Surrogate markers for atherosclerosis in overweight subjects with atherogenic dyslipidemia: the GEMS project

Metabolic syndrome is a constellation of major risk factors for cardiovascular disease. In affected individuals with this syndrome, the independent contribution of low high-density lipoprotein-cholesterol and increased triglyceride levels to the development of atherosclerosis remains to be clarified. We assessed the relationship between these 2 parameters and several surrogate markers for atherosclerosis. One hundred and twenty overweight cases, defined as having high-density lipoprotein-cholesterol (or=75 percentile) were compared with 120 discordant overweight controls defined on lipid values (high-density lipoprotein-cholesterol >or=50 percentile and triglycerides 相似文献   

Ala54Thr polymorphism of the fatty acid binding protein 2 gene and saturated fat intake in relation to lipid levels and insulin resistance: the Coronary Artery Risk Development in Young Adults (CARDIA) study

The Thr54 allele of the intestinal fatty acid–binding protein Ala54Thr functional polymorphism (FABP2) is associated with increased fat oxidation and insulin resistance. We determined the cross-sectional associations of the FABP2 gene with lipid levels and insulin resistance in 2148 participants who completed the year-20 examination of the Coronary Artery Risk Development in Young Adults (CARDIA) study. No significant difference in total cholesterol, low-density or high-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol to total cholesterol ratio, or homeostasis model assessment of insulin resistance (HOMA-IR) was found between FABP2 genotypes. However, in the presence of a high–saturated fat diet (≥53.2 g/d, the 90th percentile for the population), the AA/AG genotypes (carriers of the Thr54 allele) of FABP2 had statistically significantly higher levels of log(HOMA-IR) (P = .006) and a lower high-density lipoprotein cholesterol to total cholesterol ratio (P = .03), and borderline statistically significantly higher levels of total cholesterol, low-density lipoprotein cholesterol, and log(triglycerides) (P values = .08, .07, and .05, respectively) compared with those with the GG genotype (Ala54 homozygotes). Lipid levels and log(HOMA-IR) did not vary by genotype with saturated fat intake less than 53.2 g/d. Limiting dietary saturated fat intake may be particularly important among carriers of the A allele of FABP2.     

Randomized controlled trial comparing outcomes of video capsule endoscopy with push enteroscopy in obscure gastrointestinal bleeding

BACKGROUND:

Optimal management of obscure gastrointestinal bleeding (OGIB) remains unclear.

OBJECTIVE:

To evaluate diagnostic yields and downstream clinical outcomes comparing video capsule endoscopy (VCE) with push enteroscopy (PE).

METHODS:

Patients with OGIB and negative esophagogastroduodenoscopies and colonoscopies were randomly assigned to VCE or PE and followed for 12 months. End points included diagnostic yield, acute or chronic bleeding, health resource utilization and crossovers.

RESULTS:

Data from 79 patients were analyzed (VCE n=40; PE n=39; 82.3% overt OGIB). VCE had greater diagnostic yield (72.5% versus 48.7%; P<0.05), especially in the distal small bowel (58% versus 13%; P<0.01). More VCE-identified lesions were rated possible or certain causes of bleeding (79.3% versus 35.0%; P<0.05). During follow-up, there were no differences in the rates of ongoing bleeding (acute [40.0% versus 38.5%; P not significant], chronic [32.5% versus 45.6%; P not significant]), nor in health resource utilization. Fewer VCE-first patients crossed over due to ongoing bleeding (22.5% versus 48.7%; P<0.05).

CONCLUSIONS:

A VCE-first approach had a significant diagnostic advantage over PE-first in patients with OGIB, especially with regard to detecting small bowel lesions, affecting clinical certainty and subsequent further small bowel investigations, with no subsequent differences in bleeding or resource utilization outcomes in follow-up. These findings question the clinical relevance of many of the discovered endoscopic lesions or the ability to treat most of these effectively over time. Improved prognostication of both patient characteristics and endoscopic lesion appearance with regard to bleeding behaviour, coupled with the impact of therapeutic deep enteroscopy, is now required using adapted, high-quality study methodologies.     

Partially covered self-expandable metal stents versus polyethylene stents for malignant biliary obstruction: A cost-effectiveness analysis

BACKGROUND/OBJECTIVE:

Partially covered self-expandable metal stents (SEMS) and polyethylene stents (PES) are both commonly used in the palliation of malignant biliary obstruction. Although SEMS are significantly more expensive, they are more efficacious than PES. Accordingly, a cost-effectiveness analysis was performed.

METHODS:

A cost-effectiveness analysis compared the approach of initial placement of PES versus SEMS for the study population. Patients with malignant biliary obstruction underwent an endoscopic retrograde cholangiopancreatography to insert the initial stent. If the insertion failed, a percutaneous transhepatic cholangiogram was performed. If stent occlusion occurred, a PES was inserted at repeat endoscopic retrograde cholangiopancreatography, either in an outpatient setting or after admission to hospital if cholangitis was present. A third-party payer perspective was adopted. Effectiveness was expressed as the likelihood of no occlusion over the one-year adopted time horizon. Probabilities were based on a contemporary randomized clinical trial, and costs were issued from national references. Deterministic and probabilistic sensitivity analyses were performed.

RESULTS:

A PES-first strategy was both more expensive and less efficacious than an SEMS-first approach. The mean per-patient costs were US$6,701 for initial SEMS and US$20,671 for initial PES, which were associated with effectiveness probabilities of 65.6% and 13.9%, respectively. Sensitivity analyses confirmed the robustness of these results.

CONCLUSION:

At the time of initial endoscopic drainage for patients with malignant biliary obstruction undergoing palliative stenting, an initial SEMS insertion approach was both more effective and less costly than a PES-first strategy.     

Systematic review of guidelines on peripheral artery disease screening

BackgroundPeripheral artery disease (PAD) screening may be performed to prevent progression of PAD or future cardiovascular disease in general. Recommendations for PAD screening have to be derived indirectly because no randomized trials comparing screening versus no screening have been performed. We performed a systematic review of guidelines to evaluate the value of PAD screening in asymptomatic adults.MethodsGuidelines in English published between January 1, 2003 and January 20, 2011 were retrieved using MEDLINE, CINAHL, the National Guideline Clearinghouse, the National Library for Health, the Canadian Medication Association Infobase, and the G-I-N International Guideline Library. Guidelines developed by national and international medical societies from Western countries, containing recommendations on PAD screening, were included. Two reviewers independently assessed rigor of guideline development using the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. One reviewer performed full extraction of recommendations, which was validated by a second reviewer.ResultsOf 2779 titles identified, 8 guidelines were included. AGREE scores varied from 33% to 81%. Five guidelines advocated PAD screening, others found insufficient evidence for PAD screening or were against it. Measurement of the ankle-brachial index (ABI) was generally recommended for middle-aged populations with elevated cardiovascular risk levels. Those identified as having PAD are reclassified as high risk, warranting intensive preventive interventions to reduce their risk of a cardiovascular event. The underlying evidence mainly consisted of studies performed in patients with established PAD. A meta-analysis that evaluated ABI testing in the context of traditional cardiovascular risk assessment was interpreted differently.ConclusionsRecommendations on PAD screening vary across current guidelines, making the value of PAD screening uncertain. The variation seems to reflect lack of studies that show added value of detection of early PAD beyond expectant management and traditional risk assessment.     

Sympathetic activation triggers endogenous opioid release and analgesia within peripheral inflamed tissue

Stress induces analgesia by mechanisms within and outside the brain. Here we show that the sympathetic nervous system is an essential trigger of intrinsic opioid analgesia within peripheral injured tissue. Noradrenaline, injected directly into inflamed hind paws of male Wistar rats, produced dose-dependent antinociception, reversible by alpha(1)-, alpha(2)- and beta(2)-antagonists. alpha(1)-, alpha(2)- and beta(2)-adrenergic receptors were demonstrated on beta-endorphin-containing immune cells and noradrenaline induced adrenergic receptor-specific release of beta-endorphin from immune cell suspensions. This antinociceptive effect of noradrenaline was reversed by micro - and delta-opioid antagonists as well as by anti-beta-endorphin. Stress-induced peripheral analgesia was abolished by chemical sympathectomy and by adrenergic antagonists. These findings indicate that sympathetic neuron-derived noradrenaline stimulates adrenergic receptors on inflammatory cells to release beta-endorphin, which induces analgesia via activation of peripheral opioid receptors.     

Inter-individual performance differences in younger and older adults differentially relate to amplitude modulations and phase stability of oscillations controlling working memory contents

Efficient encoding of relevant information and suppression of irrelevant information influence working memory (WM) performance, which is limited and declines in adulthood. A cued Sternberg WM task and electroencephalographic recordings (EEG) were used to investigate encoding and control operations in response to to-be-remembered (REM) and not-to-be-remembered (NREM) stimuli in younger and older adults. Younger and older adults selectively remembered REM items in a final recognition memory test. During early stages of stimulus processing, inter-trial phase stability was higher for REM than for NREM items in younger and older adults, presumably reflecting preferential encoding of REM items. At later stages, the oscillatory power of oscillations in the alpha/beta frequency range was higher for NREM than for REM, presumably reflecting the inhibitory top-down suppression of task-irrelevant information. Early phase stability was selectively related to working memory performance in younger adults and high-functioning older adults. The results of this study reveal the differential contributions of low-level feature binding and strategic control components to adult age differences in WM, and show that older adults with more youth-like processing dynamics tend to achieve higher levels of performance.     

Thiotepa‐based conditioning versus total body irradiation as myeloablative conditioning prior to allogeneic stem cell transplantation for acute lymphoblastic leukemia: A matched‐pair analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

The optimal conditioning regimen to employ before hematopoietic stem cell transplantation in acute lymphoblastic leukemia (ALL) is still undecided, and while cyclophosphamide/total body irradiation (Cy/TBI) is the most commonly used myeloablative regimen, there are concerns regarding long‐term toxicity for patients conditioned with this regimen. Thiotepa‐based conditioning is an emerging radiation‐free regimen with recent publications indicative of comparable clinical outcomes to TBI‐based conditioning. In this analysis of the acute leukemia working party of the EBMT, we performed a retrospective matched‐pair analysis, evaluating the outcome of adult patients with ALL who received thiotepa‐based conditioning (n = 180) with those receiving Cy/TBI conditioning (n = 540). The 2‐year leukemia‐free survival and overall survival (OS) rates of both conditioning regimens were comparable, 33% for thiotepa [95% confidence interval (CI): 26.4‐42.8] versus 39% for Cy/TBI (95% CI: 34.8‐44.5] (P = .33) and 46.5% [95% CI: 38.6‐56.1] versus 48.8% [95% CI: 44.2‐54] (P = .9), respectively. There was no significant difference between the two regimens in the incidence of either acute graft versus host disease (GVHD) or chronic GVHD. Multivariate analysis demonstrated increased relapse incidence for thiotepa conditioning compared to Cy/TBI (HR = 1.78, 95% CI, 1.07‐2.95; P = .03) which did not affect OS. Our results indicate that thiotepa‐based conditioning may not be inferior to Cy/TBI for adult patients with ALL.     

Purification and partial characterization of a 32-kilodalton sialic acid-specific lectin from Aspergillus fumigatus

Adherence of the opportunistic fungus Aspergillus fumigatus to the extracellular matrix components is considered a crucial step in the establishment of the infection. Given the high carbohydrate content of these glycoproteins and the role of carbohydrate-protein interactions in numerous adherence processes, the presence of a lectin in A. fumigatus was investigated. Different fungal extracts obtained by sonication or grinding in liquid nitrogen from resting or swollen conidia, as well as from germ tubes and mycelium, were tested by hemagglutination assays using rabbit erythrocytes. A lectin activity was recovered in all the extracts tested. However, sonication of resting conidia resulted in the highest specific activity. Purification of the lectin was achieved by gel filtration followed by ion-exchange and hydrophobic-interaction chromatographies. Analysis of the purified lectin by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed an apparent molecular mass of 32 kDa, which is similar to that of the alkaline protease already identified from different strains of A. fumigatus. However, as evidenced by the use of an alkaline protease-deficient mutant, the two activities were supported by distinct proteins. In addition, hemagglutination inhibition experiments using different saccharides and glycoproteins demonstrated the specificity of the lectin for sialic acid residues. Together these results suggest that this lectin may contribute to the attachment of conidia to the extracellular matrix components through the recognition of the numerous terminal sialic acid residues of their carbohydrate chains.