitivity of the immunoblotting technique was higher than that of both the radioimmunological test using the extracellular domain of the CaSR and the indirect immunofluorescence technique. There were no positive sera in the control group. In conclusion, using an immunoblotting assay, we demonstrate the presence of CaSR aAbs in about one third of the patients with isolated AH, pointing out the value of detecting such aAbs to assess the autoimmune origin of the disease.     

Design features of the Avasimibe and Progression of coronary Lesions assessed by intravascular UltraSound (A-PLUS) clinical trial

Background Although statins have been shown to be beneficial in the management of hyperlipidemia and the reduction of cardiovascular morbidity and mortality, rates of major cardiovascular events remain high despite their use. Inhibition of the acyl coenzyme A: cholesterol acyltransferase (ACAT) enzyme in the arterial wall may prevent excess accumulation of cholesteryl esters in macrophages. In addition to ACAT inhibitor monotherapy, combination of a statin with an ACAT inhibitor may be a promising approach to further prevent the progression of atherosclerosis. Methods This report describes the design and methodologic features of a double-blind, randomized, placebo-controlled trial to assess the effect of the ACAT inhibitor avasimibe at 50-, 250-, and 750-mg daily dosages on the progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS). All patients receive background lipid-lowering therapy when necessary. The study population consists of patients with at least one 20% to 50% diameter stenosis in a coronary artery with a reference diameter of ≥2.5 mm. IVUS and coronary angiography are performed at baseline and repeated at 24 months. The primary study end point is the change from baseline in plaque volume in a 30-mm segment of the coronary artery assessed by 3-dimensional IVUS. Several other IVUS and angiographic end points are measured. Conclusions The Avasimibe and Progression of coronary Lesions assessed by intravascular UltraSound (A-PLUS) trial is among the first large imaging trials to use IVUS as a primary end point and assesses the effects of the ACAT inhibitor avasimibe on atherosclerosis progression. (Am Heart J 2002;144:589-96.)