125 research outputs found

    Carotid endarterectomy impairs blood pressure homeostasis by reducing the physiologic baroreflex reserve

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    ObjectiveTo assess the impact of carotid endarterectomy on blood pressure homeostasis and baroreflex function, with particular reference to the presence or absence of significant contralateral carotid artery disease, we conducted a prospective study in 80 patients with symptomatic extracranial carotid disease undergoing carotid endarterectomy in a regional teaching hospital over 2 years.MethodsPatients were divided into two groups: the control group (n = 37) had no significant contralateral carotid disease; patients in the diseased group (n = 23) had either >70% stenosis or occlusion of the contralateral carotid artery. Seventeen patients with abnormal heart rhythms, poor quality recordings, or with intermediate degrees of contralateral carotid stenosis were excluded. Three patients who had previously undergone contralateral carotid endarterectomy were separately evaluated. Atheromatous plaque was removed from carotid lumen and the baroreflex mechanism received direct intraoperative stimulation before and after carotid endarterectomy. The main outcome measures were (1) the hemodynamic response to the carotid endarterectomy, baroreflex sensitivity, and operating set point (the resting blood pressure, which the baroreflex mechanism maintains) before and after removal of the atheromatous plaque, and (2) the responsiveness of the ipsilateral baroreceptor mechanism to direct stimulation. The impact of the presence of contralateral carotid stenosis on these variables was also evaluated.ResultsPatients in the two groups were comparable for preoperative demographic, medication, and hemodynamic variables. Carotid endarterectomy led to a rise in mean arterial pressure from 81.3 ± 3.9 mm Hg to 103.5 ± 4.6 mm Hg (P < .00001) and from 87.6 ± 4.3 mm Hg to 94.0 ± 4.5 mm Hg (P < .003) in the diseased and control groups, respectively. The magnitude of blood pressure response was significantly greater in the diseased group than in the control group (P < .00001). This hypertensive shift was not accompanied by the expected fall in heart rate. Direct baroreflex stimulation prior to carotid endarterectomy caused a significantly greater response in the diseased group, suggesting sensitization of the ipsilateral carotid baroreceptor in the presence of contralateral carotid disease. Furthermore, the baroreflex response was obliterated after endarterectomy. There were significant reductions in baroreflex sensitivity and a hypertensive shift in the operating set point, the magnitude of which was significantly greater in patients with contralateral carotid disease.ConclusionsCarotid endarterectomy impairs blood pressure homeostasis through surgical destruction of the ipsilateral carotid baroreflex mechanism. Patients with contralateral carotid stenosis have a reduced baroreflex reserve and show greater baroreflex dysfunction and hemodynamic instability after endarterectomy. These patients are at greater risk of postendarterectomy complications and should be monitored closely

    Role of blood cells dynamism on hemostatic complications in low-risk patients with essential thrombocythemia

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    Patients with essential thrombocythemia (ET) aged less than 60 years, who have not suffered a previous vascular event (low-risk patients), may develop thrombotic or hemorrhagic events. So far, it has not been possible to identify useful markers capable of predicting which of these patients are more likely to develop an event and therefore who needs to be treated. In the present study, we analysed the relationship between vascular complications and longitudinal blood counts of 136 low-risk ET patients taken over a sustained period of time (blood cells dynamism). After a median follow-up of 60 months, 45 out of 136 patients (33%) suffered 40 major thrombotic and 5 severe hemorrhagic complications. A total number of 5,781 blood counts were collected longitudinally. Thrombotic and hemorrhagic events were studied together (primary endpoint) but also separately (thrombotic alone = secondary endpoint; hemorrhagic alone = tertiary endpoint). The primary endpoint showed no significant association between platelet and WBC count at diagnosis and risk of any event (platelet, p = 0.797; WBC, p = 0.178), while Hb at baseline did show an association (p = 0.024). In the dynamic analysis with Cox regression model, where the blood count values were studied by time of follow-up, we observed that the risk for Hb was 1.49 (95% CI 1.13-1.97) for every increase of 1 g/dL, and that this risk then marginally decreased during follow-up. WBC was associated with an increased risk at baseline for every increase of 1 7 10(9)/L (hazard ratio (HR) 1.07, 95% CI 1.01-1.13, p = 0.034), the risk was stable during follow-up (HR 0.95, p = 0.187 at 60 months). Also, for each increment at baseline of 100 7 10(9) platelets/L, HR was increased by 1.08 (95% CI 0.97-1.22, p = 0.159) and decreases during follow-up. In conclusion, this study is the first to evaluate in ET low-risk patients, the risk of developing a thrombotic/hemorrhagic event considering blood counts over time. Overall our study shows that the risk changes over time. For example, the risk associated with WCC is not linear as previously reported. An interesting new finding is that PLT and even Hb contribute to the risk of developing vascular events. Future treatments should take into consideration these findings and aim to control all parameters over time. We believe this early study may help develop a dynamic analysis model to predict thrombosis in the single patient. Further studies are now warranted to further validate our findings

    "Galileo Galilei" (GG) a small satellite to test the equivalence principle of Galileo, Newton and Einstein

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    "Galileo Galilei" (GG) is a small satellite designed to fly in low Earth orbit with the goal of testing the Equivalence Principle-which is at the basis of the General Theory of Relativity-to 1 part in 1017. If successful, it would improve current laboratory results by 4 orders of magnitude. A confirmation would strongly constrain theories; proof of violation is believed to lead to a scientific revolution. The experiment design allows it to be carried out at ambient temperature inside a small 1-axis stabilized satellite (250 kg total mass). GG is under investigation at Phase A-2 level by ASI (Agenzia Spaziale Italiana) at Thales Alenia Space in Torino, while a laboratory prototype (known as GGG) is operational at INFN laboratories in Pisa, supported by INFN (Istituto Nazionale di fisica Nucleare) and ASI. A final study report will be published in 2009

    Factors Affecting the Decision to Initiate Anticoagulation After Spine Surgery: Findings From the AOSpine Anticoagulation Global Initiative

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    STUDY DESIGN: Cross-sectional, international survey. OBJECTIVES: To identify factors influencing pharmacologic anticoagulation initiation after spine surgery based on the AOSpine Anticoagulation Global Survey. METHODS: This survey was distributed to the international membership of AOSpine (n = 3805). A Likert-type scale described grade practice-specific factors on a scale from low (1) to high (5) importance, and patient-specific factors a scale from low (0) to high (3) importance. Analysis was performed to determine which factors were significant in the decision making surrounding the initiation of pharmacologic anticoagulation. RESULTS: A total of 316 spine surgeons from 64 countries completed the survey. In terms of practice-specific factors considered to initiate treatment, expert opinion was graded the highest (mean grade ± SD = 3.2 ± 1.3), followed by fellowship training (3.2 ± 1.3). Conversely, previous studies (2.7 ± 1.2) and unspecified guidelines were considered least important (2.6 ± 1.6). Patient body mass index (2.0 ± 1.0) and postoperative mobilization (2.3 ± 1.0) were deemed most important and graded highly overall. Those who rated estimated blood loss with greater importance in anticoagulation initiation decision making were more likely to administer thromboprophylaxis at later times (hazard ratio [HR] = 0.68-0.71), while those who rated drain output with greater importance were likely to administer thromboprophylaxis at earlier times (HR = 1.32-1.43). CONCLUSION: Among our global cohort of spine surgeons, certain patient factors (ie, patient mobilization and body mass index) and practice-specific factors (ie, expert opinion and fellowship training) were considered to be most important when considering anticoagulation start times

    Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

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    Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation

    Unity in defence: honeybee workers exhibit conserved molecular responses to diverse pathogens

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    This is the final version of the article. Available from the publisher via the DOI in this record.Background: Organisms typically face infection by diverse pathogens, and hosts are thought to have developed specific responses to each type of pathogen they encounter. The advent of transcriptomics now makes it possible to test this hypothesis and compare host gene expression responses to multiple pathogens at a genome-wide scale. Here, we performed a meta-analysis of multiple published and new transcriptomes using a newly developed bioinformatics approach that filters genes based on their expression profile across datasets. Thereby, we identified common and unique molecular responses of a model host species, the honey bee (Apis mellifera), to its major pathogens and parasites: the Microsporidia Nosema apis and Nosema ceranae, RNA viruses, and the ectoparasitic mite Varroa destructor, which transmits viruses. Results: We identified a common suite of genes and conserved molecular pathways that respond to all investigated pathogens, a result that suggests a commonality in response mechanisms to diverse pathogens. We found that genes differentially expressed after infection exhibit a higher evolutionary rate than non-differentially expressed genes. Using our new bioinformatics approach, we unveiled additional pathogen-specific responses of honey bees; we found that apoptosis appeared to be an important response following microsporidian infection, while genes from the immune signalling pathways, Toll and Imd, were differentially expressed after Varroa/virus infection. Finally, we applied our bioinformatics approach and generated a gene co-expression network to identify highly connected (hub) genes that may represent important mediators and regulators of anti-pathogen responses. Conclusions: Our meta-analysis generated a comprehensive overview of the host metabolic and other biological processes that mediate interactions between insects and their pathogens. We identified key host genes and pathways that respond to phylogenetically diverse pathogens, representing an important source for future functional studies as well as offering new routes to identify or generate pathogen resilient honey bee stocks. The statistical and bioinformatics approaches that were developed for this study are broadly applicable to synthesize information across transcriptomic datasets. These approaches will likely have utility in addressing a variety of biological questions.This article is a joint effort of the working group TRANSBEE and an outcome of two workshops kindly supported by sDiv, the Synthesis Centre for Biodiversity Sciences within the German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, funded by the German Science Foundation (FZT 118). New datasets were performed thanks to the Insect Pollinators Initiative (IPI grant BB/I000100/1 and BB/I000151/1), with participation of the UK-USA exchange funded by the BBSRC BB/I025220/1 (datasets #4, 11 and 14). The IPI is funded jointly by the Biotechnology and Biological Sciences Research Council, the Department for Environment, Food and Rural Affairs, the Natural Environment Research Council, the Scottish Government and the Wellcome Trust, under the Living with Environmental Change Partnershi
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