Sample records for acute vascular events

  1. Early blood pressure lowering treatment in acute stroke. Ordinal analysis of vascular events in the Scandinavian Candesartan Acute Stroke Trial (SCAST).

    PubMed

    Jusufovic, Mirza; Sandset, Else Charlotte; Bath, Philip M; Berge, Eivind

    2016-08-01

    Early blood pressure-lowering treatment appears to be beneficial in patients with acute intracerebral haemorrhage and potentially in ischaemic stroke. We used a new method for analysis of vascular events in the Scandinavian Candesartan Acute Stroke Trial to see if the effect was dependent on the timing of treatment. Scandinavian Candesartan Acute Stroke Trial was a randomized controlled and placebo-controlled trial of candesartan within 30 h of ischaemic or haemorrhagic stroke. Of 2029 patients, 231 (11.4%) had a vascular event (vascular death, nonfatal stroke or nonfatal myocardial infarction) during the first 6 months. The modified Rankin Scale (mRS) score following a vascular event was used to categorize vascular events in order of severity: no event (n = 1798), minor (mRS 0-2, n = 59), moderately severe (mRS 3-4, n = 57) and major event (mRS 5-6, n = 115). We used ordinal logistic regression for analysis and adjusted for predefined prognostic variables. Candesartan had no overall effect on vascular events (adjusted common odds ratio 1.11, 95% confidence interval 0.84-1.47, P = 0.48), and the effects were the same in ischaemic and haemorrhagic stroke. Among the patients treated within 6 h, the adjusted common odds ratio for vascular events was 0.37, 95% confidence interval 0.16-0.84, P = 0.02, and there was no heterogeneity of effect between ischaemic and haemorrhagic strokes. Ordinal analysis of vascular events showed no overall effect of candesartan in the subacute phase of stroke. The effect of treatment given within 6 h of stroke onset appears promising, and will be addressed in ongoing trials. Ordinal analysis of vascular events is feasible and can be used in future trials.

  2. Does a birthday predispose to vascular events?

    PubMed

    Saposnik, Gustavo; Baibergenova, Akerke; Dang, Jason; Hachinski, Vladimir

    2006-07-25

    To examine the influence of birthdays on the onset and course of vascular events such as stroke, TIA, and acute myocardial infarction (AMI). This population-based study included all emergency department (ED) admissions due to ischemic stroke, TIA, or AMI from April 2002 to March 2004 in Ontario, Canada. All cases were identified through the National Ambulatory Care Reporting System. Calculations of daily and weekly numbers of events were centered on the patient's birthday and the week of the birthday. Statistical analyses include binomial tests and logistic regression. During the study period, there were 24,315 ED admissions with acute stroke, 16,088 with TIAs, and 29,090 with AMI. The observed number of vascular events during the birthday was higher than the expected daily number of visits for stroke (87 vs 67; p = 0.009), TIA (58 vs 44; p = 0.02), and AMI (97 vs 80; p = 0.027) but not for selected control conditions (asthma, appendicitis, head trauma). Vascular events were more likely to occur on birthday (242 vs 191; odds ratio [OR] = 1.27). No significant differences were observed during the birthday week for any of the conditions. Multivariate logistic regression showed that birthday vascular events were more likely to occur in patients with a history of hypertension (OR = 1.88; 95% CI 1.09 to 3.24). Sensitivity analyses with alternative definitions of birthday week did not alter the results. Stress associated with birthdays may trigger vascular events in patients with predisposing conditions.

  3. Acute neurovascular events in cancer patients receiving anti-vascular endothelial growth factor agents: Clinical experience in Paris University Hospitals.

    PubMed

    Tlemsani, Camille; Mir, Olivier; Psimaras, Dimitri; Vano, Yann-Alexandre; Ducreux, Michel; Escudier, Bernard; Rousseau, Benoit; Loirat, Delphine; Ceccaldi, Bernard; André, Thierry; Goldwasser, François; Ricard, Damien

    2016-10-01

    Despite the increasing and broadening use of agents targeting the vascular endothelial growth factor (VEGF) pathway, little is known on their acute neurovascular toxicities. This retrospective, multi-centre study examined the characteristics of patients with solid tumours who experienced an ischaemic or haemorrhagic stroke, a transient ischaemic accident (TIA) or a posterior reversible encephalopathy syndrome (PRES) while under anti-VEGF and until 8 weeks after termination of treatment and evaluated their management in our institutions from 2004 to 2014. Patients with newly diagnosed or progressive cerebral metastases at the time of the acute neurovascular event were excluded. Thirty-four patients (55.9% men) were identified, and experienced either ischaemic stroke (n = 18), PRES (n = 9), TIA (n = 6) or haemorrhagic stroke (n = 1). At initiation of anti-VEGF agents, 64.7% of patients had previous cardiovascular risk factors, and 52.9% had hypertension. Eight patients (23.5%) had received cerebral radiotherapy, five of which concomitantly to anti-VEGF treatment. Six (17%) patients died in the 8 weeks following the acute neurovascular event, and only 55.9% recovered their initial neurological status. Overall, 1-year and 2-year survival rates after the acute neurovascular event were 67.9% and 50%, respectively. When anti-VEGF agents were reintroduced (n = 6), severe vascular toxicity recurred in two patients. Neurovascular events under VEGF treatments are potentially severe, and the management of comorbid conditions has to be improved. A prospective collection of data and standardised management of such events is therefore being structured in our institutions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Retinal microvascular changes and subsequent vascular events after ischemic stroke.

    PubMed

    De Silva, D A; Manzano, J J F; Liu, E Y; Woon, F-P; Wong, W-X; Chang, H-M; Chen, C; Lindley, R I; Wang, J J; Mitchell, P; Wong, T-Y; Wong, M-C

    2011-08-30

    Retinal microvasculature changes are associated with vascular events including stroke in healthy populations. It is not known whether retinal microvascular changes predict recurrent vascular events after ischemic stroke. We examined the relationship between retinal microvascular signs and subsequent vascular events in a prospective cohort of 652 acute ischemic stroke patients admitted to a tertiary hospital in Singapore from 2005 to 2007. Retinal photographs taken within 1 week of stroke onset were assessed in a masked manner for quantitative and qualitative measures. Follow-up data over 2-4 years were obtained by standardized telephone interview and then were verified from medical records. Predictors of recurrent vascular events (cerebrovascular, coronary, vascular death, and composite vascular events) were determined using Cox regression models. Follow-up data over a median of 29 months were obtained for 89% (652 patients) of the cohort. After adjustment for covariates including traditional risk factors and index stroke etiology, patients with severe arteriovenous nicking (AVN) were more likely to have a recurrent cerebrovascular event (hazard ratio [HR] 2.28, 95% confidence interval [CI] 1.20-4.33) compared with those without AVN. Patients with severe focal arteriolar narrowing (FAN) were more likely to have a recurrent cerebrovascular event (HR 2.75, 95% CI 1.14-6.63) or subsequent composite vascular event (HR 2.77, 95% CI 1.31-5.86) compared to those without FAN. Retinal microvascular changes predicted subsequent vascular events after ischemic stroke, independent of traditional risk factors and stroke subtype. Thus, retinal imaging has a potential role in predicting the risk of recurrent vascular events after ischemic stroke and in understanding novel vascular risk factors.

  5. Access to primary health care for acute vascular events in rural low income settings: a mixed methods study.

    PubMed

    Ahmed, Shyfuddin; Chowdhury, Muhammad Ashique Haider; Khan, Md Alfazal; Huq, Nafisa Lira; Naheed, Aliya

    2017-01-18

    Cardiovascular diseases (CVDs) are the leading cause of global mortality. Among the CVDs, acute vascular events (AVE) mainly ischemic heart diseases and stroke are the largest contributors. To achieve 25% reduction in preventable deaths from CVDs by 2025, health systems need to be equipped with extended service coverage in order to provide person-centered care. The overall goal of this proposed study is to assess access to health care in-terms of service availability, care seeking patterns and barriers to access care after AVE in rural Bangladesh. We will consider myocardial infarction (MI) and stroke as acute vascular events. We will conduct a mixed methods study in rural Matlab, Bangladesh. This study will comprise of a) health facility survey, b) structured questionnaire interview and c) qualitative study. We will assess service availabilities by creating an inventory of public and private health facilities. Readiness of the facilities to deliver services for AVE will be assessed through a health facility survey using 'service availability and readiness assessment' (SARA) tools of the World Health Organization (WHO). We will interview survivors of AVE and caregivers (present and accompanied the person during the event) of person who died from AVE for exploring patterns of care seeking during an AVE. For exploring barriers to access care for AVE, we will conduct in-depth interview with survivors of AVE and caregivers of the person who died from AVE. We will also conduct key informant interviews with the service providers at primary health care (PHC) facilities and government high level officials at central health administration of Bangladesh. This study will provide a comprehensive picture of access to primary health care services during acute cardiovascular events as stroke & MI in rural context of Bangladesh. It will explore available service facilities in rural area for management, utilization of services and barriers to access care during an acute emergency

  6. Predictive Value of Pulse Pressure in Acute Ischemic Stroke for Future Major Vascular Events.

    PubMed

    Lee, Keon-Joo; Kim, Beom Joon; Han, Moon-Ku; Kim, Joon-Tae; Cho, Ki-Hyun; Shin, Dong-Ick; Yeo, Min-Ju; Cha, Jae-Kwan; Kim, Dae-Hyun; Nah, Hyun-Wook; Kim, Dong-Eog; Ryu, Wi-Sun; Park, Jong-Moo; Kang, Kyusik; Lee, Soo Joo; Oh, Mi-Sun; Yu, Kyung-Ho; Lee, Byung-Chul; Hong, Keun-Sik; Cho, Yong-Jin; Choi, Jay Chol; Sohn, Sung Il; Hong, Jeong-Ho; Park, Tai Hwan; Park, Sang-Soon; Kwon, Jee-Hyun; Kim, Wook-Joo; Lee, Jun; Lee, Ji Sung; Lee, Juneyoung; Gorelick, Philip B; Bae, Hee-Joon

    2018-01-01

    This study aimed to investigate whether pulse pressure (PP) obtained during the acute stage of ischemic stroke can be used as a predictor for future major vascular events. Using a multicenter prospective stroke registry database, patients who were hospitalized for ischemic stroke within 48 hours of onset were enrolled in this study. We analyzed blood pressure (BP) data measured during the first 3 days from onset. Primary and secondary outcomes were time to a composite of stroke recurrence, myocardial infarction, all-cause death, and time to stroke recurrence, respectively. Of 9840 patients, 4.3% experienced stroke recurrence, 0.2% myocardial infarction, and 7.3% death during a 1-year follow-up period. In Cox proportional hazards models including both linear and quadratic terms of PP, PP had a nonlinear J-shaped relationship with primary (for a quadratic term of PP, P =0.004) and secondary ( P <0.001) outcomes. The overall effects of PP and other BP parameters on primary and secondary outcomes were also significant ( P <0.05). When predictive power of BP parameters was compared using a statistic of -2 log-likelihood differences, PP was a stronger predictor than systolic BP (8.49 versus 5.91; 6.32 versus 4.56), diastolic BP (11.42 versus 11.05; 10.07 versus 4.56), and mean atrial pressure (8.75 versus 5.91; 7.03 versus 4.56) for the primary and secondary outcomes, respectively. Our study shows that PP when measured in the acute period of ischemic stroke has nonlinear J-shaped relationships with major vascular events and stroke recurrence, and may have a stronger predictive power than other commonly used BP parameters. © 2017 American Heart Association, Inc.

  7. Lipoprotein(a) levels predict adverse vascular events after acute myocardial infarction.

    PubMed

    Mitsuda, Takayuki; Uemura, Yusuke; Ishii, Hideki; Takemoto, Kenji; Uchikawa, Tomohiro; Koyasu, Masayoshi; Ishikawa, Shinji; Miura, Ayako; Imai, Ryo; Iwamiya, Satoshi; Ozaki, Yuta; Kato, Tomohiro; Shibata, Rei; Watarai, Masato; Murohara, Toyoaki

    2016-12-01

    Lipoprotein(a) [Lp(a)], which is genetically determined, has been reported as an independent risk factor for atherosclerotic vascular disease. However, the prognostic value of Lp(a) for secondary vascular events in patients after coronary artery disease has not been fully elucidated. This 3-year observational study included a total of 176 patients with ST-elevated myocardial infarction (STEMI), whose Lp(a) levels were measured within 24 h after primary percutaneous coronary intervention. We divided enrolled patients into two groups according to Lp(a) level and investigated the association between Lp(a) and the incidence of major adverse cardiac and cerebrovascular events (MACCE). A Kaplan-Meier analysis demonstrated that patients with higher Lp(a) levels had a higher incidence of MACCE than those with lower Lp(a) levels (log-rank P = 0.034). A multivariate Cox regression analysis revealed that Lp(a) levels were independently correlated with the occurrence of MACCE after adjusting for other classical risk factors of atherosclerotic vascular diseases (hazard ratio 1.030, 95 % confidence interval: 1.011-1.048, P = 0.002). In receiver-operating curve analysis, the cutoff value to maximize the predictive power of Lp(a) was 19.0 mg/dl (area under the curve = 0.674, sensitivity 69.2 %, specificity 62.0 %). Evaluation of Lp(a) in addition to the established coronary risk factors improved their predictive value for the occurrence of MACCE. In conclusion, Lp(a) levels at admission independently predict secondary vascular events in patients with STEMI. Lp(a) might provide useful information for the development of secondary prevention strategies in patients with myocardial infarction.

  8. Lipoprotein(a) Levels and Recurrent Vascular Events After First Ischemic Stroke.

    PubMed

    Lange, Kristin S; Nave, Alexander H; Liman, Thomas G; Grittner, Ulrike; Endres, Matthias; Ebinger, Martin

    2017-01-01

    The association of elevated lipoprotein(a) (Lp(a)) levels and the incidence of cardiovascular disease, especially coronary heart disease and ischemic stroke, is well established. However, evidence on the association between Lp(a) levels and residual vascular risk in stroke survivors is lacking. We aimed to elucidate the risk for recurrent cardiovascular and cerebrovascular events in the patients with first-ever ischemic stroke with elevated Lp(a). All patients with acute ischemic stroke who participated in the prospective Berlin C&S study (Cream & Sugar) between January 2009 and August 2014 with available 12-month follow-up data and stored blood samples were eligible for inclusion. Lp(a) levels were determined in serum samples using an isoform-insensitive nephelometry assay. We assessed the risk for the composite vascular end point of ischemic stroke, transient ischemic attack, myocardial infarction, nonelective coronary revascularization, and cardiovascular death with elevated Lp(a) defined as >30 mg/dL using Cox regression analyses. Of 465 C&S study participants, 250 patients were included into this substudy with a median National Institutes of Health Stroke Scale score of 2 (1-4). Twenty-six patients (10%) experienced a recurrent vascular event during follow-up. Among patients with normal Lp(a) levels, 11 of 157 subjects (7%) experienced an event at a median time of 161 days (interquartile range, 19-196 days), whereas in patients with elevated Lp(a) levels, 15 of 93 subjects (16%) experienced an event at a median time of 48 days (interquartile range, 9-194 days; P=0.026). The risk for a recurrent event was significantly higher in patients with elevated Lp(a) levels after adjustment for potential confounders (hazard ratio, 2.60; 95% confidence interval, 1.19-5.67; P=0.016). Elevated Lp(a) levels are associated with a higher risk for combined vascular event recurrence in patients with acute, first-ever ischemic stroke. This finding should be validated in larger

  9. [Acute hepatic vascular complications].

    PubMed

    Ochs, A

    2011-07-01

    Acute hepatic vascular complications are rare. Acute portal vein thrombosis (PVT) and the Budd-Chiari syndrome (BSC) are the leading causes. Coagulopathy and local factors are present in up to 80% of cases. Diagnosis is established by colour-coded Doppler sonography, contrast-enhanced computed tomography or magnetic resonance imaging. Patients with acute PVT present with abdominal pain and disturbed intestinal motility. In the absence of cirrhosis anticoagulation with heparin is established followed by oral anticoagulation. In severe cases, surgical thrombectomy or transjugular thrombolysis with stent shunt may be necessary. Acute or fulminant BCS may require emergency liver transplantation or a transjugular intrahepatic portosystemic stent shunt, if patients present with acute liver failure. Milder cases receive anticoagulation for thrombolysis of occluded hepatic veins. Sinusoidal obstruction syndrome (SOS) is diagnosed after total body irradiation or chemotherapy, the term SOS replacing the former veno-occlusive disease. The treatment of congenital vascular malformations, complications in the setting of OLTX as well as patients with hepatic involvement of hereditary hemorrhagic telangiectasia requires significant expertise in a multidisciplinary approach.

  10. Acute rejection in vascularized composite allotransplantation.

    PubMed

    Fischer, Sebastian; Lian, Christine G; Kueckelhaus, Maximilian; Strom, Terry B; Edelman, Elazer R; Clark, Rachel A; Murphy, George F; Chandraker, Anil K; Riella, Leonardo V; Tullius, Stefan G; Pomahac, Bohdan

    2014-12-01

    Acute rejection is the most common complication after vascularized composite allotransplantation (VCA). This review provides a state-of-the-art analysis of prevention, diagnosis and treatment of acute rejection episodes and highlights recent findings with the potential to improve patient care and enhance understanding of the underlying biologic processes. Recent reports suggest that maintenance immunosuppression dose reduction and steroid withdrawal are realistic goals in VCA, despite the known high immunogenicity of the skin component. It appears that utilization of sentinel flaps, in-depth histological analyses and application of novel biomarkers have facilitated early diagnosis and characterization of acute rejection episodes, leading to timely institution of appropriate therapy. The successful management of the first highly sensitized face transplant recipient suggests the possibility of carefully considering these high-risk VCA candidates for transplantation. Acute rejection is higher in VCA than in any other organ in the field of transplantation, although most episodes are controlled by high-dose steroids and optimization of maintenance immunosuppression. Because of limitations in patient number and the duration of follow-up, the long-term safety and effectiveness of VCA remain unclear. Moreover, the tests currently used to diagnose acute rejection are of limited value. Better diagnostic tools and a better understanding of the immunologic events during acute rejection are therefore needed to improve diagnosis, treatment and outcomes of this life-changing restorative surgery.

  11. Diffuse corpus callosum infarction - Rare vascular entity with differing etiology.

    PubMed

    Mahale, Rohan; Mehta, Anish; Buddaraju, Kiran; John, Aju Abraham; Javali, Mahendra; Srinivasa, Rangasetty

    2016-01-15

    Infarctions of the corpus callosum are rare vascular events. It is relatively immune to vascular insult because of its rich vascular supply from anterior and posterior circulations of brain. Report of 3 patients with largely diffuse acute corpus callosum infarction. 3 patients with largely diffuse acute corpus callosum infarction were studied and each of these 3 patients had 3 different aetiologies. The 3 different aetiologies of largely diffuse acute corpus callosum infarction were cardioembolism, tuberculous arteritis and takayasu arteritis. Diffuse corpus callosum infarcts are rare events. This case series narrates the three different aetiologies of diffuse acute corpus callosum infarction which is a rare vascular event. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Red Wine Prevents the Acute Negative Vascular Effects of Smoking.

    PubMed

    Schwarz, Viktoria; Bachelier, Katrin; Schirmer, Stephan H; Werner, Christian; Laufs, Ulrich; Böhm, Michael

    2017-01-01

    Moderate consumption of red wine is associated with fewer cardiovascular events. We investigated whether red wine consumption counteracts the adverse vascular effects of cigarette smoking. Participants smoked 3 cigarettes alone or after drinking a titrated volume of red wine. Clinical chemistry, blood counts, plasma cytokine enzyme-linked immunosorbent assays, immunomagnetic separation of CD14 + monocytes for gene expression analysis, fluorescence-activated cell sorting for microparticles, and isolation of circulating mononuclear cells to measure telomerase activity were performed, and urine cotinine levels were quantified. Compared with baseline, leukocytosis (P = .019), neutrophilia (P <.001), lymphopenia (P <.001), and eosinopenia (P = .008) were observed after only smoking. Endothelial and platelet-, monocyte-, and leukocyte-derived microparticles (P <.001 each) were elevated. In monocytes, messenger RNA expression of interleukin (IL)-6 (2.6- ± 0.57-fold), tumor necrosis factor alpha (2.2- ± 0.62-fold), and IL-1b (2.3- ± 0.44-fold) were upregulated, as was IL-6 (1.2 ± 0.12-fold) protein concentration in plasma. Smoking acutely inhibited mononuclear cell telomerase activity. Markers of endothelial damage, inflammation, and cellular aging were completely attenuated by red wine consumption. Cigarette smoke results in acute endothelial damage, vascular and systemic inflammation, and indicators of the cellular aging processes in otherwise healthy nonsmokers. Pretreatment with red wine was preventive. The findings underscore the magnitude of acute damage exerted by cigarette smoking in "occasional lifestyle smokers" and demonstrate the potential of red wine as a protective strategy to avert markers of vascular injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Brain Arterial Diameters as a Risk Factor for Vascular Events.

    PubMed

    Gutierrez, Jose; Cheung, Ken; Bagci, Ahmet; Rundek, Tatjana; Alperin, Noam; Sacco, Ralph L; Wright, Clinton B; Elkind, Mitchell S V

    2015-08-06

    Arterial luminal diameters are routinely used to assess for vascular disease. Although small diameters are typically considered pathological, arterial dilatation has also been associated with disease. We hypothesize that extreme arterial diameters are biomarkers of the risk of vascular events. Participants in the Northern Manhattan Study who had a time-of-flight magnetic resonance angiography were included in this analysis (N=1034). A global arterial Z-score, called the brain arterial remodeling (BAR) score, was obtained by averaging the measured diameters within each individual. Individuals with a BAR score <-2 SDs were considered to have the smallest diameters, individuals with a BAR score >-2 and <2 SDs had average diameters, and individuals with a BAR score >2 SDs had the largest diameters. All vascular events were recorded prospectively after the brain magnetic resonance imaging. Spline curves and incidence rates were used to test our hypothesis. The association of the BAR score with death (P=0.001), vascular death (P=0.02), any vascular event (P=0.05), and myocardial infarction (P=0.10) was U-shaped except for ischemic stroke (P=0.74). Consequently, incidence rates for death, vascular death, myocardial infarction, and any vascular event were higher in individuals with the largest diameters, whereas individuals with the smallest diameters had a higher incidence of death, vascular death, any vascular event, and ischemic stroke compared with individuals with average diameters. The risk of death, vascular death, and any vascular event increased at both extremes of brain arterial diameters. The pathophysiology linking brain arterial remodeling to systemic vascular events needs further research. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  14. Retinal vascular changes are a marker for cerebral vascular diseases

    PubMed Central

    Moss, Heather E.

    2016-01-01

    The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk. PMID:26008809

  15. The Bangladesh Risk of Acute Vascular Events (BRAVE) Study: objectives and design.

    PubMed

    Chowdhury, Rajiv; Alam, Dewan S; Fakir, Ismail Ibrahim; Adnan, Sheikh Daud; Naheed, Aliya; Tasmin, Ishrat; Monower, Md Mostafa; Hossain, Farzana; Hossain, Fatema Mahjabin; Rahman, Md Mostafizur; Afrin, Sadia; Roy, Anjan Kumar; Akter, Minara; Sume, Sima Akter; Biswas, Ajoy Kumer; Pennells, Lisa; Surendran, Praveen; Young, Robin D; Spackman, Sarah A; Hasan, Khaled; Harshfield, Eric; Sheikh, Nasir; Houghton, Richard; Saleheen, Danish; Howson, Joanna M M; Butterworth, Adam S; Raqib, Rubhana; Majumder, Abdulla Al Shafi; Danesh, John; Di Angelantonio, Emanuele

    2015-07-01

    During recent decades, Bangladesh has experienced a rapid epidemiological transition from communicable to non-communicable diseases. Coronary heart disease (CHD), with myocardial infarction (MI) as its main manifestation, is a major cause of death in the country. However, there is limited reliable evidence about its determinants in this population. The Bangladesh Risk of Acute Vascular Events (BRAVE) study is an epidemiological bioresource established to examine environmental, genetic, lifestyle and biochemical determinants of CHD among the Bangladeshi population. By early 2015, the ongoing BRAVE study had recruited over 5000 confirmed first-ever MI cases, and over 5000 controls "frequency-matched" by age and sex. For each participant, information has been recorded on demographic factors, lifestyle, socioeconomic, clinical, and anthropometric characteristics. A 12-lead electrocardiogram has been recorded. Biological samples have been collected and stored, including extracted DNA, plasma, serum and whole blood. Additionally, for the 3000 cases and 3000 controls initially recruited, genotyping has been done using the CardioMetabochip+ and the Exome+ arrays. The mean age (standard deviation) of MI cases is 53 (10) years, with 88 % of cases being male and 46 % aged 50 years or younger. The median interval between reported onset of symptoms and hospital admission is 5 h. Initial analyses indicate that Bangladeshis are genetically distinct from major non-South Asian ethnicities, as well as distinct from other South Asian ethnicities. The BRAVE study is well-placed to serve as a powerful resource to investigate current and future hypotheses relating to environmental, biochemical and genetic causes of CHD in an important but under-studied South Asian population.

  16. Betaine and Secondary Events in an Acute Coronary Syndrome Cohort

    PubMed Central

    Lever, Michael; George, Peter M.; Elmslie, Jane L.; Atkinson, Wendy; Slow, Sandy; Molyneux, Sarah L.; Troughton, Richard W.; Richards, A. Mark; Frampton, Christopher M.; Chambers, Stephen T.

    2012-01-01

    Background Betaine insufficiency is associated with unfavourable vascular risk profiles in metabolic syndrome patients. We investigated associations between betaine insufficiency and secondary events in acute coronary syndrome patients. Methods Plasma (531) and urine (415) samples were collected four months after discharge following an acute coronary event. Death (34), secondary acute myocardial infarction (MI) (70) and hospital admission for heart failure (45) events were recorded over a median follow-up of 832 days. Principal Findings The highest and lowest quintiles of urinary betaine excretion associated with risk of heart failure (p = 0.0046, p = 0.013 compared with middle 60%) but not with subsequent acute MI. The lowest quintile of plasma betaine was associated with subsequent acute MI (p = 0.014), and the top quintile plasma betaine with heart failure (p = 0.043), especially in patients with diabetes (p<0.001). Top quintile plasma concentrations of dimethylglycine (betaine metabolite) and top quintile plasma homocysteine both associated with all three outcomes, acute MI (p = 0.004, <0.001), heart failure (p = 0.027, p<0.001) and survival (p<0.001, p<0.001). High homocysteine was associated with high or low betaine excretion in >60% of these subjects (p = 0.017). Median NT-proBNP concentrations were lowest in the middle quintile of plasma betaine concentration (p = 0.002). Conclusions Betaine insufficiency indicates increased risk of secondary heart failure and acute MI. Its association with elevated homocysteine may partly explain the disappointing results of folate supplementation. In some patients, especially with diabetes, elevated plasma betaine also indicates increased risk. PMID:22649561

  17. Association of Lp-PLA2-A and early recurrence of vascular events after TIA and minor stroke.

    PubMed

    Lin, Jinxi; Zheng, Hongwei; Cucchiara, Brett L; Li, Jiejie; Zhao, Xingquan; Liang, Xianhong; Wang, Chunxue; Li, Hao; Mullen, Michael T; Johnston, S Claiborne; Wang, Yilong; Wang, Yongjun

    2015-11-03

    To determine the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) measured in the acute period and the short-term risk of recurrent vascular events in patients with TIA or minor stroke. We measured Lp-PLA2 activity (Lp-PLA2-A) in a subset of 3,201 participants enrolled in the CHANCE (Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events) trial. Participants with TIA or minor stroke were enrolled within 24 hours of symptom onset and randomized to single or dual antiplatelet therapy. In the current analysis, the primary outcome was defined as the composite of ischemic stroke, myocardial infarction, or death within 90 days. The composite endpoint occurred in 299 of 3,021 participants (9.9%). The population average Lp-PLA2-A level was 209 ± 59 nmol/min/mL (95% confidence interval [CI] 207-211). Older age, male sex, and current smoking were associated with higher Lp-PLA2-A levels. Lp-PLA2-A was significantly associated with the primary endpoint (adjusted hazard ratio 1.07, 95% CI 1.01-1.13 for every 30 nmol/min/mL increase). Similar results were seen for ischemic stroke alone. Adjustment for low-density lipoprotein cholesterol attenuated the association between Lp-PLA2-A and the primary endpoint (adjusted hazard ratio 1.04, 95% CI 0.97-1.11 for every 30 nmol/min/mL increase). Higher levels of Lp-PLA2-A in the acute period are associated with increased short-term risk of recurrent vascular events. © 2015 American Academy of Neurology.

  18. Dental procedures and risk of experiencing a second vascular event in a Medicare population.

    PubMed

    Skaar, Daniel; O'Connor, Heidi; Lunos, Scott; Luepker, Russell; Michalowicz, Bryan S

    2012-11-01

    Practice guidelines historically have recommended postponing dental care after ischemic vascular events. The authors examined an administrative data set to determine whether dental procedures increased patients' risk of experiencing a second vascular event. The authors examined a data set of 50,329 participants in the Medicare Current Beneficiary Survey to identify those who had had a vascular event (n = 2,035) and a second event (n = 445) while in the survey. They used Cox proportional hazards regression to study associations between dental procedures performed within 30, 60, 90 or 180 days after a first event and the risk of experiencing a second vascular event. Dental procedures of any kind, and invasive procedures considered separately, were not associated with patients' risk of experiencing second vascular events across all periods examined. Most hazard ratios associated with dental procedures were less than 1.0, although none differed significantly from 1.0. The authors found that community-dwelling Medicare beneficiaries who underwent dental procedures within 30 to 180 days after an ischemic vascular event, including those that produce a bacteremia consistently, were not at an increased risk of experiencing a second event. The results of this study suggest that clinicians should reassess historical recommendations that dental care in this population be postponed for as long as six months after an ischemic vascular event.

  19. Shift work and vascular events: systematic review and meta-analysis.

    PubMed

    Vyas, Manav V; Garg, Amit X; Iansavichus, Arthur V; Costella, John; Donner, Allan; Laugsand, Lars E; Janszky, Imre; Mrkobrada, Marko; Parraga, Grace; Hackam, Daniel G

    2012-07-26

    To synthesise the association of shift work with major vascular events as reported in the literature. Systematic searches of major bibliographic databases, contact with experts in the field, and review of reference lists of primary articles, review papers, and guidelines. Observational studies that reported risk ratios for vascular morbidity, vascular mortality, or all cause mortality in relation to shift work were included; control groups could be non-shift ("day") workers or the general population. Study quality was assessed with the Downs and Black scale for observational studies. The three primary outcomes were myocardial infarction, ischaemic stroke, and any coronary event. Heterogeneity was measured with the I(2) statistic and computed random effects models. 34 studies in 2,011,935 people were identified. Shift work was associated with myocardial infarction (risk ratio 1.23, 95% confidence interval 1.15 to 1.31; I(2)=0) and ischaemic stroke (1.05, 1.01 to 1.09; I(2)=0). Coronary events were also increased (risk ratio 1.24, 1.10 to 1.39), albeit with significant heterogeneity across studies (I(2)=85%). Pooled risk ratios were significant for both unadjusted analyses and analyses adjusted for risk factors. All shift work schedules with the exception of evening shifts were associated with a statistically higher risk of coronary events. Shift work was not associated with increased rates of mortality (whether vascular cause specific or overall). Presence or absence of adjustment for smoking and socioeconomic status was not a source of heterogeneity in the primary studies. 6598 myocardial infarctions, 17,359 coronary events, and 1854 ischaemic strokes occurred. On the basis of the Canadian prevalence of shift work of 32.8%, the population attributable risks related to shift work were 7.0% for myocardial infarction, 7.3% for all coronary events, and 1.6% for ischaemic stroke. Shift work is associated with vascular events, which may have implications for public

  20. Acute effect of mineralocorticoid receptor antagonism on vascular function in healthy older adults.

    PubMed

    Hwang, Moon-Hyon; Yoo, Jeung-Ki; Luttrell, Meredith; Kim, Han-Kyul; Meade, Thomas H; English, Mark; Talcott, Susanne; Jaffe, Iris Z; Christou, Demetra D

    2016-01-01

    Mineralocorticoid receptor (MR) activation by aldosterone may regulate vascular function in health or contribute to vascular dysfunction in cardiovascular disease. Whether the effects are beneficial or detrimental to vascular function appear to be dependent on the integrity of the vascular endothelium and whether the responses are short-term or chronic. Acute modulation of MR activation has resulted in conflicting outcomes on vascular function in young healthy adults. Little is known about the vascular role of aldosterone and MR activation in healthy human aging. The primary objective of this study was to examine whether acute inhibition of MR by the selective antagonist eplerenone, influences vascular function in healthy older adults. We performed a randomized, double-blind, placebo-controlled crossover study in 22 adults (61±1 years; mean±SE, 53-79 years) who were free from overt clinical cardiovascular disease. We measured brachial artery flow-mediated endothelium-dependent dilation and endothelium-independent dilation to sublingual nitroglycerin (0.4 mg) following eplerenone (100 mg/dose, 2 doses, 24h between doses) or placebo. In response to acute MR antagonism, flow-mediated dilation decreased by 19% (from 6.9±0.5 to 5.6±0.6%, P=0.02; placebo vs. eplerenone). Endothelial nitric oxide synthase (eNOS) activity also decreased following MR antagonism based on the ratio of phosphorylated eNOS(Ser1177) to total eNOS (1.53±0.08 vs. 1.29±0.06, P=0.02). Nitroglycerin-induced dilation and blood pressure were unaffected (nitroglycerin-induced dilation: 21.9±1.9 vs. 21.0±1.5%, P=0.5 and systolic/diastolic blood pressure: 135/77±4/2 vs. 134/77±4/2 mmHg, P≥0.6). In conclusion, acute MR antagonism impairs vascular endothelial function in healthy older adults without influencing vascular smooth muscle responsiveness to exogenous nitric oxide or blood pressure. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Platelet Activating Factor Contributes to Vascular Leak in Acute Dengue Infection

    PubMed Central

    Jeewandara, Chandima; Gomes, Laksiri; Wickramasinghe, N.; Gutowska-Owsiak, Danuta; Waithe, Dominic; Paranavitane, S. A.; Shyamali, N. L. A.; Ogg, Graham S.; Malavige, Gathsaurie Neelika

    2015-01-01

    Background Although plasma leakage is the hallmark of severe dengue infections, the factors that cause increased vascular permeability have not been identified. As platelet activating factor (PAF) is associated with an increase in vascular permeability in other diseases, we set out to investigate its role in acute dengue infection. Materials and Methods PAF levels were initially assessed in 25 patients with acute dengue infection to determine if they were increased in acute dengue. For investigation of the kinetics of PAF, serial PAF values were assessed in 36 patients. The effect of dengue serum on tight junction protein ZO-1 was determined by using human endothelial cell lines (HUVECs). The effect of dengue serum on and trans-endothelial resistance (TEER) was also measured on HUVECs. Results PAF levels were significantly higher in patients with acute dengue (n = 25; p = 0.001) when compared to healthy individuals (n = 12). In further investigation of the kinetics of PAF in serial blood samples of patients (n = 36), PAF levels rose just before the onset of the critical phase. PAF levels were significantly higher in patients with evidence of vascular leak throughout the course of the illness when compared to those with milder disease. Serum from patients with dengue significantly down-regulated expression of tight junction protein, ZO-1 (p = 0.004), HUVECs. This was significantly inhibited (p = 0.004) by use of a PAF receptor (PAFR) blocker. Serum from dengue patients also significantly reduced TEER and this reduction was also significantly (p = 0.02) inhibited by prior incubation with the PAFR blocker. Conclusion Our results suggest the PAF is likely to be playing a significant role in inducing vascular leak in acute dengue infection which offers a potential target for therapeutic intervention. PMID:25646838

  2. Inter-arm systolic blood pressure differences, relations with future vascular events and mortality in patients with and without manifest vascular disease.

    PubMed

    Kranenburg, Guido; Spiering, Wilko; de Jong, Pim A; Kappelle, L Jaap; de Borst, Gert Jan; Cramer, Maarten J; Visseren, Frank L J; Aboyans, Victor; Westerink, Jan

    2017-10-01

    Inter-arm systolic blood pressure difference (SBPD) is an easily obtained patient characteristic which relates to vascular disease. We aimed to identify determinants of large inter-arm SBPD and to investigate the relation between inter-arm SBPD and vascular events in patients with and without manifest vascular disease. In a cohort of 7344 patients with manifest vascular disease or vascular risk factors alone enrolled in the Second Manifestations of ARTerial disease (SMART) study, single bilateral non-simultaneous blood pressure measurements were performed. Logistic and Cox regression was used to identify determinants of large inter-arm SBPD (≥15mmHg) and to investigate the relation between inter-arm SBPD and vascular events (composite of non-fatal myocardial infarction, stroke, and vascular mortality) and all-cause mortality. In all patients the median inter-arm SBPD was 7mmHg (IQR 3-11) and 1182 (16%) patients had inter-arm SBPD ≥15mmHg. Higher age, higher systolic blood pressure, diabetes mellitus, peripheral artery disease, carotid artery stenosis, higher carotid intima-media thickness, and lower ankle-brachial indices were related to large inter-arm SBPD (≥15mmHg). Each 5mmHg increase in inter-arm SBPD was related to a 12% higher risk of vascular events in patients without manifest vascular disease (HR 1.12; 95% CI 1.00-1.27), whereas no relation was apparent in patients with manifest vascular disease (HR 0.98; 95% CI 0.93-1.04, interaction p-value 0.036). Inter-arm SBPD was not related to all-cause mortality (HR 1.05; 95% CI 0.93-1.19). Inter-arm SBPD relates to a higher risk of vascular events in patients without manifest vascular disease, whereas this relation is not apparent in patients with manifest vascular disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. A vascular laboratory protocol for improving and managing after-hours suspected acute deep venous thrombosis.

    PubMed

    Martin, Angela H; Eckert, George; Lemmon, Gary W; Sawchuk, Alan; Dalsing, Michael C

    2014-04-01

    This study reviews the clinical and workforce impact of a suggested protocol designed for the management of suspected acute deep venous thrombosis (DVT) in patients seen after standard vascular laboratory business hours. The protocol included the use of Wells score, D-dimer and a single dose of therapeutic anticoagulant to defer venous duplex ultrasound (VDU) testing until routine business hours unless contraindicated. Information was collected on medical history, physical exam and the timing of any diagnostic studies and treatment provided. Over 15% of studies done after-hours were deemed unnecessary by our protocol and in every individual the results were negative for an acute DVT. There were no adverse events from a one-time dose of anticoagulant. Limiting emergency VDU coverage to evaluate for acute DVT based on a management protocol can eliminate unnecessary after-hours VDU testing without having a negative impact on patient care.

  4. Moderate Champagne consumption promotes an acute improvement in acute endothelial-independent vascular function in healthy human volunteers.

    PubMed

    Vauzour, David; Houseman, Emily J; George, Trevor W; Corona, Giulia; Garnotel, Roselyne; Jackson, Kim G; Sellier, Christelle; Gillery, Philippe; Kennedy, Orla B; Lovegrove, Julie A; Spencer, Jeremy P E

    2010-04-01

    Epidemiological studies have suggested an inverse correlation between red wine consumption and the incidence of CVD. However, Champagne wine has not been fully investigated for its cardioprotective potential. In order to assess whether acute and moderate Champagne wine consumption is capable of modulating vascular function, we performed a randomised, placebo-controlled, cross-over intervention trial. We show that consumption of Champagne wine, but not a control matched for alcohol, carbohydrate and fruit-derived acid content, induced an acute change in endothelium-independent vasodilatation at 4 and 8 h post-consumption. Although both Champagne wine and the control also induced an increase in endothelium-dependent vascular reactivity at 4 h, there was no significant difference between the vascular effects induced by Champagne or the control at any time point. These effects were accompanied by an acute decrease in the concentration of matrix metalloproteinase (MMP-9), a significant decrease in plasma levels of oxidising species and an increase in urinary excretion of a number of phenolic metabolites. In particular, the mean total excretion of hippuric acid, protocatechuic acid and isoferulic acid were all significantly greater following the Champagne wine intervention compared with the control intervention. Our data suggest that a daily moderate consumption of Champagne wine may improve vascular performance via the delivery of phenolic constituents capable of improving NO bioavailability and reducing matrix metalloproteinase activity.

  5. Adverse events with intravitreal injection of vascular endothelial growth factor inhibitors: nested case-control study

    PubMed Central

    Gill, Sudeep S; Bronskill, Susan E; Paterson, J Michael; Whitehead, Marlo

    2012-01-01

    Objective To assess the risk of systemic adverse events associated with intravitreal injections of vascular endothelial growth factor inhibiting drugs. Design Population based nested case-control study. Setting Ontario, Canada. Participants 91 378 older adults with a history of physician diagnosed retinal disease identified between 1 April 2006 and 31 March 2011. Cases were 1477 patients admitted to hospital for ischaemic stroke, 2229 admitted for an acute myocardial infarction, 1059 admitted or assessed in an emergency department for venous thromboembolism, and 2623 admitted for congestive heart failure. Event-free controls (at a ratio of 5:1) were matched to cases on the basis of year of birth, sex, history of the outcome in the previous 5 years, and diabetes. Main exposure measure Exposure to vascular endothelial growth factor inhibiting drugs identified within 180 days before the index date. Results After adjustment for potential confounders, participants who had ischaemic stroke, acute myocardial infarction, congestive heart failure, or venous thromboembolism were not more likely than control participants to have been exposed to either bevacizumab (adjusted odds ratios of 0.95 (95% confidence interval 0.68 to 1.34) for ischaemic stroke, 1.04 (0.77 to 1.39) for acute myocardial infarction, 0.81 (0.49 to 1.34) for venous thromboembolism, and 1.21 (0.91 to 1.62) for congestive heart failure) or ranibizumab (adjusted odds ratios 0.87 (0.68 to 1.10) for ischaemic stroke, 0.90 (0.72 to 1.11) for acute myocardial infarction, 0.88 (0.67 to 1.16) for venous thromboembolism, and 0.87 (0.70 to 1.07) for congestive heart failure). Similarly, a secondary analysis of exclusive users of bevacizumab or ranibizumab showed no differences in risk between the two drugs (adjusted odds ratios for bevacizumab relative to ranibizumab of 1.03 (0.67 to 1.60) for ischaemic stroke, 1.23 (0.85 to 1.77) for acute myocardial infarction, 0.92 (0.51 to 1.69) for venous thromboembolism, and

  6. Prognostic value of blood glucose in emergency room and glycosylated hemoglobin in patients who have suffered an acute cerebro-vascular event.

    PubMed

    Ernaga Lorea, Ander; Hernández Morhain, María Cecilia; Ollero García-Agulló, María Dolores; Martínez de Esteban, Juan Pablo; Iriarte Beroiz, Ana; Gállego Culleré, Jaime

    2017-07-07

    Stress hyperglycemia has been associated with a worse prognosis in patients hospitalized in critical care units. The aim of this study is to evaluate the impact of blood glucose and glycosylated hemoglobin (HbA1c) levels on the mortality of patients suffering a acute cerebro-vascular event, and to determine if this relationship depends on the presence of diabetes. A retrospective analysis of 255 patients admitted to the ER for stroke was performed. Venous plasma glucose levels in the emergency room and HbA1c levels within the first 48hours were analyzed. The presence of diabetes was defined in terms of the patients' medical history, as well as their levels of fasting plasma glucose and HbA1c. Mortality was assessed within the first 30 months after the onset of the acute event. 28.2% of patients had diabetes. Higher mortality was observed in patients who had been admitted with plasma glucose levels≥140mg/dl (hazard ratio [HR]=2.22, 95% CI: 1.18-4.16, P=.013) after adjusting for various factors. This relationship was not confirmed in diabetic patients (HR=2.20, 95% CI: 0.66-7.40, P=.201) and was in non-diabetics (HR=2.55, 95% CI: 1.11-5.85, P=.027). In diabetics, HbA1c≥7% was not associated with poor prognosis (HR=0.68, 95% CI: 0.23-1.98, P=.475), whereas non-diabetics with admission levels of HbA1c falling within the pre-diabetes range (5.7% -6.4%) had a higher mortality (HR=2.62, 95% CI: 1.01-6.79, P=.048). Admission hyperglycemia is associated with a worse prognosis in patients without diabetes admitted for stroke, but this relationship was not seen in diabetics. In non-diabetic patients, HbA1c levels in the pre-diabetes range is associated with higher mortality. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  7. Age-related ventricular-vascular coupling during acute inflammation in humans: Effect of physical activity.

    PubMed

    Lane, Abbi D; Kappus, Rebecca M; Bunsawat, Kanokwan; Ranadive, Sushant M; Yan, Huimin; Phillips, Shane; Baynard, Tracy; Woods, Jeffrey A; Motl, Robert; Fernhall, Bo

    2015-07-01

    Aging is commonly accompanied by increased arterial and ventricular stiffness (determined by arterial elastance (Ea) and ventricular elastance (Elv)), augmented ventricular-vascular coupling ratios (Ea/Elv) and systemic inflammation. Acute inflammation may impact ventricular-vascular coupling and predispose older adults to cardiovascular events. However, physically active older adults have more compliant large arteries and left ventricles and lower inflammation than sedentary older adults. We hypothesized that acute inflammation would alter Ea, Elv, and Ea/Elv more in older versus younger adults but that higher levels of physical activity would attenuate inflammation-induced changes. End-systolic and central blood pressures were obtained using applanation tonometry before and at 24 and 48 h post-influenza vaccination in 24 older and 38 younger adults. Ultrasonography was used to measure ventricular volumes and other indices of cardiac performance. Physical activity was measured with accelerometry. Ea and Ea/Elv were maintained (p > 0.05), but Elv was reduced (p < 0.05) 24 h post-inflammation. Other indices of systolic performance were reduced in older but not younger adults; diastolic performance was attenuated in both groups 24 h post-inflammation (p < 0.05 for all). Older, but not younger, adults decreased central pressure during inflammation (p < 0.05). When controlled for age, physical activity was not related to the inflammation-induced changes in elastance (p > 0.05) except in the most active group of seniors (p < 0.05). Aging did not affect the elastance responses but did affect central blood pressure and other ventricular systolic responses to acute inflammation. Aging, not physical activity, appears to modulate cardiovascular responses to acute inflammation, except in the most active older adults. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  8. Risk stratification for the development of respiratory adverse events following vascular surgery using the Society of Vascular Surgery's Vascular Quality Initiative.

    PubMed

    Genovese, Elizabeth A; Fish, Larry; Chaer, Rabih A; Makaroun, Michel S; Baril, Donald T

    2017-02-01

    Postoperative respiratory adverse events (RAEs) are associated with high rates of morbidity and mortality in general surgery, however, little is known about these complications in the vascular surgery population, a frail subset with multiple comorbidities. The objective of this study was to describe the contemporary incidence of RAEs in vascular surgery patients, the risk factors for this complication, and the overall impact of RAEs on patient outcomes. The Vascular Quality Initiative was queried (2003-2014) for patients who underwent endovascular abdominal aortic repair, open abdominal aortic aneurysm repair, thoracic endovascular aortic repair, suprainguinal bypass, or infrainguinal bypass. A mixed-effects logistic regression model determined the independent risk factors for RAEs. Using a random 85% of the cohort, a risk prediction score for RAEs was created, and the score was validated using the remaining 15% of the cohort, comparing the predicted to the actual incidence of RAE and determining the area under the receiver operating characteristic curve. The independent risk of in-hospital mortality and discharge to a nursing facility associated with RAEs was determined using a mixed-effects logistic regression to control for baseline patient characteristics, operative variables, and other postoperative adverse events. The cohort consisted of 52,562 patients, with a 5.4% incidence of RAEs. The highest rates of RAEs were seen in current smokers (6.1%), recent acute myocardial infarction (10.1%), symptomatic congestive heart failure (9.9%), chronic obstructive pulmonary disease requiring oxygen therapy (11.0%), urgent and emergent procedures (6.4% and 25.9%, respectively), open abdominal aortic aneurysm repairs (17.6%), in situ suprainguinal bypasses (9.68%), and thoracic endovascular aortic repairs (9.6%). The variables included in the risk prediction score were age, body mass index, smoking status, congestive heart failure severity, chronic obstructive pulmonary

  9. Effect of long-term hydroxychloroquine on vascular events in patients with systemic lupus erythematosus: a database prospective cohort study.

    PubMed

    Hsu, Chung-Yuan; Lin, Yu-Sheng; Su, Yu-Jih; Lin, Hsing-Fen; Lin, Ming-Shyan; Syu, Ya-Jhu; Cheng, Tien-Tsai; Yu, Shan-Fu; Chen, Jia-Feng; Chen, Tien-Hsing

    2017-12-01

    The incidence of thromboembolism in patients with SLE is higher than that in the general population. HCQ, widely used to treat lupus, may have vascular protective effects. The aim of this study was to determine whether long-term HCQ exposure is associated with decreased thromboembolism risk in SLE. We designed a prospective cohort study within an SLE population based on the National Health Insurance Research Database in Taiwan. We divided participants into HCQ and control groups according to HCQ prescription during the first year. These groups were defined by medication possession ratio (MPR) ⩾80% and MPR = 0%, respectively. Patients with an MPR between 0 and 80% were excluded. The primary outcome was a composite vascular event, including acute coronary syndrome, ischaemic stroke, pulmonary embolism, deep vein thrombosis and peripheral arterial disease 1 year after inclusion. We excluded patients from the cohort if they had outcomes within the first year. A total of 8397 patients were eligible for analysis. After propensity-score matching, we included 1946 patients in each group. During a mean follow-up of 7.4 years, the number of events was 139 in the HCQ group (7.1%) and 149 in the control group (7.7%). The risk of vascular events in the HCQ group was similar to that in the control group (hazard ratio = 0.91; 95% CI: 0.72, 1.15). Further subgroup analyses confirmed no statistically significant differences between the groups. Long-term HCQ appears to have no vascular protective effect in patients with SLE. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  10. The relationship between duration of psoriasis, vascular inflammation, and cardiovascular events.

    PubMed

    Egeberg, Alexander; Skov, Lone; Joshi, Aditya A; Mallbris, Lotus; Gislason, Gunnar H; Wu, Jashin J; Rodante, Justin; Lerman, Joseph B; Ahlman, Mark A; Gelfand, Joel M; Mehta, Nehal N

    2017-10-01

    Psoriasis is associated with risk of cardiovascular (CV) disease (CVD) and a major adverse CV event (MACE). Whether psoriasis duration affects risk of vascular inflammation and MACEs has not been well characterized. We utilized two resources to understand the effect of psoriasis duration on vascular disease and CV events: (1) a human imaging study and (2) a population-based study of CVD events. First, patients with psoriasis (N = 190) underwent fludeoxyglucose F 18 positron emission tomography/computed tomography (duration effect reported as a β-coefficient). Second, MACE risk was examined by using nationwide registries (adjusted hazard ratios in patients with psoriasis (n = 87,161) versus the general population (n = 4,234,793). In the human imaging study, patients were young, of low CV risk by traditional risk scores, and had a high prevalence of cardiometabolic diseases. Vascular inflammation by fludeoxyglucose F 18 positron emission tomography/computed tomography was significantly associated with disease duration (β = 0.171, P = .002). In the population-based study, psoriasis duration had strong relationship with MACE risk (1.0% per additional year of psoriasis duration [hazard ratio, 1.010; 95% confidence interval, 1.007-1.013]). These studies utilized observational data. We found detrimental effects of psoriasis duration on vascular inflammation and MACE, suggesting that cumulative duration of exposure to low-grade chronic inflammation may accelerate vascular disease development and MACEs. Providers should consider inquiring about duration of disease to counsel for heightened CVD risk in psoriasis. Copyright © 2017 American Academy of Dermatology, Inc. All rights reserved.

  11. Association between homocyst(e)ine levels and risk of vascular events.

    PubMed

    Kaplan, Eugene D

    2003-03-01

    Homocyst(e)ine is a novel risk factor in vascular disease. First observations of vascular lesions in children with high blood homocyst(e)ine levels due to severe inborn enzyme deficiencies led to the hypothesis that elevated blood homocyst(e)ine levels might be a risk factor for vascular disease. A substantial body of evidence on the role of the homocyst(e)ine in the development of coronary and carotid artery disease, myocardial infarction, stroke, deep vein thrombosis and other disorders has been accumulated over the last 30 years. Cross-sectional and case-control studies provide initial and the strongest support for the hypothesis, followed by results from the prospective cohorts. Infrequent cases of homozygous mutations of the key enzymes in the homocyst(e)ine metabolism chain are able to produce extreme homocyst(e)inemia and early vascular lesions. More frequently, heterozygous enzyme mutations and deficiencies of folate and vitamins B6 and B12 cause mild to moderate homocyst(e)inemia, which is still strongly associated with the increased risk of vascular events. Elevated homocyst(e)ine levels may be effectively managed with adequate folate, B12 and B6 intake in doses comparable to or above FDA recommendations. Whether correction of elevated homocyst(e)ine levels with vitamins is helpful in prevention and treatment of vascular events remains unknown and is under investigation in ongoing clinical trials (VISP, VITATOPS). No consensus on homocyst(e)ine management is available at the present time.

  12. Vascular capacitance and cardiac output in pacing-induced canine models of acute and chronic heart failure.

    PubMed

    Ogilvie, R I; Zborowska-Sluis, D

    1995-11-01

    The relationship between stressed and total blood volume, total vascular capacitance, central blood volume, cardiac output (CO), and pulmonary capillary wedge pressure (Ppcw) was investigated in pacing-induced acute and chronic heart failure. Acute heart failure was induced in anesthetized splenectomized dogs by a volume load (20 mL/kg over 10 min) during rapid right ventricular pacing at 250 beats/min (RRVP) for 60 min. Chronic heart failure was induced by continuous RRVP for 2-6 weeks (average 24 +/- 2 days). Total vascular compliance and capacitance were calculated from the mean circulatory filling pressure (Pmcf) during transient circulatory arrest after acetylcholine at three different circulating volumes. Stressed blood volume was calculated as a product of compliance and Pmcf, with the total blood volume measured by a dye dilution. Central blood volume (CBV) and CO were measured by thermodilution. Central (heart and lung) vascular capacitance was estimated from the plot of Ppcw against CBV. Acute volume loading without RRVP increased capacitance and CO, whereas after volume loading with RRVP, capacitance and CO were unaltered from baseline. Chronic RRVP reduced capacitance and CO. All interventions, volume +/- RRVP or chronic RRVP, increased stressed and central blood volumes and Ppcw. Acute or chronic RRVP reduced central vascular capacitance. Cardiac output was increased when stressed and unstressed blood volumes increased proportionately as during volume loading alone. When CO was reduced and Ppcw increased, as during chronic RRVP or acute RRVP plus a volume load, stressed blood volume was increased and unstressed blood volume was decreased. Thus, interventions that reduced CO and increased Ppcw also increased stressed and reduced unstressed blood volume and total vascular capacitance.

  13. One-year atherothrombotic vascular events rates in outpatients with recent non-cardioembolic ischemic stroke: the EVEREST (Effective Vascular Event REduction after STroke) registry.

    PubMed

    Suzuki, Norihiro; Sato, Motoki; Houkin, Kiyohiro; Terayama, Yasuo; Uchiyama, Shinichiro; Daida, Hiroyuki; Shigematsu, Hiroshi; Goto, Shinya; Tanaka, Kortaro; Origasa, Hideki; Miyamoto, Susumu; Minematsu, Kazuo; Matsumoto, Masayasu; Okada, Yasushi

    2012-05-01

    Patients with recent ischemic stroke may have higher risk of atherothrombosis than stable patients with established vascular events. Our aims were to investigate 1-year atherothrombotic vascular event rates and to assess the risk factors for recurrent ischemic stroke in this population. This prospective cohort study was conducted between January 2007 and July 2009 at 313 hospitals in Japan. Outpatients who were at least 45 years of age and who had received oral antiplatelet therapy were enrolled within 2 weeks to 6 months from the last onset of noncardioembolic ischemic stroke. At 12 ± 3 months after enrollment, data on presence/absence of atherothrombotic vascular events were collected. The primary endpoint was the occurrence of fatal or nonfatal ischemic stroke. A total of 3452 patients were enrolled, and 3411 patients who had baseline data were included in the analysis. The 1-year event rate was 3.81% (95% confidence interval 3.15-4.48%) for fatal or nonfatal ischemic stroke and 0.84% (95% confidence interval 0.52-1.15%) for all-cause mortality. The annual rate of recurrent ischemic stroke was significantly higher in patients who had ischemic stroke at least twice than in patients who had first-ever ischemic stroke (5.02% vs 3.59%; P = .0313). In the multivariable Cox regression analysis, recurrent ischemic stroke was significantly associated with age (P = .0033), the presence of diabetes (P = .0129), and waist circumference ≥80 cm (P = .0056). Patients with recent ischemic stroke have a higher risk of stroke recurrence than stable patients enrolled in the REduction of Atherothrombosis for Continued Health (REACH) registry even though they received antiplatelet therapy. The rigorous management of risk factors is needed. Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  14. Acute vascular effects of waterpipe smoking: Importance of physical activity and fitness status.

    PubMed

    Alomari, Mahmoud A; Khabour, Omar F; Alzoubi, Karem H; Shqair, Dana M; Stoner, Lee

    2015-06-01

    While new forms of tobacco, including waterpipe (WP) smoking, continue to gain popularity, limited literature has examined the vascular health consequences. The purpose of the current study was to examine: (i) the acute WP-induced changes in vascular function; (ii) whether acute changes in vascular function are modified by lifestyle behaviors (habitual physical activity, physical fitness). Fifty three (22.7 y, 36% F, 23.4 kg/m(2)) otherwise healthy WP smokers were recruited. Strain-gauge plethysmography was used to measure forearm blood flow, vascular resistance, venous capacitance, and venous outflow at rest and following occlusion. Habitual physical activity was determined using the Arabic version of short-form international physical activity questionnaire, while physical fitness was assessed using the 6 min walk test and handgrip strength. Partial correlations were used to examine the relationships between post-smoking vascular function and lifestyle behaviors, controlling for pre-smoking vascular measures. (i) WP had a small effect on forearm post-occlusion blood flow (d = -0.19), a moderate effect on venous outflow (d = 0.30), and a moderate effect on post-occlusion vascular resistance (d = 0.32). (ii) Total habitual physical activity strongly correlated with resting blood flow (r = 0.50) and moderately with vascular resistance (r = -0.40). Handgrip strength moderately correlated with venous capacitance (r = 0.30) and post-occlusion blood flow (r = 0.30), while 6 min walked distance moderately correlated with resting venous capacitance (r = 0.30). Waterpipe smoking is associated with immediate changes in vascular function, which are exacerbated in individuals with low habitual physical activity and physical fitness levels in young otherwise healthy individuals. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Risk Stratification for the Development of Respiratory Adverse Events Following Vascular Surgery Using the Society of Vascular Surgery’s Vascular Quality Initiative

    PubMed Central

    Genovese, Elizabeth A; Fish, Larry; Chaer, Rabih A; Makaroun, Michel S; Baril, Donald T

    2017-01-01

    Objective Post-operative respiratory adverse events (RAEs) are associated with high rates of morbidity and mortality in general surgery, however little is known about these complications in the vascular surgery population, a frail subset with multiple comorbidities. The objective of this study was to describe the contemporary incidence of RAEs in vascular surgery patients, the risk factors for this complication and the overall impact of RAEs on patient outcomes. Methods The Vascular Quality Initiative was queried (2003–2014) for patients who underwent endovascular abdominal aortic repair, open abdominal aortic aneurysm (AAA) repair, thoracic endovascular aortic repair (TEVAR), suprainguinal bypass or infrainguinal bypass. A mixed-effects logistic regression model determined the independent risk factors for RAEs. Using a random 85% of the cohort, a risk prediction score for RAEs was created and the score was validated using the remaining 15% of the cohort, comparing the predicted to the actual incidence of RAE and determining the area under the receiver operating characteristic curve. The independent risk of in-hospital mortality and discharge to a nursing facility associated with RAEs was determined using a mixed-effects logistic regression to control for baseline patient characteristics, operative variables and other post-operative adverse events. Results The cohort consisted of 52,562 patients, with a 5.4% incidence of RAEs. The highest rates of RAEs were seen in current smokers (6.1%), recent acute myocardial infarction (10.1%), symptomatic congestive heart failure (CHF) (9.9%), chronic obstructive pulmonary disease (COPD) requiring oxygen therapy (11.0%), urgent and emergent procedures (6.4% and 25.9%, respectively), open AAA repairs (17.6%), in-situ suprainguinal bypasses (9.68%) and TEVARs (9.6%). The variables included in the risk prediction score were age, body mass index, smoking status, CHF severity, COPD severity, degree of renal insufficiency

  16. Vascular events in Korean patients with myeloproliferative neoplasms and their relationship to JAK2 mutation.

    PubMed

    Bang, Soo-Mee; Lee, Jong-Seok; Ahn, Jeong Yeal; Lee, Jae Hoon; Hyun, Myung Soo; Kim, Bong Seog; Park, Moo Rim; Chi, Hyun-Sook; Kim, Ho Young; Kim, Hyo Jung; Lee, Moon Hee; Kim, Hwak; Won, Jong Ho; Yoon, Hwi Joong; Oh, Do-Yeun; Nam, Eun-Mi; Bae, Sung Hwa; Kim, Byoung-Kook

    2009-03-01

    Evaluation of the Janus kinase 2 (JAK2) V617F mutation has been widely used for the diagnosis of myeloproliferative neoplasms (MPN). However, its prognostic relevance to clinical outcome is not completely understood. We investigated the association of JAK2 V617F with vascular events in Korean patients with myeloproliferative neoplasms (MPN). We studied 283 patients from 15 centers, who were diagnosed with MPN. The JAK2 V617F status was evaluated by allele-specific polymerase chain reaction (PCR) and sequencing. The patients' diagnoses were essential thrombocythemia (ET n = 146), polycythemia vera (PV n = 120), primary myelofibrosis (n = 12), and unclassifiable MPN (MPNu n = 5). JAK2 V617F was detected in 89 (61%) patients with ET, 103 (86%) with PV, four (33%) with myelofibrosis, and four (80%) with MPNu. A higher number of leukocytes, haemoglobin levels and BM cellularity as well as an older age, lower platelet counts, and diagnosis of PV were significantly correlated with JAK2 V617F. Eighty-three and 43 episodes of thrombosis and bleeding occurred in 100 patients each before and after the diagnosis. Vascular events more frequently occurred in 37% of patients with JAK2 V617F than in 29% of those without the mutation (p = 0.045). Among 175 patients whose samples were available for sequencing, 28 patients with homozygous JAK2 V617F had vascular events more frequently (57%) than those who were heterozygotes (39%) or had the wild type (27%) (p = 0.03). The multivariate analysis showed that a JAK2 homozygous mutation, hypercholesterolemia and older age were independent risk factors for a vascular event. The results of this study showed that Korean patients with MPN had a similar JAK2 mutation rate and frequency of vascular events when compared to Western patients. The presence of V617F was significantly related to vascular events. Therefore, initial evaluation for the JAK2 mutation and careful monitoring for vascular events should be performed in MPN patients.

  17. Acute mesenteric ischemia: a vascular emergency.

    PubMed

    Klar, Ernst; Rahmanian, Parwis B; Bücker, Arno; Hauenstein, Karlheinz; Jauch, Karl-Walter; Luther, Bernd

    2012-04-01

    Acute mesenteric ischemia is still fatal in 50% to 70% of cases. This consensus paper was written with the participation of physicians from all of the involved specialties for the purpose of improving outcomes. Mesenteric ischemia must be recognized as a vascular emergency requiring rapid and efficient clinical evaluation and treatment. We reviewed pertinent literature that was retrieved by a PubMed search on the terms "mesenteric ischemia" AND "arterial" OR "venous" OR "clinical presentation" OR "diagnosis" OR "therapy" OR "surgery" OR " interventional radiology." Our review also took account of the existing guidelines of the American College of Cardiology/American Heart Association. Intensive discussions among the participating physicians, representing all of the specialties involved in the management of mesenteric ischemia, led to the creation of this interdisciplinary paper. Biphasic contrast-enhanced computerized tomography is the diagnostic tool of choice for the detection of arterial or venous occlusion. If non-occlusive mesenteric ischemia is suspected, angiography should be performed, with the option of intraarterial pharmacotherapy to induce local vasodilation. Endovascular techniques have become increasingly important in the treatment of arterial occlusion. Embolic central mesenteric artery occlusion requires surgical treatment; surgery is also needed in case of peritonitis. Portal-vein thrombosis can be treated by local thrombolysis through a transhepatically placed catheter. This should be done within 3 to 4 weeks of the event to prevent later complications of portal hypertension. Rapid diagnosis (within 4 to 6 hours of symptom onset) and interdisciplinary cooperation in the provision of treatment are required if the poor outcome of this condition is to be improved.

  18. Risk Factors for Vascular Occlusive Events and Death Due to Bleeding in Trauma Patients; an Analysis of the CRASH-2 Cohort

    PubMed Central

    Pealing, Louise; Perel, Pablo; Prieto-Merino, David; Roberts, Ian

    2012-01-01

    Background Vascular occlusive events can complicate recovery following trauma. We examined risk factors for venous and arterial vascular occlusive events in trauma patients and the extent to which the risk of vascular occlusive events varies with the severity of bleeding. Methods and Findings We conducted a cohort analysis using data from a large international, double-blind, randomised, placebo-controlled trial (The CRASH-2 trial) [1]. We studied the association between patient demographic and physiological parameters at hospital admission and the risk of vascular occlusive events. To assess the extent to which risk of vascular occlusive events varies with severity of bleeding, we constructed a prognostic model for the risk of death due to bleeding and assessed the relationship between risk of death due to bleeding and risk of vascular occlusive events. There were 20,127 trauma patients with outcome data including 204 (1.01%) patients with a venous event (pulmonary embolism or deep vein thrombosis) and 200 (0.99%) with an arterial event (myocardial infarction or stroke). There were 81 deaths due to vascular occlusive events. Increasing age, decreasing systolic blood pressure, increased respiratory rates, longer central capillary refill times, higher heart rates and lower Glasgow Coma Scores (all p<0.02) were strong risk factors for venous and arterial vascular occlusive events. Patients with more severe bleeding as assessed by predicted risk of haemorrhage death had a greatly increased risk for all types of vascular occlusive event (all p<0.001). Conclusions Patients with severe traumatic bleeding are at greatly increased risk of venous and arterial vascular occlusive events. Older age and blunt trauma are also risk factors for vascular occlusive events. Effective treatment of bleeding may reduce venous and arterial vascular occlusive complications in trauma patients. PMID:23251374

  19. Prediction of vascular abnormalities on CT angiography in patients with acute headache.

    PubMed

    Alons, Imanda M E; Goudsmit, Ben F J; Jellema, Korné; van Walderveen, Marianne A A; Wermer, Marieke J H; Algra, Ale

    2018-05-09

    Patients with acute headache increasingly undergo CT-angiography (CTA) to evaluate underlying vascular causes. The aim of this study is to determine clinical and non-contrast CT (NCCT) criteria to select patients who might benefit from CTA. We retrospectively included patients with acute headache who presented to the emergency department of an academic medical center and large regional teaching hospital and underwent NCCT and CTA. We identified factors that increased the probability of finding a vascular abnormality on CTA, performed multivariable regression analyses and determined discrimination with the c-statistic. A total of 384 patients underwent NCCT and CTA due to acute headache. NCCT was abnormal in 194 patients. Among these, we found abnormalities in 116 cases of which 99 aneurysms. In the remaining 190 with normal NCCT we found abnormalities in 12 cases; four unruptured aneurysms, three cerebral venous thrombosis', two reversible cerebral vasoconstriction syndromes, two cervical arterial dissections and one cerebellar infarction. In multivariable analysis abnormal NCCT, lowered consciousness and presentation within 6 hr of headache onset were independently associated with abnormal CTA. The c-statistic of abnormal NCCT alone was 0.80 (95% CI: 0.75-0.80), that also including the other two variables was 0.84 (95% CI: 0.80-0.88). If NCCT was normal no other factors could help identify patients at risk for abnormalities. In patients with acute headache abnormal NCCT is the strongest predictor of a vascular abnormality on CTA. If NCCT is normal no other predictors increase the probability of finding an abnormality on CTA and diagnostic yield is low. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

  20. Vascular Access System for Continuous Arterial Infusion of a Protease Inhibitor in Acute Necrotizing Pancreatitis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ganaha, Fumikiyo; Yamada, Tetsuhisa; Yorozu, Naoya

    1999-09-15

    We used a vascular access system (VAS) for continuous arterial infusion (CAI) of a protease inhibitor in two patients with acute necrotizing pancreatitis. The infusion catheter was placed into the dorsal pancreatic artery in the first patient and into the gastroduodenal artery in the second, via a femoral artery approach. An implantable port was then connected to the catheter and was secured in a subcutaneous pocket prepared in the right lower abdomen. No complications related to the VAS were encountered. This system provided safe and uncontaminated vascular access for successful CAI for acute pancreatitis.

  1. Ophthalmic Vascular Events after Primary Unilateral Intra-arterial Chemotherapy for Retinoblastoma in Early and Recent Eras.

    PubMed

    Dalvin, Lauren A; Ancona-Lezama, David; Lucio-Alvarez, J Antonio; Masoomian, Babak; Jabbour, Pascal; Shields, Carol L

    2018-06-16

    To assess risk factors for ophthalmic vascular events after intra-arterial chemotherapy (IAC) for retinoblastoma. Retrospective cohort study. Patients who received unilateral IAC as primary treatment for retinoblastoma from January 1, 2009, to November 30, 2017, at a single center. Records were reviewed for patient demographics, tumor features, IAC parameters, and treatment-related vascular events in the early IAC era (2009-2011) compared with the recent era (2012-2017) using the t test and Fisher exact test. Change in event rates over time was assessed using Poisson regression analysis, with Spearman's rho used to test correlation. Rate of IAC-induced ophthalmic vascular events. There were 243 chemotherapy infusions in 76 eyes of 76 patients, divided into early (22 eyes, 57 infusions) and recent (54 eyes, 186 infusions) eras. Intra-arterial chemotherapy consisted of melphalan (243 infusions), topotecan (124 infusions), and carboplatin (9 infusions). A comparison (early vs. recent era) revealed fewer mean number of infusions (2.6 vs. 3.4, P = 0.02) with similar mean patient age and presenting tumor features. Event rates decreased over time (P < 0.01), with fewer ophthalmic vascular events (early era vs. recent era) in the recent era (59% vs. 9% per eye, 23% vs. 3% per infusion, P < 0.01), including peripheral retinal nonperfusion (5% vs. 2% per eye, P = 0.50), vitreous hemorrhage (9% vs. 2%, P = 0.20), subretinal hemorrhage (0% vs. 2%, P = 0.99), branch retinal vein occlusion (5% vs. 0%, P = 0.29), choroidal ischemia (14% vs. 4%, P = 0.14), and ophthalmic artery spasm/occlusion (27% vs. 0%, P < 0.01). Events did not correlate to patient age (P = 0.75), tumor diameter (P = 0.32), tumor thickness (P = 0.59), or cumulative dosage of melphalan (P = 0.13) or topotecan (P = 0.59). There were no IAC-induced vascular events in 72 infusions of 21 consecutively treated eyes in 2016 to 2017. Ophthalmic vascular events after IAC have decreased from the early era

  2. Withdrawal of statins increases event rates in patients with acute coronary syndromes.

    PubMed

    Heeschen, Christopher; Hamm, Christian W; Laufs, Ulrich; Snapinn, Steven; Böhm, Michael; White, Harvey D

    2002-03-26

    HMG-CoA Reductase Inhibitors (statins) reduce cardiac event rates in patients with stable coronary heart disease. Withdrawal of chronic statin treatment during acute coronary syndromes may impair vascular function independent of lipid-lowering effects and thus increase cardiac event rate. We investigated the effects of statins on the cardiac event rate in 1616 patients of the Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) study who had coronary artery disease and chest pain in the previous 24 hours. We recorded death and nonfatal myocardial infarction during the 30-day follow-up. Baseline clinical characteristics did not differ among 1249 patients without statin therapy, 379 patients with continued statin therapy, and 86 patients with discontinued statin therapy after hospitalization. Statin therapy was associated with a reduced event rate at 30-day follow-up compared with patients without statins (adjusted hazard ratio, 0.49 [95% CI, 0.21 to 0.86]; P=0.004). If the statin therapy was withdrawn after admission, cardiac risk increased compared with patients who continued to receive statins (2.93 [95% CI, 1.64 to 6.27]; P=0.005) and tended to be higher compared with patients who never received statins (1.69 [95% CI, 0.92 to 3.56]; P=0.15). This was related to an increased event rate during the first week after onset of symptoms and was independent of cholesterol levels. In a multivariate model, troponin T elevation (P=0.005), ST changes (P=0.02), and continuation of statin therapy (P=0.008) were the only independent predictors of patient outcome. Statin pretreatment in patients with acute coronary syndromes is associated with improved clinical outcome. However, discontinuation of statins after onset of symptoms completely abrogates this beneficial effect.

  3. Impaired sympathetic vascular regulation in humans after acute dynamic exercise

    NASA Technical Reports Server (NTRS)

    Halliwill, J. R.; Taylor, J. A.; Eckberg, D. L.

    1996-01-01

    1. The reduction in vascular resistance which accompanies acute dynamic exercise does not subside immediately during recovery, resulting in a post-exercise hypotension. This sustained vasodilatation suggests that sympathetic vascular regulation is altered after exercise. 2. Therefore, we assessed the baroreflex control of sympathetic outflow in response to arterial pressure changes, and transduction of sympathetic activity into vascular resistance during a sympatho-excitatory stimulus (isometric handgrip exercise) after either exercise (60 min cycling at 60% peak aerobic power (VO2,peak)) or sham treatment (60 min seated rest) in nine healthy subjects. 3. Both muscle sympathetic nerve activity and calf vascular resistance were reduced after exercise (-29.7 +/- 8.8 and -25.3 +/- 9.1%, both P < 0.05). The baroreflex relation between diastolic pressure and sympathetic outflow was shifted downward after exercise (post-exercise intercept, 218 +/- 38 total integrated activity (heartbeat)-1; post-sham intercept, 318 +/- 51 total integrated activity (heartbeat)-1, P < 0.05), indicating less sympathetic outflow across all diastolic pressures. Further, the relation between sympathetic activity and vascular resistance was attenuated after exercise (post-exercise slope, 0.0031 +/- 0.0007 units (total integrated activity)-1 min; post-sham slope, 0.0100 +/- 0.0033 units (total integrated activity)-1 min, P < 0.05), indicating less vasoconstriction with any increase in sympathetic activity. 4. Thus, both baroreflex control of sympathetic outflow and the transduction of sympathetic activity into vascular resistance are altered after dynamic exercise. We conclude that the vasodilation which underlies post-exercise hypotension results from both neural and vascular phenomena.

  4. Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes

    PubMed Central

    Kelly-Cobbs, Aisha I.; Prakash, Roshini; Li, Weiguo; Pillai, Bindu; Hafez, Sherif; Coucha, Maha; Johnson, Maribeth H.; Ogbi, Safia N.; Fagan, Susan C.

    2013-01-01

    Hemorrhagic transformation is an important complication of acute ischemic stroke, particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator, the only approved drug for the treatment of acute ischemic stroke. The objective of the present study was to determine the effects of acute manipulation of potential targets for vascular protection [i.e., NF-κB, peroxynitrite, and matrix metalloproteinases (MMPs)] on vascular injury and functional outcome in a diabetic model of cerebral ischemia. Ischemia was induced by middle cerebral artery occlusion in control and type 2 diabetic Goto-Kakizaki rats. Treatment groups received a single dose of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), the nonspecific NF-κB inhibitor curcumin, or the broad-spectrum MMP inhibitor minocycline at reperfusion. Poststroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated. All acute treatments reduced MMP-9 and hemorrhagic transformation in diabetic groups. In addition, acute curcumin and minocycline therapy reduced edema in these animals. Improved neurological function was observed in varying degrees with treatment, as indicated by beam-walk performance, modified Bederson scores, and grip strength; however, infarct size was similar to untreated diabetic animals. In control animals, all treatments reduced MMP-9 activity, yet bleeding was not improved. Neuroprotection was only conferred by curcumin and minocycline. Uncovering the underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies. PMID:23335797

  5. Injuries to the vascular endothelium: vascular wall and endothelial dysfunction.

    PubMed

    Fisher, Mark

    2008-01-01

    Vascular endothelial injury has multiple elements, and this article focuses on ischemia-related processes that have particular relevance to ischemic stroke. Distinctions between necrotic and apoptotic cell death provide a basic science context in which to better understand the significance of classical core and penumbra concepts of acute stroke, with apoptotic processes particularly prominent in the penumbra. The mitochondria are understood to serve as a reservoir of proteins that mediate apoptosis. Oxidative stress pathways generating reactive oxygen species (ROS) are prominent in endothelial injury, both ischemic and nonischemic, with prominent roles of enzyme- and nonenzymemediated pathways; mitochondria once again have a critical role, particularly in the nonenzymatic pathways generating ROS. Inflammation also contributes to vascular endothelial injury, and endothelial cells have the capacity to rapidly increase expression of inflammatory mediators following ischemic challenge; this leads to enhanced leukocyte-endothelial interactions mediated by selectins and adhesion molecules. Preconditioning consists of a minor version of an injurious event, which in turn may protect vascular endothelium from injury following a more substantial event. Presence of the blood-brain barrier creates unique responses to endothelial injury, with permeability changes due to impairment of endothelial-matrix interactions compounding altered vasomotor tone and tissue perfusion mediated by nitric oxide. Pharmacological protection against vascular endothelial injury can be provided by several of the phosphodiesterases (cilostazol and dipyridamole), along with statins. Optimal clinical responses for protection of brain vascular endothelium may use preconditioning as a model, and will likely require combined protection against apoptosis, ROS, and inflammation.

  6. Quantification of vascular damage in acute kidney injury with fluorine magnetic resonance imaging and spectroscopy.

    PubMed

    Moore, Jeremy K; Chen, Junjie; Pan, Hua; Gaut, Joseph P; Jain, Sanjay; Wickline, Samuel A

    2018-06-01

    To design a fluorine MRI/MR spectroscopy approach to quantify renal vascular damage after ischemia-reperfusion injury, and the therapeutic response to antithrombin nanoparticles (NPs) to protect kidney function. A total of 53 rats underwent 45 min of bilateral renal artery occlusion and were treated at reperfusion with either plain perfluorocarbon NPs or NPs functionalized with a direct thrombin inhibitor (PPACK:phenyalanine-proline-arginine-chloromethylketone). Three hours after reperfusion, kidneys underwent ex vivo fluorine MRI/MR spectroscopy at 4.7 T to quantify the extent and volume of trapped NPs, as an index of vascular damage and ischemia-reperfusion injury. Microscopic evaluation of structural damage and NP trapping in non-reperfused renal segments was performed. Serum creatinine was quantified serially over 7 days. The damaged renal cortico-medullary junction trapped a significant volume of NPs (P = 0.04), which correlated linearly (r = 0.64) with the severity of kidney injury 3 h after reperfusion. Despite global large vessel reperfusion, non-reperfusion in medullary peritubular capillaries was confirmed by MRI and microscopy, indicative of continuing hypoxia due to vascular compromise. Treatment of animals with PPACK NPs after acute kidney injury did not accelerate kidney functional recovery. Quantification of ischemia-reperfusion injury after acute kidney injury with fluorine MRI/MR spectroscopy of perfluorocarbon NPs objectively depicts the extent and severity of vascular injury and its linear relationship to renal dysfunction. The lack of kidney function improvement after early posttreatment thrombin inhibition confirms the rapid onset of ischemia-reperfusion injury as a consequence of vascular damage and non-reperfusion. The prolongation of medullary ischemia renders cortico-medullary tubular structures susceptible to continued necrosis despite restoration of large vessel flow, which suggests limitations to acute interventions after

  7. Copeptin and Long-Term Risk of Recurrent Vascular Events After Transient Ischemic Attack and Ischemic Stroke: Population-Based Study.

    PubMed

    Greisenegger, Stefan; Segal, Helen C; Burgess, Annette I; Poole, Debbie L; Mehta, Ziyah; Rothwell, Peter M

    2015-11-01

    Copeptin, the c-terminal portion of provasopressin, is a useful prognostic marker in patients after myocardial infarction and heart failure. More recently, high levels of copeptin have also been associated with worse functional outcome and increased mortality within the first year after ischemic stroke and transient ischemic attack (TIA). However, to date, there are no published data on whether copeptin predicts long-term risk of vascular events after TIA and stroke. We measured copeptin levels in consecutive patients with TIA or ischemic stroke in a population-based study (Oxford Vascular Study) recruited from 2002 to 2007 and followed up to 2014. Associations with risk of recurrent vascular events were determined by Cox-regression. During ≈6000 patient-years in 1076 patients, there were 357 recurrent vascular events, including 174 ischemic strokes. After adjustment for age, sex, and risk factors, copeptin was predictive of recurrent vascular events (adjusted hazard ratio per SD, 1.47; 95% confidence interval, 1.31-1.64; P=0.0001), vascular death (1.85; 1.60-2.14; P<0.0001), all-cause death (1.75; 1.58-1.93; P<0.0001), and recurrent ischemic stroke (1.22; 1.04-1.44; P=0.017); and improved model-discrimination significantly: net reclassification improvement for recurrent vascular events (32%; P<0.0001), vascular death (55%; P<0.0001), death (66%; P<0.0001), and recurrent stroke (16%; P=0.044). The predictive value of copeptin was largest in patients with cardioembolic index events (adjusted hazard ratio, 1.84; 95% confidence interval, 1.53-2.20 versus 1.31, 1.14-1.50 in noncardioembolic stroke; P=0.0025). In patients with cardioembolic stroke, high copeptin levels were associated with a 4-fold increased risk of vascular events within the first year of follow-up (adjusted hazard ratio, 4.02; 95% confidence interval, 2.13-7.70). In patients with TIA and ischemic stroke, copeptin predicted recurrent vascular events and death, particularly after cardioembolic TIA

  8. Dual-phase CT for the assessment of acute vascular injuries in high-energy blunt trauma: the imaging findings and management implications.

    PubMed

    Iacobellis, Francesca; Ierardi, Anna M; Mazzei, Maria A; Magenta Biasina, Alberto; Carrafiello, Gianpaolo; Nicola, Refky; Scaglione, Mariano

    2016-01-01

    Acute vascular injuries are the second most common cause of fatalities in patients with multiple traumatic injuries; thus, prompt identification and management is essential for patient survival. Over the past few years, multidetector CT (MDCT) using dual-phase scanning protocol has become the imaging modality of choice in high-energy deceleration traumas. The objective of this article was to review the role of dual-phase MDCT in the identification and management of acute vascular injuries, particularly in the chest and abdomen following multiple traumatic injuries. In addition, this article will provide examples of MDCT features of acute vascular injuries with correlative surgical and interventional findings.

  9. Vascular Nitric Oxide-Superoxide Balance and Thrombus Formation after Acute Exercise.

    PubMed

    Przyborowski, Kamil; Proniewski, Bartosz; Czarny, Joanna; Smeda, Marta; Sitek, Barbara; Zakrzewska, Agnieszka; Zoladz, Jerzy A; Chlopicki, Stefan

    2018-02-21

    An acute bout of strenuous exercise in humans results in transient impairment of NO-dependent function, but it remains unknown whether this phenomenon is associated with increased risk of post-exercise thrombotic events. This study aimed to evaluate effects of a single bout of exhaustive running in mice on the balance of vascular nitric oxide (NO)/reactive oxygen species (ROS) production, and on thrombogenicity. At different time-points (0h, 2h and 4h) after exercise and in sedentary C57BL/6 mice the production of NO and superoxide (O2) in aorta was measured by electron paramagnetic resonance (EPR) spin trapping and by dihydroethidium (DHE)/HPLC-based method, respectively, while collagen-induced thrombus formation was analyzed in a microchip-based flow-chamber system (T-TAS). We also measured pre- and post-exercise plasma concentration of nitrite/nitrate and 6-keto-PGF1α. An acute bout of exhaustive running in mice resulted in decreased production of NO and increased production of O2 in aorta, with maximum changes 2h after completion of exercise when compared to sedentary mice. However, platelet thrombus formation was not changed by exercise as evidenced by unaltered time to start of thrombus formation (T10) and capillary occlusion (OT), and total thrombogenicity (AUC) as measured in a flow-chamber system. Strenuous exercise increased the plasma concentration of nitrite but did not affect nitrate and 6-keto-PGF1α concentrations. An acute bout of strenuous exercise in mice reduced NO and in parallel increased O2 production in aorta. This response was most pronounced 2h after exercise. Surprisingly, the reduced NO and increased O2 production did not result in increased post-exercise platelet-dependent thrombogenicity. These results show that transient reduction in NO bioavailability, caused by exercise-induced oxidative stress, does not modify post-exercise thromboresistance in healthy mice.

  10. Scabies in a bilateral hand allograft recipient: An additional mimicker of acute skin rejection in vascularized composite allotransplantation.

    PubMed

    Kanitakis, Jean; Morelon, Emmanuel

    2017-06-01

    Vascularized composite tissue allografts include skin, which frequently undergoes, in the early post-graft period, acute rejections. The diagnosis of acute rejection may be difficult as it can be mimicked by several dermatoses. We present a bilateral hand allograft recipient who developed, 16.5 years post-graft, cutaneous lesions raising suspicion about rejection. Physical examination and skin biopsy were diagnostic of scabies. This ectoparasitosis should be added in the list of dermatoses that can mimic allograft rejection in vascular composite allografts. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Small RNA-seq during acute maximal exercise reveal RNAs involved in vascular inflammation and cardiometabolic health: brief report.

    PubMed

    Shah, Ravi; Yeri, Ashish; Das, Avash; Courtright-Lim, Amanda; Ziegler, Olivia; Gervino, Ernest; Ocel, Jeffrey; Quintero-Pinzon, Pablo; Wooster, Luke; Bailey, Cole Shields; Tanriverdi, Kahraman; Beaulieu, Lea M; Freedman, Jane E; Ghiran, Ionita; Lewis, Gregory D; Van Keuren-Jensen, Kendall; Das, Saumya

    2017-12-01

    Exercise improves cardiometabolic and vascular function, although the mechanisms remain unclear. Our objective was to demonstrate the diversity of circulating extracellular RNA (ex-RNA) release during acute exercise in humans and its relevance to exercise-mediated benefits on vascular inflammation. We performed plasma small RNA sequencing in 26 individuals undergoing symptom-limited maximal treadmill exercise, with replication of our top candidate miRNA in a separate cohort of 59 individuals undergoing bicycle ergometry. We found changes in miRNAs and other ex-RNAs with exercise (e.g., Y RNAs and tRNAs) implicated in cardiovascular disease. In two independent cohorts of acute maximal exercise, we identified miR-181b-5p as a key ex-RNA increased in plasma after exercise, with validation in a separate cohort. In a mouse model of acute exercise, we found significant increases in miR-181b-5p expression in skeletal muscle after acute exercise in young (but not older) mice. Previous work revealed a strong role for miR-181b-5p in vascular inflammation in obesity, insulin resistance, sepsis, and cardiovascular disease. We conclude that circulating ex-RNAs were altered in plasma after acute exercise target pathways involved in inflammation, including miR-181b-5p. Further investigation into the role of known (e.g., miRNA) and novel (e.g., Y RNAs) RNAs is warranted to uncover new mechanisms of vascular inflammation on exercise-mediated benefits on health. NEW & NOTEWORTHY How exercise provides benefits to cardiometabolic health remains unclear. We performed RNA sequencing in plasma during exercise to identify the landscape of small noncoding circulating transcriptional changes. Our results suggest a link between inflammation and exercise, providing rich data on circulating noncoding RNAs for future studies by the scientific community. Copyright © 2017 the American Physiological Society.

  12. Maintenance of airway epithelium in acutely rejected orthotopic vascularized mouse lung transplants.

    PubMed

    Okazaki, Mikio; Gelman, Andrew E; Tietjens, Jeremy R; Ibricevic, Aida; Kornfeld, Christopher G; Huang, Howard J; Richardson, Steven B; Lai, Jiaming; Garbow, Joel R; Patterson, G Alexander; Krupnick, Alexander S; Brody, Steven L; Kreisel, Daniel

    2007-12-01

    Lung transplantation remains the only therapeutic option for many patients suffering from end-stage pulmonary disease. Long-term success after lung transplantation is severely limited by the development of bronchiolitis obliterans. The murine heterotopic tracheal transplantation model has been widely used for studies investigating pathogenesis of obliterative airway disease and immunosuppressive strategies to prevent its development. Despite its utility, this model employs proximal airway that lacks airflow and is not vascularized. We have developed a novel model of orthotopic vascularized lung transplantation in the mouse, which leads to severe vascular rejection in allogeneic strain combinations. Here we characterize differences in the fate of airway epithelial cells in nonimmunosuppressed heterotopic tracheal and vascularized lung allograft models over 28 days. Up-regulation of growth factors that are thought to be critical for the development of airway fibrosis and interstitial collagen deposition were similar in both models. However, while loss of airway epithelial cells occurred in the tracheal model, airway epithelium remained intact and fully differentiated in lung allografts, despite profound vascular rejection. Moreover, we demonstrate expression of the anti-apoptotic protein Bcl-2 in airway epithelial cells of acutely rejected lung allografts. These findings suggest that in addition to alloimmune responses, other stimuli may be required for the destruction of airway epithelial cells. Thus, the model of vascularized mouse lung transplantation may provide a new and more physiologic experimental tool to study the interaction between immune and nonimmune mechanisms affecting airway pathology in lung allografts.

  13. Stressful events and coping related to acute and sub-acute whiplash-associated disorders.

    PubMed

    Pettersson, Susanne; Bring, Annika; Åsenlöf, Pernilla

    2017-03-01

    Purpose To describe daily stressors affecting and coping strategies employed by individuals with whiplash-associated disorders (WAD) immediately to one month (acute) and three to four months (sub-acute) after injury events using a daily coping assessment. Levels of pain, anxiety, depressed mood and activity are also compared between phases. Method A descriptive prospective design with a content analysis approach was used. Participants completed daily coping assessments for one week during both acute and sub-acute phases. Main measure was whiplash-associated disorders-daily coping assessment (WAD-DCA). Results Nine participants used words describing recovery in the sub-acute phase; 31 described stressful events during both phases. Most frequently reported stressors were related to "symptoms", "emotions" and "occupations/studies". These were equally reported during both phases. Cognitive coping strategies were employed more often during the sub-acute phase (p = 0.008). The only behavioral strategy that increased in prevalence over time was the "relaxed" strategy (p = 0.001). Anxiety levels declined over time (p = 0.022). Conclusion The reported stressors were largely uniform across both acute and sub-acute phases; however, the use of cognitive coping strategies increased over time. The WAD-DCA captures individual stressors and coping strategies employed during a vulnerable phase of rehabilitation and can thus provide information that is useful to clinical practice. Implications for rehabilitation The WAD-DCA provides valuable information for clinical practice when employed during early phases of whiplash-associated disorder development. Reported stressors during the acute and sub-acute phases are essentially the same, whereas cognitive coping strategies grow in prevalence over time. Tailored treatments in early phases of whip-lash associated disorders may benefit from strategies aimed at matching patient-specific stressors with contextually adapted coping

  14. Relationship between risk factor control and vascular events in the SAMMPRIS trial.

    PubMed

    Turan, Tanya N; Nizam, Azhar; Lynn, Michael J; Egan, Brent M; Le, Ngoc-Anh; Lopes-Virella, Maria F; Hermayer, Kathie L; Harrell, Jamie; Derdeyn, Colin P; Fiorella, David; Janis, L Scott; Lane, Bethany; Montgomery, Jean; Chimowitz, Marc I

    2017-01-24

    The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study is the first stroke prevention trial to include protocol-driven intensive management of multiple risk factors. In this prespecified analysis, we aimed to investigate the relationship between risk factor control during follow-up and outcome of patients in the medical arm of SAMMPRIS. Data from SAMMPRIS participants in the medical arm (n = 227) were analyzed. Risk factors were recorded at baseline, 30 days, 4 months, and then every 4 months for a mean follow-up of 32 months. For each patient, values for all risk factor measures were averaged and dichotomized as in or out of target. Participants who were out of target for systolic blood pressure and physical activity, as well as those with higher mean low-density lipoprotein cholesterol and non-high-density lipoprotein, were more likely to have a recurrent vascular event (stroke, myocardial infarction, or vascular death) at 3 years compared to those who had good risk factor control. In the multivariable analysis, greater physical activity decreased the likelihood of a recurrent stroke, myocardial infarction, or vascular death (odds ratio 0.6, confidence interval 0.4-0.8). Raised blood pressure, cholesterol, and physical inactivity should be aggressively treated in patients with intracranial atherosclerosis to prevent future vascular events. Physical activity, which has not received attention in stroke prevention trials, was the strongest predictor of a good outcome in the medical arm in SAMMPRIS. NCT00576693. © 2016 American Academy of Neurology.

  15. Relationship between risk factor control and vascular events in the SAMMPRIS trial

    PubMed Central

    Nizam, Azhar; Lynn, Michael J.; Egan, Brent M.; Le, Ngoc-Anh; Lopes-Virella, Maria F.; Hermayer, Kathie L.; Harrell, Jamie; Derdeyn, Colin P.; Fiorella, David; Janis, L. Scott; Lane, Bethany; Montgomery, Jean; Chimowitz, Marc I.

    2017-01-01

    Objective: The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study is the first stroke prevention trial to include protocol-driven intensive management of multiple risk factors. In this prespecified analysis, we aimed to investigate the relationship between risk factor control during follow-up and outcome of patients in the medical arm of SAMMPRIS. Methods: Data from SAMMPRIS participants in the medical arm (n = 227) were analyzed. Risk factors were recorded at baseline, 30 days, 4 months, and then every 4 months for a mean follow-up of 32 months. For each patient, values for all risk factor measures were averaged and dichotomized as in or out of target. Results: Participants who were out of target for systolic blood pressure and physical activity, as well as those with higher mean low-density lipoprotein cholesterol and non–high-density lipoprotein, were more likely to have a recurrent vascular event (stroke, myocardial infarction, or vascular death) at 3 years compared to those who had good risk factor control. In the multivariable analysis, greater physical activity decreased the likelihood of a recurrent stroke, myocardial infarction, or vascular death (odds ratio 0.6, confidence interval 0.4–0.8). Conclusions: Raised blood pressure, cholesterol, and physical inactivity should be aggressively treated in patients with intracranial atherosclerosis to prevent future vascular events. Physical activity, which has not received attention in stroke prevention trials, was the strongest predictor of a good outcome in the medical arm in SAMMPRIS. ClinicalTrials.gov identifier: NCT00576693. PMID:28003500

  16. The effects of a multiflavonoid supplement on vascular and hemodynamic parameters following acute exercise.

    PubMed

    Kappus, Rebecca M; Curry, Chelsea D; McAnulty, Steve; Welsh, Janice; Morris, David; Nieman, David C; Soukup, Jeffrey; Collier, Scott R

    2011-01-01

    Antioxidants can decrease oxidative stress and combined with acute exercise they may lead to further decreases in blood pressure. The purpose of this study was to investigate the effects of 2 weeks of antioxidant supplementation on vascular distensibility and cardiovascular hemodynamics during postexercise hypotension. Twenty young subjects were randomized to placebo (n = 10) or antioxidant supplementation (n = 10) for two weeks. Antioxidant status, vascular distensibility, and hemodynamics were obtained before, immediately, and 30 minutes after an acute bout of aerobic exercise both before and after supplementation. Two weeks of antioxidant supplementation resulted in a greater systolic blood pressure (SBP) decrease during postexercise hypotension (PEH) and significant decreases in augmentation index versus placebo (12.5% versus 3.5%, resp.). Also ferric-reducing ability of plasma (FRAP) increased significantly (interaction P = 0.024) after supplementation. Supplementation showed an additive effect on PEH associated with increased FRAP values and decreases in systolic blood pressure and augmentation index.

  17. The Effects of a Multiflavonoid Supplement on Vascular and Hemodynamic Parameters following Acute Exercise

    PubMed Central

    Kappus, Rebecca M.; Curry, Chelsea D.; McAnulty, Steve; Welsh, Janice; Morris, David; Nieman, David C.; Soukup, Jeffrey; Collier, Scott R.

    2011-01-01

    Antioxidants can decrease oxidative stress and combined with acute exercise they may lead to further decreases in blood pressure. The purpose of this study was to investigate the effects of 2 weeks of antioxidant supplementation on vascular distensibility and cardiovascular hemodynamics during postexercise hypotension. Methods. Twenty young subjects were randomized to placebo (n = 10) or antioxidant supplementation (n = 10) for two weeks. Antioxidant status, vascular distensibility, and hemodynamics were obtained before, immediately, and 30 minutes after an acute bout of aerobic exercise both before and after supplementation. Results. Two weeks of antioxidant supplementation resulted in a greater systolic blood pressure (SBP) decrease during postexercise hypotension (PEH) and significant decreases in augmentation index versus placebo (12.5% versus 3.5%, resp.). Also ferric-reducing ability of plasma (FRAP) increased significantly (interaction P = 0.024) after supplementation. Conclusion. Supplementation showed an additive effect on PEH associated with increased FRAP values and decreases in systolic blood pressure and augmentation index. PMID:22191012

  18. Molecular mechanisms for vascular complications of targeted cancer therapies.

    PubMed

    Gopal, Srila; Miller, Kenneth B; Jaffe, Iris Z

    2016-10-01

    Molecularly targeted anti-cancer therapies have revolutionized cancer treatment by improving both quality of life and survival in cancer patients. However, many of these drugs are associated with cardiovascular toxicities that are sometimes dose-limiting. Moreover, the long-term cardiovascular consequences of these drugs, some of which are used chronically, are not yet known. Although the scope and mechanisms of the cardiac toxicities are better defined, the mechanisms for vascular toxicities are only beginning to be elucidated. This review summarizes what is known about the vascular adverse events associated with three classes of novel anti-cancer therapies: vascular endothelial growth factor (VEGF) inhibitors, breakpoint cluster-Abelson (BCR-ABL) kinase inhibitors used to treat chronic myelogenous leukaemia (CML) and immunomodulatory agents (IMiDs) used in myeloma therapeutics. Three of the best described vascular toxicities are reviewed including hypertension, increased risk of acute cardiovascular ischaemic events and arteriovenous thrombosis. The available data regarding the mechanism by which each therapy causes vascular complication are summarized. When data are limited, potential mechanisms are inferred from the known effects of inhibiting each target on vascular cell function and disease. Enhanced understanding of the molecular mechanisms of vascular side effects of targeted cancer therapy is necessary to effectively manage cancer patients and to design safer targeted cancer therapies for the future. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  19. Pulmonary vascular responses during acute and sustained respiratory alkalosis or acidosis in intact newborn piglets.

    PubMed

    Gordon, J B; Rehorst-Paea, L A; Hoffman, G M; Nelin, L D

    1999-12-01

    Acute alkalosis-induced pulmonary vasodilation and acidosis-induced pulmonary vasoconstriction have been well described, but responses were generally measured within 5-30 min of changing pH. In contrast, several in vitro studies have found that relatively brief periods of sustained alkalosis can enhance, and sustained acidosis can decrease, vascular reactivity. In this study of intact newborn piglets, effects of acute (20 min) and sustained (60-80 min) alkalosis or acidosis on baseline (35% O2) and hypoxic (12% O2) pulmonary vascular resistance (PVR) were compared with control piglets exposed only to eucapnia. Acute alkalosis decreased hypoxic PVR, but sustained alkalosis failed to attenuate either baseline PVR or the subsequent hypoxic response. Acute acidosis did not significantly increase hypoxic PVR, but sustained acidosis markedly increased both baseline PVR and the subsequent hypoxic response. Baseline PVR was similar in all piglets after resumption of eucapnic ventilation, but the final hypoxic response was greater in piglets previously exposed to alkalosis than in controls. Thus, hypoxic pulmonary vasoconstriction was not attenuated during sustained alkalosis, but was accentuated during sustained acidosis and after the resumption of eucapnia in alkalosis-treated piglets. Although extrapolation of data from normal piglets to infants and children with pulmonary hypertension must be done with caution, this study suggests that sustained alkalosis may be of limited efficacy in treating acute hypoxia-induced pulmonary hypertension and the risks of pulmonary hypertension must be considered when using ventilator strategies resulting in permissive hypercapnic acidosis.

  20. Optimising secondary prevention in the acute period following a TIA of ischaemic origin.

    PubMed

    Heron, Neil

    2016-01-01

    Transient ischaemic attacks (TIAs) are highly prevalent conditions, with at least 46 000 people per year in the UK having a TIA for the first time. TIAs are a warning that the patient is at risk of further vascular events and the 90-day risk of vascular events following a TIA, excluding events within the first week after diagnosis when the risk is highest, can be as high as 18%. Immediate assessment of patients with TIA, either at accident and emergency, general practice and/or TIA clinics, is therefore required to address secondary prevention and prevent further vascular events. This article addresses the need for optimising secondary prevention in the acute period following a TIA of ischaemic origin to reduce the risk of further vascular events as per recent Cochrane review advice and presents a novel project, Stroke Prevention Rehabilitation Intervention Trial of Exercise (SPRITE), to do this. One novel way to tackle vascular risk factors and promote secondary prevention in patients with TIA could be to adapt a cardiac rehabilitation programme for these patients. SPRITE, a feasibility and pilot study (ClinicalTrials.gov Identifier: NCT02712385) funded by the National Institute for Health Research, is attempting to adapt a home-based cardiac rehabilitation programme, 'The Healthy Brain Rehabilitation Manual', for use in the acute period following a TIA. The use of cardiac rehabilitation programmes post-TIA requires further research, particularly within the primary care setting.

  1. Clinical correlates of acute pulmonary events in children and adolescents with sickle cell disease*

    PubMed Central

    Paul, Rabindra; Minniti, Caterina P.; Nouraie, Mehdi; Luchtman-Jones, Lori; Campbell, Andrew; Rana, Sohail; Onyekwere, Onyinye; Darbari, Deepika S.; Ajayi, Olaid; Arteta, Manuel; Ensing, Gregory; Sable, Craig; Dham, Niti; Kato, Gregory J.; Gladwin, Mark T.; Castro, Oswaldo L.; Gordeuk, Victor R.

    2013-01-01

    Objectives We aimed to identify risk factors for acute pulmonary events in children and adolescents in the Pulmonary Hypertension and the Hypoxic Response in SCD (PUSH) study. Methods Patients with hemoglobin SS (n=376) and other sickle cell genotypes (n=127) aged 3-20 years were studied at four centers in a cross-sectional manner. A sub-group (n=293) was followed for a median of 21 months (range 9-35). Results A patient-reported history of one or more acute pulmonary events, either acute chest syndrome (ACS) or pneumonia, was obtained in 195 hemoglobin SS patients (52%) and 51 patients with other genotypes (40%). By logistic regression, history of acute pulmonary events was independently associated with patient-reported history of asthma (p<0.0001), older age (p=0.001), >3 severe pain episodes in the preceding 12 months (p=0.002), higher tricuspid regurgitation velocity (TRV) (p=0.028), and higher white blood cell (WBC) count (p=0.043) among hemoglobin SS patients. History of acute pulmonary events was associated with >3 severe pain episodes (p=0.009) among patients with other genotypes. During follow-up, 43 patients (15%) had at least one new ACS episode including 11 without a baseline history of acute pulmonary events. History of acute pulmonary events (odds ratio 5.4; p<0.0001) and younger age (odds ratio 0.9; p=0.010) were independently associated with developing a new episode during follow-up. Conclusions Asthma history, frequent pain and higher values for TRV and WBC count were independently associated with history of acute pulmonary events in hemoglobin SS patients and frequent pain was associated in those with other genotypes. Measures to reduce pain episodes and control asthma may help to decrease the incidence of acute pulmonary events in SCD. PMID:23560516

  2. Design and rationale of the AngioSeal versus the Radial approach In acute coronary SyndromE (ARISE) trial: a randomized comparison of a vascular closure device versus the radial approach to prevent vascular access site complications in non-ST-segment elevation acute coronary syndrome patients.

    PubMed

    de Andrade, Pedro Beraldo; E Mattos, Luiz Alberto Piva; Tebet, Marden André; Rinaldi, Fábio Salerno; Esteves, Vinícius Cardozo; Nogueira, Ederlon Ferreira; França, João Ítalo Dias; de Andrade, Mônica Vieira Athanazio; Barbosa, Robson Alves; Labrunie, André; Abizaid, Alexandre Antônio Cunha; Sousa, Amanda Guerra de Moraes Rego

    2013-12-18

    Arterial access is a major site of bleeding complications after invasive coronary procedures. Among strategies to decrease vascular complications, the radial approach is an established one. Vascular closure devices provide more comfort to patients and decrease hemostasis and need for bed rest. However, the inconsistency of data proving their safety limits their routine adoption as a strategy to prevent vascular complications, requiring evidence through adequately designed randomized trials. The aim of this study is to compare the radial versus femoral approach using a vascular closure device for the incidence of arterial puncture site vascular complications among non-ST-segment elevation acute coronary syndrome patients submitted to an early invasive strategy. ARISE is a national, multicenter, non-inferiority randomized clinical trial. Two hundred patients with non-ST-segment elevation acute coronary syndrome will be randomized to either radial or femoral access using a vascular closure device. The primary outcome is the occurrence of vascular complications at an arterial puncture site 30 days after the procedure, including major bleeding, retroperitoneal hematoma, compartment syndrome, hematoma ≥ 5 cm, pseudoaneurysm, arterio-venous fistula, infection, limb ischemia, arterial occlusion, adjacent nerve injury or the need for vascular surgical repair. Enrollment was initiated in September 2012, and until October 2013 91 patients were included. The inclusion phase is expected to last until the second half of 2014. The ARISE trial will help define the role of a vascular closure device as a bleeding avoidance strategy in patients with NSTEACS. ClinicalTrials.gov identifier: NCT01653587.

  3. Acute effect of sidestream cigarette smoke extract on vascular endothelial function.

    PubMed

    Argacha, J F; Fontaine, D; Adamopoulos, D; Ajose, A; van de Borne, P; Fontaine, J; Berkenboom, G

    2008-09-01

    Acute exposure to passive smoking adversely affects vascular function by promoting oxidative stress and endothelial dysfunction. However, it is not known whether tobacco sidestream (SS) smoke has a greater deleterious effect on the endothelium than non-tobacco SS smoke and whether these effects are related to nicotinic endothelial stimulation. To test these hypotheses, endothelial-dependent relaxation and superoxide anion production were assessed in isolated rat aortas incubated with tobacco SS smoke, non-tobacco SS smoke, or pure nicotine. Tobacco SS smoke decreased the maximal relaxation to acetylcholine (Ach) from 79 +/- 6% to 57 +/- 7.3% (% inhibition of phenylephrine-induced plateau, P < 0.001) and increased superoxide anion production from 31 +/- 9.7 to 116 +/- 24 count/10 sec/mg (P < 0.01, lucigenin-enhanced chemiluminescence technique). The non-tobacco SS smoke extract had no significant effect on the response to Ach but increased superoxide anion production in the aortic wall to 133 +/- 2 count/10 sec/mg (P < 0.001). Furthermore, concentration-response curves to Ach and superoxide production remained unaltered with nicotine (0.001, 0.01, or 0.1 mM). In conclusion, despite similar increases in vascular wall superoxide production with tobacco and non-tobacco SS smoke, only the tobacco SS smoke extracts affected endothelium-dependent vasorelaxation. Nicotine alone does not reproduce the effects seen with tobacco SS smoke, suggesting that the acute endothelial toxicity of passive smoking cannot simply be ascribed to a nicotine-dependent mechanism.

  4. Worrying About Terrorism and Other Acute Environmental Health Hazard Events

    PubMed Central

    Babcock-Dunning, Lauren

    2012-01-01

    Objectives. To better understand why some people worry more about terrorism compared with others, we measured how much US residents worried about a terrorist event in their area and examined the association of their fears with their concerns about acute and chronic hazards and other correlates. Methods. In 2008 (n = 600) and 2010 (n = 651), we performed a random-digit dialing national landline telephone survey. We asked about worries about terrorism and 5 other environmental health hazard issues. We also collected demographic and socioeconomic data. Results. Only 15% worried “a great deal” about a terrorist event in their area and 18% to 33% were greatly concerned about other environmental issues. Fear about acute hazard events was a stronger predictor of a great deal of concern about terrorism than were age, race/ethnicity, gender, educational achievement, and other correlates. Conclusions. Those who worried most about acute environmental health hazard events were most likely to worry about terrorism. Also, those who were older, poorer, Blacks, or Latinos, or who lived in populous urban areas felt they were most vulnerable to terrorist attacks. We recommend methods to involve US citizens as part of disaster planning. PMID:22397346

  5. Worrying about terrorism and other acute environmental health hazard events.

    PubMed

    Greenberg, Michael; Babcock-Dunning, Lauren

    2012-04-01

    To better understand why some people worry more about terrorism compared with others, we measured how much US residents worried about a terrorist event in their area and examined the association of their fears with their concerns about acute and chronic hazards and other correlates. In 2008 (n = 600) and 2010 (n = 651), we performed a random-digit dialing national landline telephone survey. We asked about worries about terrorism and 5 other environmental health hazard issues. We also collected demographic and socioeconomic data. Only 15% worried "a great deal" about a terrorist event in their area and 18% to 33% were greatly concerned about other environmental issues. Fear about acute hazard events was a stronger predictor of a great deal of concern about terrorism than were age, race/ethnicity, gender, educational achievement, and other correlates. Those who worried most about acute environmental health hazard events were most likely to worry about terrorism. Also, those who were older, poorer, Blacks, or Latinos, or who lived in populous urban areas felt they were most vulnerable to terrorist attacks. We recommend methods to involve US citizens as part of disaster planning.

  6. Aldosterone, mortality, and acute ischaemic events in coronary artery disease patients outside the setting of acute myocardial infarction or heart failure.

    PubMed

    Ivanes, Fabrice; Susen, Sophie; Mouquet, Frédéric; Pigny, Pascal; Cuilleret, François; Sautière, Karine; Collet, Jean-Philippe; Beygui, Farzin; Hennache, Bernadette; Ennezat, Pierre Vladimir; Juthier, Françis; Richard, Florence; Dallongeville, Jean; Hillaert, Marieke A; Doevendans, Pieter A; Jude, Brigitte; Bertrand, Michel; Montalescot, Gilles; Van Belle, Eric

    2012-01-01

    Recent studies have demonstrated that aldosterone levels measured in patients with heart failure or acute myocardial infarction (MI) are associated with long-term mortality, but the association with aldosterone levels in patients with coronary artery disease (CAD) outside these specific settings remains unknown. In addition, no clear mechanism has been elucidated to explain these observations. The present study was designed to evaluate the relationship between the level of aldosterone and the risk of death and acute ischaemic events in CAD patients with a preserved left ventricular (LV) function and no acute MI. In 799 consecutive CAD patients referred for elective coronary angioplasty measurements were obtained before the procedure for: aldosterone (median = 25 pg/mL), brain natriuretic peptide (BNP) (median = 35 pg/mL), hsC-reactive protein (median = 4.17 mg/L), and left ventricular ejection fraction (mean = 58%). Patients with acute MI or coronary syndrome (ACS) who required urgent revascularization were not included in the study. The primary endpoint, cardiovascular death, occurred in 41 patients during a median follow-up period of 14.9 months. Secondary endpoints-total mortality, acute ischaemic events (acute MI or ischaemic stroke), and the composite of death and acute ischaemic events-were observed in 52, 54, and 94 patients, respectively. Plasma aldosterone was found to be related to BMI, hypertension and NYHA class, and inversely related to age, creatinine clearance, and use of beta-blockers. Multivariate Cox model analysis demonstrated that aldosterone was independently associated with cardiovascular mortality (P = 0.001), total mortality (P = 0.001), acute ischaemic events (P = 0.01), and the composite of death and acute ischaemic events (P = 0.004). Reclassification analysis, using integrated discrimination improvement (IDI) and net reclassification improvement (NRI), demonstrated incremental predictive value of aldosterone (P < 0.0001). Our results

  7. Local Tacrolimus (FK506) Delivery for Prevention of Acute Rejection in the Nonhuman Primate Delayed Mixed Chimerism Vascularized Composite Allograft Tolerance Induction Protocol

    DTIC Science & Technology

    2016-10-01

    Chimerism Vascularized Composite Allograft Tolerance Induction Protocol PRINCIPAL INVESTIGATORS: Dr. Curtis L. Cetrulo CONTRACTING ORGANIZATION...Tacrolimus (FK506) Delivery for Prevention of Acute Rejection in the Nonhuman Primate Delayed Mixed Chimerism Vascularized Composite Allograft Tolerance...tacrolimus, FK506, vascularized composite allografts , immune rejection, preclinical, transplant, nonhuman primate model, degradable polymer, tyrosine

  8. Modeling Acute Health Effects of Astronauts from Exposure to Large Solar Particle Events

    NASA Technical Reports Server (NTRS)

    Hu, Shaowen; Kim, Myung-Hee Y.; Cucinotta, Francis A.

    2011-01-01

    In space exploration outside the Earth s geomagnetic field, radiation exposure from solar particle events (SPE) presents a health concern for astronauts, that could impair their performance and result in possible failure of the mission. Acute risks are of special concern during extra-vehicular activities because of the rapid onset of SPE. However, most SPEs will not lead to acute risks but can lead to mission disruption if accurate projection methods are not available. Acute Radiation Sickness (ARS) is a group of clinical syndromes developing acutely (within several seconds to 3 days) after high dose whole-body or significant partial-body ionizing radiation exposures. The manifestation of these syndromes reflects the disturbance of physiological processes of various cellular groups damaged by radiation. Hematopoietic cells, skin, epithelium, intestine, and vascular endothelium are among the most sensitive tissues of human body to ionizing radiation. Most ARS symptoms are directly related to these tissues and other systems (nervous, endocrine, and cardiovascular, etc.) with coupled regulations. Here we report the progress in bio-mathematical models to describe the dose and time-dependent early human responses to ionizing radiation. The responses include lymphocyte depression, granulocyte modulation, fatigue and weakness syndrome, and upper gastrointestinal distress. The modest dose and dose-rates of SPEs are predicted to lead to large sparing of ARS, however detailed experimental data on a range of proton dose-rates for organ doses from 0.5 to 2 Gy is needed to validate the models. We also report on the ARRBOD code that integrates the BRYNTRN and SUMDOSE codes, which are used to estimate the SPE organ doses for astronauts under various space travel scenarios, with our models of ARS. The more recent effort is to provide easy web access to space radiation risk assessment using the ARRBOD code.

  9. Predictive value of reactive hyperemia for cardiovascular events in patients with peripheral arterial disease undergoing vascular surgery.

    PubMed

    Huang, Alex L; Silver, Annemarie E; Shvenke, Elena; Schopfer, David W; Jahangir, Eiman; Titas, Megan A; Shpilman, Alex; Menzoian, James O; Watkins, Michael T; Raffetto, Joseph D; Gibbons, Gary; Woodson, Jonathan; Shaw, Palma M; Dhadly, Mandeep; Eberhardt, Robert T; Keaney, John F; Gokce, Noyan; Vita, Joseph A

    2007-10-01

    Reactive hyperemia is the compensatory increase in blood flow that occurs after a period of tissue ischemia, and this response is blunted in patients with cardiovascular risk factors. The predictive value of reactive hyperemia for cardiovascular events in patients with atherosclerosis and the relative importance of reactive hyperemia compared with other measures of vascular function have not been previously studied. We prospectively measured reactive hyperemia and brachial artery flow-mediated dilation by ultrasound in 267 patients with peripheral arterial disease referred for vascular surgery (age 66+/-11 years, 26% female). Median follow-up was 309 days (range 1 to 730 days). Fifty patients (19%) had an event, including cardiac death (15), myocardial infarction (18), unstable angina (8), congestive heart failure (6), and nonhemorrhagic stroke (3). Patients with an event were older and had lower hyperemic flow velocity (75+/-39 versus 95+/-50 cm/s, P=0.009). Patients with an event also had lower flow-mediated dilation (4.5+/-3.0 versus 6.9+/-4.6%, P<0.001), and when these 2 measures of vascular function were included in the same Cox proportional hazards model, lower hyperemic flow (OR 2.7, 95% CI 1.2 to 5.9, P=0.018) and lower flow-mediated dilation (OR 4.2, 95% CI: 1.8 to 9.8, P=0.001) both predicted cardiovascular events while adjusting for other risk factors. Thus, lower reactive hyperemia is associated with increased cardiovascular risk in patients with peripheral arterial disease. Furthermore, flow-mediated dilation and reactive hyperemia incrementally relate to cardiovascular risk, although impaired flow-mediated dilation was the stronger predictor in this population. These findings further support the clinical relevance of vascular function measured in the microvasculature and conduit arteries in the upper extremity.

  10. Predictive Value of Reactive Hyperemia for Cardiovascular Events in Patients With Peripheral Arterial Disease Undergoing Vascular Surgery

    PubMed Central

    Huang, Alex L.; Silver, Annemarie E.; Shvenke, Elena; Schopfer, David W.; Jahangir, Eiman; Titas, Megan A.; Shpilman, Alex; Menzoian, James O.; Watkins, Michael T.; Raffetto, Joseph D.; Gibbons, Gary; Woodson, Jonathan; Shaw, Palma M.; Dhadly, Mandeep; Eberhardt, Robert T.; Keaney, John F.; Gokce, Noyan; Vita, Joseph A.

    2008-01-01

    Objective Reactive hyperemia is the compensatory increase in blood flow that occurs after a period of tissue ischemia, and this response is blunted in patients with cardiovascular risk factors. The predictive value of reactive hyperemia for cardiovascular events in patients with atherosclerosis and the relative importance of reactive hyperemia compared with other measures of vascular function have not been previously studied. Methods and Results We prospectively measured reactive hyperemia and brachial artery flow-mediated dilation by ultrasound in 267 patients with peripheral arterial disease referred for vascular surgery (age 66±11 years, 26% female). Median follow-up was 309 days (range 1 to 730 days). Fifty patients (19%) had an event, including cardiac death (15), myocardial infarction (18), unstable angina (8), congestive heart failure (6), and nonhemorrhagic stroke (3). Patients with an event were older and had lower hyperemic flow velocity (75±39 versus 95±50 cm/s, P=0.009). Patients with an event also had lower flow-mediated dilation (4.5±3.0 versus 6.9±4.6%, P<0.001), and when these 2 measures of vascular function were included in the same Cox proportional hazards model, lower hyperemic flow (OR 2.7, 95% CI 1.2 to 5.9, P=0.018) and lower flow-mediated dilation (OR 4.2, 95% CI: 1.8 to 9.8, P=0.001) both predicted cardiovascular events while adjusting for other risk factors. Conclusions Thus, lower reactive hyperemia is associated with increased cardiovascular risk in patients with peripheral arterial disease. Furthermore, flow-mediated dilation and reactive hyperemia incrementally relate to cardiovascular risk, although impaired flow-mediated dilation was the stronger predictor in this population. These findings further support the clinical relevance of vascular function measured in the microvasculature and conduit arteries in the upper extremity. PMID:17717291

  11. Catastrophic antiphospholipid antibody syndrome presenting as acute vascular occlusion in a young female patient.

    PubMed

    Alonso, Joaquín Valle; Del Pozo, Francisco Javier Fonseca; Álvarez, Manuel Vaquero; Pedraza, Jorge; Aguayo, Miguel Angel; Sanchez, Almudena

    Acquired thrombotic and thromboembolic disorders may be presented initially with symptoms and signs of acute ischaemia or organ dysfunction that will lead many of these patients to seek care in the emergency department. We report a case of a 19-year-old female patient who developed catastrophic antiphospholipid syndrome (CAPS syndrome or Asherson syndrome) 6 weeks post stillbirth with an initial presentation of acute vascular occlusion. The patient was immediately operated and anticoagulated with significant improvement. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  12. Acute hemolytic vascular inflammatory processes are prevented by nitric oxide replacement or a single dose of hydroxyurea.

    PubMed

    Almeida, Camila Bononi; Souza, Lucas Eduardo Botelho; Leonardo, Flavia Costa; Costa, Fabio Trindade Maranhão; Werneck, Claudio C; Covas, Dimas Tadeu; Costa, Fernando Ferreira; Conran, Nicola

    2015-08-06

    Hemolysis and consequent release of cell-free hemoglobin (CFHb) impair vascular nitric oxide (NO) bioavailability and cause oxidative and inflammatory processes. Hydroxyurea (HU), a common therapy for sickle cell disease (SCD), induces fetal Hb production and can act as an NO donor. We evaluated the acute inflammatory effects of intravenous water-induced hemolysis in C57BL/6 mice and determined the abilities of an NO donor, diethylamine NONOate (DEANO), and a single dose of HU to modulate this inflammation. Intravenous water induced acute hemolysis in C57BL/6 mice, attaining plasma Hb levels comparable to those observed in chimeric SCD mice. This hemolysis resulted in significant and rapid systemic inflammation and vascular leukocyte recruitment within 15 minutes, accompanied by NO metabolite generation. Administration of another potent NO scavenger (2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) to C57BL/6 mice induced similar alterations in leukocyte recruitment, whereas hemin-induced inflammation occurred over a longer time frame. Importantly, the acute inflammatory effects of water-induced hemolysis were abolished by the simultaneous administration of DEANO or HU, without altering CFHb, in an NO pathway-mediated manner. In vitro, HU partially reversed the Hb-mediated induction of endothelial proinflammatory cytokine secretion and adhesion molecule expression. In summary, pathophysiological levels of hemolysis trigger an immediate inflammatory response, possibly mediated by vascular NO consumption. HU presents beneficial anti-inflammatory effects by inhibiting rapid-onset hemolytic inflammation via an NO-dependent mechanism, independently of fetal Hb elevation. Data provide novel insights into mechanisms of hemolytic inflammation and further support perspectives for the use of HU as an acute treatment for SCD and other hemolytic disorders. © 2015 by The American Society of Hematology.

  13. Benign vascular proliferation in a lymph node following acute toxoplasmosis. A differential diagnosis from Kaposi's sarcoma.

    PubMed

    Rousselet, M C; Saint-André, J P; Beaufils, J M; Diebold, J

    1988-12-01

    We describe an unusual intranodal vascular proliferation following acute toxoplasmosis in a man. This proliferation is distinct from other benign vasoformative nodal lesions. It could be interpreted as a reactive healing process that might be misdiagnosed as nodal Kaposi's sarcoma. Some criteria to avoid such misdiagnosis are presented.

  14. Disaster metrics: quantification of acute medical disasters in trauma-related multiple casualty events through modeling of the Acute Medical Severity Index.

    PubMed

    Bayram, Jamil D; Zuabi, Shawki

    2012-04-01

    The interaction between the acute medical consequences of a Multiple Casualty Event (MCE) and the total medical capacity of the community affected determines if the event amounts to an acute medical disaster. There is a need for a comprehensive quantitative model in MCE that would account for both prehospital and hospital-based acute medical systems, leading to the quantification of acute medical disasters. Such a proposed model needs to be flexible enough in its application to accommodate a priori estimation as part of the decision-making process and a posteriori evaluation for total quality management purposes. The concept proposed by de Boer et al in 1989, along with the disaster metrics quantitative models proposed by Bayram et al on hospital surge capacity and prehospital medical response, were used as theoretical frameworks for a new comprehensive model, taking into account both prehospital and hospital systems, in order to quantify acute medical disasters. A quantitative model called the Acute Medical Severity Index (AMSI) was developed. AMSI is the proportion of the Acute Medical Burden (AMB) resulting from the event, compared to the Total Medical Capacity (TMC) of the community affected; AMSI = AMB/TMC. In this model, AMB is defined as the sum of critical (T1) and moderate (T2) casualties caused by the event, while TMC is a function of the Total Hospital Capacity (THC) and the medical rescue factor (R) accounting for the hospital-based and prehospital medical systems, respectively. Qualitatively, the authors define acute medical disaster as "a state after any type of Multiple Casualty Event where the Acute Medical Burden (AMB) exceeds the Total Medical Capacity (TMC) of the community affected." Quantitatively, an acute medical disaster has an AMSI value of more than one (AMB / TMC > 1). An acute medical incident has an AMSI value of less than one, without the need for medical surge. An acute medical emergency has an AMSI value of less than one with

  15. Impact of Aura and Status Migrainosus on Readmissions for Vascular Events After Migraine Admission.

    PubMed

    Velickovic Ostojic, Lili; Liang, John W; Sheikh, Huma U; Dhamoon, Mandip S

    2018-06-22

    -To estimate readmission rates for acute ischemic stroke (AIS), transient ischemic attack (TIA), subarachnoid hemorrhage, and intracerebral hemorrhage after an index admission for migraine, using nationally representative data. -The Nationwide Readmissions Database was designed to analyze readmissions for all payers and uninsured, with data on >14 million US admissions in 2013. We used International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify index migraine admissions with and without aura or status migrainosus, and readmissions for cerebrovascular events. Cox proportional hazards regression was performed for each outcome with aura and status migrainosus as main predictors, adjusting for age and vascular risk factors. -Out of 12,448 index admissions for migraine, 9972 (80.1%) were women, mean age was 45.5 ± 14.8 years, aura was present in 3038 (24.41%), and status migrainosus in 1798 (14.44%). The 30-day readmission rate (per 100,000 index admissions) was 154 for ischemic stroke, 86 for TIA, 42 for subarachnoid hemorrhage, and 17 for intracranial hemorrhage. In unadjusted models, aura was significantly associated with TIA (hazard ratio 2.43, 95% CI 1.39-4.24), but not AIS (1.26, 0.73-2.18), intracranial hemorrhage (1.86, 0.45-7.79) or subarachnoid hemorrhage (1.85, 0.44-7.75). When adjusting for age and vascular risk factors, aura remained significantly associated with TIA (2.13, 1.22-3.74). Status, in adjusted models, was significantly associated with subarachnoid hemorrhage readmission (4.83, 1.09-21.42). -In this large, nationally representative retrospective cohort study, migraine admission with aura was independently associated with TIA readmission, and status migrainosus was independently associated with subarachnoid hemorrhage. Further research would clarify the role of misdiagnosis and causal relationships underlying these strong associations. © 2018 American Headache Society.

  16. Vascular Physiology according to Clinical Scenario in Patients with Acute Heart Failure: Evaluation using the Cardio-Ankle Vascular Index.

    PubMed

    Goto, Toshihiko; Wakami, Kazuaki; Mori, Kento; Kikuchi, Shohei; Fukuta, Hidekatsu; Ohte, Nobuyuki

    2016-09-01

    Increased aortic stiffness may be an important cause of acute heart failure (AHF). Clinical scenario (CS), which classifies the pathophysiology of AHF based on the initial systolic blood pressure (sBP), was proposed to provide the most appropriate therapy for AHF patients. In CS, elevated aortic stiffness, vascular failure, has been considered as a feature of patients categorized as CS1 (sBP > 140 mmHg at initial presentation). However, whether elevated aortic stiffness, vascular failure, is present in such patients has not been fully elucidated. Therefore, we assessed aortic stiffness in AHF patients using the cardio-ankle vascular index (CAVI), which is considered to be independent of instantaneous blood pressure. Sixty-four consecutive AHF patients (mean age, 70.6 ± 12.8 years; 39 men) were classified with CS, based on their initial sBP: CS1: sBP > 140 mmHg (n = 29); CS2: sBP 100-140 mmHg (n = 22); and CS3: sBP < 100 mmHg (n = 13). There were significant group differences in CAVI (CS1 vs. CS2 vs. CS3: 9.7 ± 1.4 vs. 8.4 ± 1.7 vs. 8.3 ± 1.7, p = 0.006, analysis of variance). CAVI was significantly higher in CS1 than in CS2 (p = 0.02) and CS3 (p = 0.04). CAVI did not significantly correlate with sBP at the time of measurement of CAVI (r = 0.24 and p = 0.06). Aortic stiffness assessed using blood pressure-independent methodology apparently increased in CS1 AHF patients. We conclude that vascular failure is a feature of CS1 AHF initiation.

  17. Stressful life events and acute kidney injury in intensive and semi-intensive care unities.

    PubMed

    Diniz, Denise Para; Marques, Daniella Aparecida; Blay, Sérgio Luis; Schor, Nestor

    2012-03-01

    Several studies point out that pathophysiological changes related to stress may influence renal function and are associated with disease onset and evolution. However, we have not found any studies about the influence of stress on renal function and acute kidney injury. To evaluate the association between stressful life events and acute kidney injury diagnosis, specifying the most stressful classes of events for these patients in the past 12 months. Case-control study. The study was carried out at Hospital São Paulo, in Universidade Federal de São Paulo and at Hospital dos Servidores do Estado de São Paulo, in Brazil. Patients with acute kidney injury and no chronic disease, admitted to the intensive or semi-intensive care units were included. Controls included patients in the same intensive care units with other acute diseases, except for the acute kidney injury, and also with no chronic disease. Out of the 579 patients initially identified, 475 answered to the Social Readjustment Rating Scale (SRRS) questionnaire and 398 were paired by age and gender (199 cases and 199 controls). The rate of stressful life events was statistically similar between cases and controls. The logistic regression analysis to detect associated effects of the independent variables to the stressful events showed that: increasing age and economic classes A and B in one of the hospitals (Hospital São Paulo - UNIFESP) increased the chance of a stressful life event (SLE). This study did not show association between the Acute Kidney Injury Group with a higher frequency of stressful life events, but that old age, higher income, and type of clinical center were associated.

  18. Anticoagulant therapy and outcomes in patients with prior or acute heart failure and acute coronary syndromes: Insights from the APixaban for PRevention of Acute ISchemic Events 2 trial.

    PubMed

    Cornel, Jan H; Lopes, Renato D; James, Stefan; Stevens, Susanna R; Neely, Megan L; Liaw, Danny; Miller, Julie; Mohan, Puneet; Amerena, John; Raev, Dimitar; Huo, Yong; Urina-Triana, Miguel; Gallegos Cazorla, Alex; Vinereanu, Dragos; Fridrich, Viliam; Harrington, Robert A; Wallentin, Lars; Alexander, John H

    2015-04-01

    Clinical outcomes and the effects of oral anticoagulants among patients with acute coronary syndrome (ACS) and either a history of or acute heart failure (HF) are largely unknown. We aimed to assess the relationship between prior HF or acute HF complicating an index ACS event and subsequent clinical outcomes and the efficacy and safety of apixaban compared with placebo in these populations. High-risk patients were randomly assigned post-ACS to apixaban 5.0 mg or placebo twice daily. Median follow-up was 8 (4-12) months. The primary outcome was cardiovascular death, myocardial infarction, or stroke. The main safety outcome was thrombolysis in myocardial infarction major bleeding. Heart failure was reported in 2,995 patients (41%), either as prior HF (2,076 [28%]) or acute HF (2,028 [27%]). Patients with HF had a very high baseline risk and were more often managed medically. Heart failure was associated with a higher rate of the primary outcome (prior HF: adjusted hazard ratio [HR] 1.73, 95% CI 1.42-2.10, P < .0001, acute HF: adjusted HR 1.65, 95% CI 1.35-2.01, P < .0001) and cardiovascular death (prior HF: HR 2.54, 95% CI 1.82-3.54, acute HF: adjusted HR 2.52, 95% CI 1.82-3.50). Patients with acute HF also had significantly higher rates of thrombolysis in myocardial infarction major bleeding (prior HF: adjusted HR 1.22, 95% CI 0.65-2.27, P = .54, acute HF: adjusted HR 1.78, 95% CI 1.03-3.08, P = .04). There was no statistical evidence of a differential effect of apixaban on clinical events or bleeding in patients with or without prior HF; however, among patients with acute HF, there were numerically fewer events with apixaban than placebo (14.8 vs 19.3, HR 0.76, 95% CI 0.57-1.01, interaction P = .13), a trend that was not seen in patients with prior HF or no HF. In high-risk patients post-ACS, both prior and acute HFs are associated with an increased risk of subsequent clinical events. Apixaban did not significantly reduce clinical events and increased bleeding in

  19. Mast Cell Dependent Vascular Changes Associated with an Acute Response to Cold Immersion in Primary Contact Urticaria

    PubMed Central

    Meyer, Joseph; Gorbach, Alexander M.; Liu, Wei-Min; Medic, Nevenka; Young, Michael; Nelson, Celeste; Arceo, Sarah; Desai, Avanti; Metcalfe, Dean D.; Komarow, Hirsh D.

    2013-01-01

    Background While a number of the consequences of mast cell degranulation within tissues have been documented including tissue-specific changes such as bronchospasm and the subsequent cellular infiltrate, there is little known about the immediate effects of mast cell degranulation on the associated vasculature, critical to understanding the evolution of mast cell dependent inflammation. Objective To characterize the microcirculatory events that follow mast cell degranulation. Methodology/Principal Findings Perturbations in dermal blood flow, temperature and skin color were analyzed using laser-speckle contrast imaging, infrared and polarized-light colorimetry following cold-hand immersion (CHI) challenge in patients with cold-induced urticaria compared to the response in healthy controls. Evidence for mast cell degranulation was established by documentation of serum histamine levels and the localized release of tryptase in post-challenge urticarial biopsies. Laser-speckle contrast imaging quantified the attenuated response to cold challenge in patients on cetirizine. We found that the histamine-associated vascular response accompanying mast cell degranulation is rapid and extensive. At the tissue level, it is characterized by a uniform pattern of increased blood flow, thermal warming, vasodilation, and recruitment of collateral circulation. These vascular responses are modified by the administration of an antihistamine. Conclusions/Significance Monitoring the hemodynamic responses within tissues that are associated with mast cell degranulation provides additional insight into the evolution of the acute inflammatory response and offers a unique approach to assess the effectiveness of treatment intervention. PMID:23451084

  20. Increased Risk of Vascular Events in Emergency Room Patients Discharged Home with Diagnosis of Dizziness or Vertigo: A 3-Year Follow-Up Study

    PubMed Central

    Lee, Ching-Chih; Ho, Hsu-Chueh; Su, Yu-Chieh; Chiu, Brian C-H; Su, Yung-Cheng; Lee, Yi-Da; Chou, Pesus

    2012-01-01

    Background Dizziness and vertigo symptoms are commonly seen in emergency room (ER). However, these patients are often discharged without a definite diagnosis. Conflicting data regarding the vascular event risk among the dizziness or vertigo patients have been reported. This study aims to determine the risk of developing stroke or cardiovascular events in ER patients discharged home with a diagnosis of dizziness or vertigo. Methodology A total of 25,757 subjects with at least one ER visit in 2004 were identified. Of those, 1,118 patients were discharged home with a diagnosis of vertigo or dizziness. A Cox proportional hazard model was performed to compare the three-year vascular event-free survival rates between the dizziness/vertigo patients and those without dizziness/vertigo after adjusting for confounding and risk factors. Results We identified 52 (4.7%) vascular events in patients with dizziness/vertigo and 454 (1.8%) vascular events in patients without dizziness/vertigo. ER patients discharged home with a diagnosis of vertigo or dizziness had 2-fold (95% confidence interval [CI], 1.35–2.96; p<0.001) higher risk of stroke or cardiovascular events after adjusting for patient characteristics, co-morbidities, urbanization level of residence, individual socio-economic status, and initially taking medications after the onset of dizziness or vertigo during the first year. Conclusions ER patients discharged home with a diagnosis of dizziness or vertigo were at a increased risk of developing subsequent vascular events than those without dizziness/vertigo after the onset of dizziness or vertigo. Further studies are warranted for developing better diagnostic and follow-up strategies in increased risk patients. PMID:22558272

  1. Outcomes of Peripheral Vascular Interventions in Select Patients With Lower Extremity Acute Limb Ischemia.

    PubMed

    Inagaki, Elica; Farber, Alik; Kalish, Jeffrey A; Eslami, Mohammad H; Siracuse, Jeffrey J; Eberhardt, Robert T; Rybin, Denis V; Doros, Gheorghe; Hamburg, Naomi M

    2018-04-12

    Contemporary data on patients presenting with acute limb ischemia (ALI), who are selected for treatment with endovascular peripheral vascular interventions (PVI), are limited. Our study examined outcomes following endovascular PVI in patients with ALI by comparing with patients treated for chronic critical limb ischemia using a regional quality improvement registry. Of the 11 035 patients in the Vascular Study Group of New England PVI database (2010-2014), we identified 365 patients treated for lower extremity ALI who were 5:1 frequency matched (by procedure year and arterial segments treated) to 1808 patients treated for critical limb ischemia. ALI patients treated with PVI had high burden of atherosclerotic risk factors and were more likely to have had prior ipsilateral revascularizations. ALI patients were less likely to be treated with self-expanding stents and more likely to undergo thrombolysis than patients with critical limb ischemia. In multivariable analysis, ALI was associated with higher technical failure (odds ratio 1.7, 95% confidence interval, 1.1%-2.5%), increased rate of distal embolization (odds ratio 2.7, 95% confidence interval, 1.5%-4.9%), longer length of stay (means ratio 1.6, 95% confidence interval, 1.4%-1.8%), and higher in-hospital mortality (odds ratio 2.8, 95% confidence interval, 1.3%-5.9%). ALI was not associated with risk of major amputation or mortality at 1 year. In a multicenter cohort of patients treated with PVI, we found that ALI patients selected for treatment with endovascular techniques experienced greater short-term adverse events but similar long-term outcomes as their critical limb ischemia counterparts. Further studies are needed to refine the selection of ALI patients who are best served by PVI. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  2. Effects on Pulmonary Vascular Mechanics of Two Different Lung-Protective Ventilation Strategies in an Experimental Model of Acute Respiratory Distress Syndrome.

    PubMed

    Santos, Arnoldo; Gomez-Peñalver, Eva; Monge-Garcia, M Ignacio; Retamal, Jaime; Borges, João Batista; Tusman, Gerardo; Hedenstierna, Goran; Larsson, Anders; Suarez-Sipmann, Fernando

    2017-11-01

    To compare the effects of two lung-protective ventilation strategies on pulmonary vascular mechanics in early acute respiratory distress syndrome. Experimental study. University animal research laboratory. Twelve pigs (30.8 ± 2.5 kg). Acute respiratory distress syndrome was induced by repeated lung lavages and injurious mechanical ventilation. Thereafter, animals were randomized to 4 hours ventilation according to the Acute Respiratory Distress Syndrome Network protocol or to an open lung approach strategy. Pressure and flow sensors placed at the pulmonary artery trunk allowed continuous assessment of pulmonary artery resistance, effective elastance, compliance, and reflected pressure waves. Respiratory mechanics and gas exchange data were collected. Acute respiratory distress syndrome led to pulmonary vascular mechanics deterioration. Four hours after randomization, pulmonary vascular mechanics was similar in Acute Respiratory Distress Syndrome Network and open lung approach: resistance (578 ± 252 vs 626 ± 153 dyn.s/cm; p = 0.714), effective elastance, (0.63 ± 0.22 vs 0.58 ± 0.17 mm Hg/mL; p = 0.710), compliance (1.19 ± 0.8 vs 1.50 ± 0.27 mL/mm Hg; p = 0.437), and reflection index (0.36 ± 0.04 vs 0.34 ± 0.09; p = 0.680). Open lung approach as compared to Acute Respiratory Distress Syndrome Network was associated with improved dynamic respiratory compliance (17.3 ± 2.6 vs 10.5 ± 1.3 mL/cm H2O; p < 0.001), driving pressure (9.6 ± 1.3 vs 19.3 ± 2.7 cm H2O; p < 0.001), and venous admixture (0.05 ± 0.01 vs 0.22 ± 0.03, p < 0.001) and lower mean pulmonary artery pressure (26 ± 3 vs 34 ± 7 mm Hg; p = 0.045) despite of using a higher positive end-expiratory pressure (17.4 ± 0.7 vs 9.5 ± 2.4 cm H2O; p < 0.001). Cardiac index, however, was lower in open lung approach (1.42 ± 0.16 vs 2.27 ± 0.48 L/min; p = 0.005). In this experimental model, Acute

  3. Systemic lupus erythematosus in a multiethnic US cohort (LUMINA L II): relationship between vascular events and the use of hormone replacement therapy in postmenopausal women.

    PubMed

    Fernández, Mónica; Calvo-Alén, Jaime; Bertoli, Ana M; Bastian, Holly M; Fessler, Barri J; McGwin, Gerald; Reveille, John D; Vilá, Luis M; Alarcón, Graciela S

    2007-10-01

    To examine the influence of hormone replacement therapy (HRT) in the occurrence of vascular arterial and venous thrombotic events in postmenopausal women with systemic lupus erythematosus (SLE). SLE women aged > or =16 years, disease duration < or =5 years from LUMINA, a multiethnic, longitudinal outcome study, were included. Menopause was defined at disease onset as the presence of amenorrhea >6 months and/or oophorectomy, and/or increased follicle stimulating hormone values, and/or HRT use regardless of the presence or absence of climacteric symptoms (hot flashes). Patients were divided into HRT ever users and nonusers. Patients with positive antiphospholipid antibodies (n = 9) or vascular arterial events (n = 1) occurring before HRT use were excluded. The occurrence of vascular arterial and venous thrombotic events was compared between HRT users and HRT nonusers and its role examined by logistic regression after adjusting for "confounding by indication" using propensity score or logistic regression analyses. Seventy-two postmenopausal women, 32 (44%) HRT users and 40 (56%) HRT nonusers, were studied. HRT use was associated with fewer vascular arterial but not venous thrombotic events (P = 0.021) in the univariable analyses. However, after adjusting for the propensity score, HRT use was no longer significant (P = 0.064). Comparable results were obtained by logistic regression. HRT use was not associated with the occurrence of vascular arterial events in the LUMINA patients. HRT use in women with SLE should be individualized, but our data suggest its use may be safe if antiphospholipid antibodies are not present or vascular arterial events have not previously occurred.

  4. Imatinib attenuates inflammation and vascular leak in a clinically relevant two-hit model of acute lung injury.

    PubMed

    Rizzo, Alicia N; Sammani, Saad; Esquinca, Adilene E; Jacobson, Jeffrey R; Garcia, Joe G N; Letsiou, Eleftheria; Dudek, Steven M

    2015-12-01

    Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), an illness characterized by life-threatening vascular leak, is a significant cause of morbidity and mortality in critically ill patients. Recent preclinical studies and clinical observations have suggested a potential role for the chemotherapeutic agent imatinib in restoring vascular integrity. Our prior work demonstrates differential effects of imatinib in mouse models of ALI, namely attenuation of LPS-induced lung injury but exacerbation of ventilator-induced lung injury (VILI). Because of the critical role of mechanical ventilation in the care of patients with ARDS, in the present study we pursued an assessment of the effectiveness of imatinib in a "two-hit" model of ALI caused by combined LPS and VILI. Imatinib significantly decreased bronchoalveolar lavage protein, total cells, neutrophils, and TNF-α levels in mice exposed to LPS plus VILI, indicating that it attenuates ALI in this clinically relevant model. In subsequent experiments focusing on its protective role in LPS-induced lung injury, imatinib attenuated ALI when given 4 h after LPS, suggesting potential therapeutic effectiveness when given after the onset of injury. Mechanistic studies in mouse lung tissue and human lung endothelial cells revealed that imatinib inhibits LPS-induced NF-κB expression and activation. Overall, these results further characterize the therapeutic potential of imatinib against inflammatory vascular leak. Copyright © 2015 the American Physiological Society.

  5. Acute coronary disease Athero-Inflammation: Therapeutic approach

    PubMed Central

    Altman, Raul

    2003-01-01

    Antithrombotic therapy is the cornerstone of the treatment of acute coronary syndromes, but there is now evidence which indicates that by blocking inflammation, thrombosis and thus, acute coronary events, could be lowered. The concept of athero-inflammation emerges as the meeting point of different morbidities; dyslipemia, diabetes, hypertension, obesity, immunity, infection, hyperhomocyteinemia, smoking, etc. usual named as risk factors. Thus, beside specific drugs, earliest treatment, in the stage of inflammation, using anti-inflammatory drugs, should be considered since in patients with increased risk of acute coronary process are likely to have many point of origen throughout the coronary arteries. There are a body of evidences for supporting the potential of anti-inflammatory therapy to the prevention of inflammation and atherosclerosis. COX-2 inhibition may decrease endothelial inflammation reducing monocytes infiltration improving vascular cells function, plaque stability and probably resulting in a decrease of coronary atherothrombotic events. Trials including large numbers of patients in prospective double-blind randomized studies worthwhile to confirm the efficacy of NSAID, mainly, COX-2 inhibitors, together with aspirin in the prevention of coronary events in patients with acute coronary disease. PMID:12904261

  6. Preoperative antihypertensive medication intake and acute kidney injury after major vascular surgery.

    PubMed

    Duceppe, Emmanuelle; Lussier, Anne-Renee; Beaulieu-Dore, Roxane; LeManach, Yannick; Laskine, Mikhael; Fafard, Josee; Durand, Madeleine

    2018-06-01

    Postoperative acute kidney injury (AKI) is frequent after major vascular surgery and is associated with significant morbidity and mortality. It remains unclear whether the administration of combined oral antihypertensive medications on the day of surgery can increase the risk of postoperative AKI. We performed a retrospective cohort study of hypertensive patients undergoing elective major vascular surgery to determine the association between the number of antihypertensive medications continued on the morning of surgery and AKI at 48 hours postoperatively. A total of 406 patients who had undergone suprainguinal vascular surgery were included, and 10.3% suffered postoperative AKI. In multivariable analysis, the number of antihypertensive medications taken on the morning of surgery was independently associated with AKI (P = .026). Compared with patients who took no medication, taking one medication (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 0.68-3.75) and taking two or more medications (aOR, 2.70; 95% CI, 1.13-6.44) were associated with a 1.6-fold and 2.7-fold increased risk of postoperative AKI, respectively. Other predictors of AKI were suprarenal surgery (aOR, 3.37; 95% CI, 1.53-7.44), age (aOR, 2.29 per 10 years; 95% CI, 1.40-3.74), length of surgery (aOR, 1.40 per 1 hour; 95% CI, 1.10-1.76), hemoglobin drop (aOR, 1.37 per 10 g/L; 95% CI, 1.10-1.74), and history of coronary artery disease (aOR, 2.33; 95% CI, 1.08-5.00). In patients undergoing major vascular surgery who are treated with chronic antihypertensive therapy, the administration of antihypertensive drugs on the morning of surgery is independently associated with an increased risk of postoperative AKI. Further prospective studies are needed to confirm this finding. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  7. Understanding Smoking after Acute Illness: An Application of the Sentinel Event Method

    PubMed Central

    Abar, Beau; Bock, Beth; Chapman, Gretchen; Boudreaux, Edwin D.

    2016-01-01

    The Sentinel Event Theory provides a stepwise approach for building models to understand how negative events can spark health behavior change. This study tested a preliminary model using the Sentinel Events Method in a sample (N = 300) of smokers who sought care for acute cardiac symptoms. Patients completed measures on: smoking-related causal attribution, perceived severity of the acute illness event, illness-related fear, and intentions to quit smoking. Patients were followed up one week after the health event and a 7 day time line follow back (TLFB) was completed to determine abstinence from tobacco. Structural equation models were performed using average predictor scale scores at baseline, as well as three different time anchors for ratings of illness severity and illness-related fear. Quit intentions, actual illness severity, and age were consistent, positive, independent predictors of 7 day point prevalence abstinence. Additional research on the influences of perceptions and emotional reactions is warranted. PMID:25563437

  8. Preconditioning Shields Against Vascular Events in Surgery (SAVES), a multicentre feasibility trial of preconditioning against adverse events in major vascular surgery: study protocol for a randomised control trial.

    PubMed

    Healy, Donagh; Clarke-Moloney, Mary; Gaughan, Brendan; O'Daly, Siobhan; Hausenloy, Derek; Sharif, Faisal; Newell, John; O'Donnell, Martin; Grace, Pierce; Forbes, John F; Cullen, Walter; Kavanagh, Eamon; Burke, Paul; Cross, Simon; Dowdall, Joseph; McMonagle, Morgan; Fulton, Greg; Manning, Brian J; Kheirelseid, Elrasheid A H; Leahy, Austin; Moneley, Daragh; Naughton, Peter; Boyle, Emily; McHugh, Seamus; Madhaven, Prakash; O'Neill, Sean; Martin, Zenia; Courtney, Donal; Tubassam, Muhammed; Sultan, Sherif; McCartan, Damian; Medani, Mekki; Walsh, Stewart

    2015-04-23

    levels in the first 3 days post-operatively. Secondary outcome measures include length of hospital and critical care stay, unplanned critical care admissions, death, myocardial infarction, stroke, mesenteric ischaemia and need for renal replacement therapy (within 30 days of surgery). RIPC is novel intervention with the potential to significantly improve perioperative outcomes. This trial will provide the first evaluation of RIPC's ability to reduce adverse clinical events following major vascular surgery. www.clinicaltrials.gov NCT02097186 Date Registered: 24 March 2014.

  9. Genetic and Non-Genetic Factors Affecting the Quality of Anticoagulation Control and Vascular Events in Atrial Fibrillation.

    PubMed

    Park, Yun Kyung; Lee, Mi Ji; Kim, Jae Ha; Lee, Jin Soo; Park, Rae Woong; Kim, Gyeong-Moon; Chung, Chin-Sang; Lee, Kwang Ho; Kim, June Soo; Lee, Soo-Youn; Bang, Oh Young

    2017-06-01

    Warfarin has a narrow therapeutic window. We hypothesized that genetic factors related to warfarin metabolism (CYP2C9) and activity (VKORC1) would show stronger associations than modifiable factors with the quality of anticoagulation control and risks for thromboembolism and hemorrhage. In this retrospective cohort analysis, clinical and genetic data were collected from 380 patients with atrial fibrillation (AF) who were followed for an average observation period of 4 years. We evaluated the factors associated with time in therapeutic range (TTR, international normalized ratio [INR]: 2-3) and vascular events (either thromboembolic or hemorrhagic), including both genetic (CYP2C9 and VKORC1 genotype) and modifiable factors (anticoagulation service and warfarin dose assessment interval). The genotypic frequency of CYP2C9*3 (rs1057910) was 9.5% and that of VKORC1 1173C>T (rs9934438) was 16.3%. TTR showed dependence on VKORC1 polymorphism: TTR was higher in carriers of the VKORC1 1173C>T than of the VKORC1 TT genotype (61.7 ± 16.0% versus 56.7 ± 17.4%, P = .031). Multivariate testing showed that the VKORC1 genotype and anticoagulation service were independently related to labile INRs (TTR <65%). Vascular events were observed in 66 patients (18.4%) during the study period. A Cox proportional hazard model showed that the use of anticoagulation service and patients' characteristics, such as AF-thromboembolic risk (CHA 2 DS 2 -VASc score: Congestive heart failure, Hypertension, Age 75 years or older, Diabetes mellitus, previous Stroke or transient ischemic attack, Vascular disease, Age 65 to 74 years, female) and consequence (neurologic disability), but not genetic factors, were independently associated with vascular events. Both genetic factor (VKORC1 genotype) and clinical efforts (anticoagulation service) influenced the quality of anticoagulation control. However, clinical events were more strongly associated with patient characteristics and clinical

  10. Effects of Vascular and Nonvascular Adverse Events and of Extended-Release Niacin With Laropiprant on Health and Healthcare Costs.

    PubMed

    Kent, Seamus; Haynes, Richard; Hopewell, Jemma C; Parish, Sarah; Gray, Alastair; Landray, Martin J; Collins, Rory; Armitage, Jane; Mihaylova, Borislava

    2016-07-01

    Extended-release niacin with laropiprant did not significantly reduce the risk of major vascular events and increased the risk of serious adverse events in Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE), but its net effects on health and healthcare costs are unknown. 25 673 participants aged 50 to 80 years with previous cardiovascular disease were randomized to 2 g of extended-release niacin with 40 mg of laropiprant daily versus matching placebo, in addition to effective statin-based low-density lipoprotein cholesterol-lowering treatment. The net effects of niacin-laropiprant on quality-adjusted life years and hospital care costs (2012 UK £; converted into US $ using purchasing power parity index) during 4 years in HPS2-THRIVE were evaluated using estimates of the impact of serious adverse events on health-related quality of life and hospital care costs. During the study, participants assigned niacin-laropiprant experienced marginally but not statistically significantly lower survival (0.012 fewer years [standard error (SE) 0.007]), fewer quality-adjusted life years (0.023 [SE 0.007] fewer using UK EQ-5D scores; 0.020 [SE 0.006] fewer using US EQ-5D scores) and accrued greater hospital costs (UK £101 [SE £37]; US $145 [SE $53]). Stroke, heart failure, musculoskeletal events, gastrointestinal events, and infections were associated with significant decreases in health-related quality of life in both the year of the event and in subsequent years. All serious vascular and nonvascular events were associated with substantial increases in hospital care costs. In HPS2-THRIVE, the addition of extended-release niacin-laropiprant to statin-based therapy reduced quality of life-adjusted survival and increased hospital costs. URL: http://clinicaltrials.gov. Unique identifier: NCT00461630. © 2016 American Heart Association, Inc.

  11. Influence of fitness and age on the endothelial response to acute inflammation.

    PubMed

    Schroeder, Elizabeth C; Lane-Cordova, Abbi D; Ranadive, Sushant M; Baynard, Tracy; Fernhall, Bo

    2018-06-01

    What is the central question of the study? What are the effects of age and fitness on the vascular response to acute inflammation in younger and older adults? What is the main finding and its importance? In older adults, cardiorespiratory fitness level has a differential impact on endothelial function after acute inflammation. Compared with older adults with low fitness, older, moderately fit adults have a greater decrease in endothelial function, similar to that of younger adults. These findings have important implications in support of the beneficial effects of higher cardiorespiratory fitness in maintaining vascular reactivity and the ability to respond to stressors. Inflammation is associated with greater risk of cardiovascular events and reduced vascular function with ageing. Higher cardiorespiratory fitness is associated with lower risk of cardiovascular events and better vascular function. We evaluated the role of fitness in the vascular response to acute inflammation in 26 younger adults (YA) and 62 older adults (OA). We used an influenza vaccine to induce acute inflammation. Blood pressure, flow-mediated dilatation (FMD), augmentation index, carotid elastic modulus and inflammatory markers were measured before and 24 h after vaccination. Peak oxygen uptake was measured via a treadmill test. 'Fit' was defined as a peak oxygen uptake greater than the age- and sex-determined 50th percentile according to the American College of Sports Medicine. An interaction effect existed for the FMD response during acute inflammation (P < 0.05). The YA (low fit, from 11.5 ± 1.8 to 9.2 ± 1.3%; moderately fit, from 11.9 ± 0.8 to 9.0 ± 0.8%) and moderately fit OA (from 7.5 ± 1.0 to 3.9 ± 0.8%) had similar reductions in FMD at 24 h (P < 0.05). Low-fit OA did not reduce FMD at 24 h (from 5.5 ± 0.4 to 5.2 ± 0.5%, P > 0.05). The reduction in FMD in YA was similar between fitness groups (P > 0.05). All groups had similar reductions in mean

  12. Cardiovascular events in chronic dialysis patients: emphasizing the importance of vascular disease prevention.

    PubMed

    Paraskevas, Kosmas I; Kotsikoris, Ioannis; Koupidis, Sotirios A; Tzovaras, Alexandros A; Mikhailidis, Dimitri P

    2010-12-01

    Cardiovascular disease is the leading cause of death in both chronic kidney disease and peritoneal dialysis/hemodialysis patients. Vascular disease prevention in these patients is therefore important to reduce the incidence of cardiovascular events and the high morbidity and mortality. This Editorial discusses the traditional, (1) smoking, (2) dyslipidemia, (3) body mass index, (4) glycemic control and (5) blood pressure, and non-traditional, (1) anemia, (2) vitamin D/hyperparathyroidism, (3) calcium/phosphorus metabolism and (4) magnesium, risk factors in renal patients. Current evidence does not support routine statin use and antiplatelet medication to dialysis patients. Patient compliance and adherence to proposed measures could be essential to reduce cardiovascular events and mortality rates in this high-risk population.

  13. Patent foramen ovale transcatheter closure vs. medical therapy on recurrent vascular events: a systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Rengifo-Moreno, Pablo; Palacios, Igor F; Junpaparp, Parichart; Witzke, Christian F; Morris, D Lynn; Romero-Corral, Abel

    2013-11-01

    In patients with cryptogenic stroke, transcatheter (TC) closure of a patent foramen ovale (PFO) has not been shown to better prevent recurrent vascular events than medical therapy. However, randomized controlled trials (RCT) to date have included few vascular events, and lack of power has been raised as an important concern. To conduct a systematic review and meta-analysis of existing RCT published studies assessing the recurrence of vascular events after TC PFO closure when compared to medical therapy. Using the search terms "patent foramen ovale", "PFO", "stroke", "percutaneous closure" and "transcatheter closure", Medline, Pubmed, Embase, and Cochrane databases were reviewed from inception through April 2013, with no language restrictions. Only studies in adult humans were considered. Additional references were obtained from the bibliographies of studies reviewed. The following criteria were used for study selection: 1) randomized controlled trial, 2) subjects were adult patients with cryptogenic stroke who were randomized to TC PFO closure or medical treatment (antiplatelet therapy and/or anticoagulation), and 3) reported outcomes included cardiac death, all death, stroke, transient ischemic attack, and peripheral embolism. Methodological and descriptive data, adverse events (including raw data and risk estimates), as well as procedural success and complications were abstracted in duplicate from each study independently, and agreement was tested. We followed rigorously the recommended guidelines for reporting and conducting and assessing quality of meta-analysis of RCT. The primary endpoints pre-specified in advance were recurrent vascular events, and composite endpoint of death, and recurrent vascular events. Three studies were identified as meeting selection criteria. These included a total of 2,303 patients, with 1,150 patients randomized to TC PFO closure and 1,153 patients randomized to medical therapy. Mean follow-up was 3.5 years. Baseline

  14. Effect of Intravitreal Anti-Vascular Endothelial Growth Factor Therapy on the Risk of Arterial Thromboembolic Events: A Meta-Analysis

    PubMed Central

    Lu, Guo-Cai; Wei, Rui-Li

    2012-01-01

    Background Intravitreal anti-vascular endothelial growth factor (VEGF) monoclonal antibodies are used in ocular neovascular diseases. A consensus has emerged that intravenous anti-VEGF can increase the risk of arterial thromboembolic events. However, the role of intravitreal anti-VEGF in arterial thromboembolism is controversial. Therefore, we did a systematic review and meta-analysis to investigate the effects of intravitreal anti-VEGF on the risk of arterial thromboembolic events. Methods Electronic databases were searched to identify relevant randomized clinical trials comparing intravitreal anti-VEGF with controls. Criteria for inclusion in our meta-analysis included a study duration of no less than 12 months, the use of a randomized control group not receiving any intravitreal active agent, and the availability of outcome data for arterial thromboembolic events, myocardial infarction, cerebrovascular accidents, and vascular death. The risk ratios and 95% CIs were calculated using a fixed-effects or random-effects model, depending on the heterogeneity of the included studies. Results A total of 4942 patients with a variety of ocular neovascular diseases from 13 randomized controlled trials were identified and included for analysis. There was no significant difference between intravitreal anti-VEGF and control in the risk of all events, with risk ratios of 0.87 (95% CI, 0.64 to 1.19) for arterial thromboembolic events, 0.96 (95% CI, 0.55–1.68) for cerebrovascular accidents, 0.69 (95% CI 0.40–1.21) for myocardial infarctions, and 0.68 (95% CI, 0.37–1.27) for vascular death. Conclusions The strength evidence suggests that the intravitreal use of anti-VEGF antibodies is not associated with an increased risk of arterial thromboembolic events. PMID:22829940

  15. Rs964184 (APOA5-A4-C3-A1) is related to elevated plasma triglyceride levels, but not to an increased risk for vascular events in patients with clinically manifest vascular disease.

    PubMed

    van de Woestijne, Anton P; van der Graaf, Yolanda; de Bakker, Paul I W; Asselbergs, Folkert W; Spiering, Wilko; Visseren, Frank L J

    2014-01-01

    Single nucleotide polymorphisms in the APOA5-A4-C3-A1 gene complex are associated with elevated plasma triglycerides and elevated vascular risk in healthy populations. In patients with clinically manifest vascular disease, hypertriglyceridemia and metabolic syndrome are frequently present, but the contribution of these single nucleotide polymorphisms to plasma triglycerides, effect modification by obesity and risk of recurrent vascular events is unknown in these patients. Prospective cohort study of 5547 patients with vascular disease. Rs964184 (APOA5-A4-C3-A1 gene complex) was genotyped, and we evaluated the relation with plasma lipid levels, presence of metabolic syndrome and the risk for new vascular events. The minor allele of rs964184 was strongly associated with log plasma triglycerides (β 0.12; 95%CI 0.10-0.15, p = 1.1*10(-19)), and was also associated with 0.03 mmol/L lower high-density lipoprotein-cholesterol (95%CI 0.01-0.04), and 0.14 mmol/L higher non-high-density lipoprotein-cholesterol (95%CI 0.09-0.20). The minor allele frequency increased from 10.9% in patients with plasma triglycerides <1 mmol/L to 24.6% in patients with plasma triglycerides between 4 and 10 mmol/L. The relation between rs964184 and plasma triglycerides was modified by body mass index in patients with one minor allele (β 0.02; (95%CI -0.04-0.09) if body mass index <24 kg/m2, β 0.17 (95%CI 0.12-0.22) if body mass index >27 kg/m2, p for interaction = 0.02). The prevalence of the metabolic syndrome increased from 52% for patients with two copies of the major allele to 62% for patients with two copies of the minor allele (p = 0.01). Rs964184 was not related with recurrent vascular events (HR 0.99; 95%CI 0.86-1.13). The single nucleotide polymorphism rs964184 (APOA5-A4-C3-A1) is associated with elevated plasma triglycerides concentrations in patients with clinically manifest vascular disease. In carriers of one minor allele, the effect on plasma triglycerides was modified

  16. Risk of Digital Vascular Events in Scleroderma Patients Who Have Both Anticentromere and Anti-Interferon-Inducible Protein 16 Antibodies.

    PubMed

    McMahan, Zsuzsanna H; Wigley, Frederick M; Casciola-Rosen, Livia

    2017-06-01

    To evaluate whether scleroderma patients who are double-positive for anti-interferon-inducible protein 16 (anti-IFI-16) antibodies and anticentromere (anti-CENP) antibodies are at increased risk for significant digital vascular events relative to patients positive for anti-CENP antibodies alone. Sera from 165 scleroderma patients who tested positive for anti-CENP antibodies upon clinical evaluation were reassayed for both anti-CENP and anti-IFI-16 antibodies using enzyme-linked immunosorbent assay testing. Patients who were positive for anti-CENP antibodies alone were then compared to patients who were double-positive for both anti-IFI-16 and anti-CENP antibodies. The association between a history of significant digital vascular events (digital pits, ischemic digital ulcers, and/or gangrene) and double-positive antibody status was examined using chi-square tests. After completion of univariate analysis, multivariable analyses were done to adjust for clinically relevant covariates. Of the 165 anti-CENP antibody positive patients, 21 (12.7%) also had anti-IFI-16 antibodies. Patients who were double-positive for anti-CENP and anti-IFI-16 antibodies were more likely to have had digital pits, ischemic digital ulcers, and/or gangrene (P = 0.03). After adjustment for clinically relevant covariates (age, cutaneous subtype, disease duration, and smoking), double-positive patients remained at significantly higher odds of having severe Raynaud's phenomenon (odds ratio 3.5 [95% confidence interval 1.1-11.1]; P = 0.03). Scleroderma patients who are double-positive for antibodies recognizing CENP and IFI-16 are significantly more likely to have significant digital vascular events during the course of their disease. This study provides further evidence that anti-CENP and anti-IFI-16 antibodies are disease biomarkers that may be used for risk stratification of vascular events in scleroderma. © 2016, American College of Rheumatology.

  17. Consumption of a flavonoid-rich açai meal is associated with acute improvements in vascular function and a reduction in total oxidative status in healthy overweight men.

    PubMed

    Alqurashi, Randah M; Galante, Laura A; Rowland, Ian R; Spencer, Jeremy Pe; Commane, Daniel M

    2016-11-01

    Açai (Euterpe oleracea) is a polyphenol-rich fruit marketed as beneficial for health. Experimental data showing improvements in health markers arising from açai consumption in humans is limited. The objective of the present study was to investigate the effect of açai consumption on acute changes in vascular function and on other disease risk markers, including postprandial plasma insulin, glucose, and oxidative stress. Twenty-three healthy male volunteers, aged 30-65 y and with a body mass index (in kg/m 2 ) of 25-30, completed a randomized, controlled, high-fat challenge, double-blind, crossover, acute dietary intervention trial. The volunteers consumed either an açai-based smoothie (AS) or a macronutrient-matched control smoothie (PS) together with a high-fat breakfast meal challenge. The primary endpoint was the assessment of endothelial function in the brachial artery by flow-mediated dilatation (FMD). The acute consumption of an AS containing 694 mg total phenolics improved vascular function, with postprandial increases in FMD from baseline of 1.4% at 2 h compared with 0.4% after consumption of the PS (P = 0.001) and increases at 6 h of 0.8% for the AS compared with -0.3% for the PS (P < 0.001). There was also a significantly lower incremental area under the curve (iAUC) for total peroxide oxidative status after açai consumption relative to the control. No significant changes were observed in blood pressure, heart rate, or postprandial glucose response. However, the first postprandial insulin peak (after breakfast) and the iAUC for insulin were elevated for the AS relative to the PS. In this acute study in overweight men, açai consumption was associated with improvements in vascular function, which may lower the risk of a cardiovascular event. Future intervention studies, perhaps with a chronic design, in wider populations and with other biomarkers of disease risk are needed to fully elucidate the benefits of açai to health. This trial was registered at

  18. Association of Antihypertensive Medication Adherence With Healthcare Use and Medicaid Expenditures for Acute Cardiovascular Events.

    PubMed

    Yang, Zhuo; Howard, David H; Will, Julie; Loustalot, Fleetwood; Ritchey, Matthew; Roy, Kakoli

    2016-05-01

    We assessed the impact of antihypertensive medication (AHM) adherence on the incidence and associated Medicaid costs of acute cardiovascular disease (CVD) events among Medicaid beneficiaries. The study cohort (n=59,037) consists of nonelderly adults continuously enrolled (36 mo and above) in a Medicaid fee-for-service program. AHM adherence was calculated using the medication possession ratio (MPR) and stratified to low (MPR<60%), moderate (60%≤MPR<80%), and high (MPR≥80%) levels. We used a proportional hazard model to estimate risk for acute CVD events and generalized linear models to estimate Medicaid per-patient-per-year costs. Low and moderate adherence subgroups had about 1.8 and 1.4 times higher risk of acute CVD events, compared with high adherence subgroup. By adherence level, Medicaid per-patient per-year costs for (1) CVD-related emergency department visits and hospitalizations were $661 (low), $479 (moderate), and $343 (high) and (2) AHMs were $430 (low), $604 (moderate), and $664 (high). Costs for CVD events and AHMs combined were similar across adherence subgroups. Lower adherence to AHM was associated with progressively higher CVD risk. The increase in medication cost from higher AHM adherence was offset solely by reduced Medicaid spending on acute CVD events.

  19. Does the circadian pattern for acute cardiac events presentation vary with fasting?

    PubMed

    Al Suwaidi, J; Bener, A; Gehani, A A; Behair, S; Al Mohanadi, D; Salam, A; Al Binali, H A

    2006-01-01

    Over one billion Muslims fast worldwide during the month of Ramadan. The impact of fasting on circadian presentation with acute cardiac events is unknown. To determine if fasting has any effect on the circadian presentation of acute cardiac events. A prospective study in a general hospital. Patients with acute coronary events were divided into two groups based on the history of fasting. Information about age, gender, cardiovascular risk factor profiles and outcome was collected. The relationship of time of presentation of initial symptoms with fasting was evaluated using Student's t-test, Mann-Whitney U-test and chi2 analysis. Of the 1019 patients hospitalized during the study period, 162 were fasting. Although, fasting patients were more likely to present to the emergency department in the time periods 5-6 AM (10.5% vs 6.3%) and 11 PM (11.1% vs 7.1%) and were less likely to present in the time periods 1-2 PM (3.7% vs 7.2%) and 5-6 PM (3.7% vs 7.0%); these differences were not statistically significant. Fasting patients were less likely to have their symptoms start between 5 and 8 AM (11.1% vs 19.4%) and more likely to have symptoms between 5 and 6 PM (11.1% vs 6.0%) and 3 and 4 AM (11.1% vs 6.9%). These differences for time of initial symptoms were statistically significant (P=0.002). Exogenous factors associated with fasting, namely, the changes in food intake and/or sleep timings, affect the circadian rhythm and influence the timing of presentation of acute coronary events.

  20. [Management of acute and subacute clinical situations by interventional radiology: non-vascular interventions and treatment for hemoptysis].

    PubMed

    Nemes, Balázs; Doros, Attila

    2015-04-26

    Interventional radiology provides fast, straightforward and tolerable solutions for many medical problems including acute and subacute situations. Aspiration and drainage of fluid collections, biliary and endourologic interventions and gastrointestinal interventions are parts of non-vascular interventions. In addition, the authors discuss in detail interventional radiological treatment options in patients with hemoptysis. In acute cases interventions must be performed within 12-24 hours. For background, an everyday 24 hours service should be provided with well-trained personnel, high quality equipment and devices, and a reasonable financial reimbursement should be included, too. Multidisciplinary teamwork, consultations, consensus in indications and structured education should make these centers function most effectively.

  1. Intraosseous vascular access in disasters and mass casualty events: A review of the literature.

    PubMed

    Burgert, James M

    2016-01-01

    The intraosseous (IO) route of vascular access has been increasingly used to administer resuscitative fluids and drugs to patients in whom reliable intravenous (IV) access could not be rapidly or easily obtained. It is unknown that to what extent the IO route has been used to gain vascular access during disasters and mass casualty events. The purpose of this review was to examine the existing literature to answer the research question, "What is the utility of the IO route compared to other routes for establishing vascular access in patients resulting from disasters and mass casualty events?" Keyword-based online database search of PubMed, CINAHL, and the Cochrane Database of Systematic Reviews. University-based academic research cell. Included evidence were randomized and nonrandomized trials, systematic reviews with and without meta-analysis, case series, and case reports. Excluded evidence included narrative reviews and expert opinion. Not applicable. Of 297 evidence sources located, 22 met inclusion criteria. Located evidence was organized into four categories including chemical agent poisoning, IO placement, while wearing chemical protective clothing (PPE), military trauma, and infectious disease outbreak. Evidence indicates that the IO route of infusion is pharmacokinetically equal to the IV route and superior to the intramuscular (IM) and endotracheal routes for the administration of antidotal drugs in animal models of chemical agent poisoning while wearing full chemical PPE. The IO route is superior to the IM route for antidote administration during hypovolemic shock. Civilian casualties of explosive attacks and mass shootings would likely benefit from expanded use of the IO route and military resuscitation strategies. The IO route is useful for fluid resuscitation in the management of diarrheal and hemorrhagic infectious disease outbreaks.

  2. Identifying youth at risk for difficulties following a traumatic event: pre-event factors are associated with acute symptomatology.

    PubMed

    Goslin, Megan C; Stover, Carla Smith; Berkowitz, Steven; Marans, Steven

    2013-08-01

    This study examined factors related to children's acute symptoms following a potentially traumatic event (PTE) to more clearly identify domains that should be included in screenings of youth exposed to a PTE. In particular, the authors examined whether trauma category (i.e., sexual abuse/disclosure of abuse, intentionally perpetrated traumas other than sexual abuse, and unintentional traumas) was related to symptoms after controlling for other relevant factors. Participants were 112 youth presenting for clinical evaluation within a month of a PTE and their nonoffending caregivers. Using data from baseline assessments collected as part of a randomized controlled trial of a secondary prevention program, the following factors were tested in 3 hierarchical regression models: index PTE category, history of traumatic exposure, preindex event functioning, and parenting behaviors. Prior trauma exposure, preindex event functioning, and hostile parenting were uniquely related to children's symptoms in the acute posttraumatic period after controlling for time since the event and child age, but trauma category was not. Implications for identifying and referring children at high risk for poor outcomes in the early aftermath of a PTE are discussed. An exclusive focus on the event is insufficient and more comprehensive understanding of the child and family is required. Copyright © 2013 International Society for Traumatic Stress Studies.

  3. Cost-Effectiveness Comparison of Breast Cancer Screening and Vascular Event Primary Prevention with Aspirin in Wales

    ERIC Educational Resources Information Center

    Morgan, Gareth

    2011-01-01

    Aim: For the first time, this article presents a cost-effectiveness comparison of a breast cancer screening programme with a possible health education programme with aspirin for vascular event primary prevention. Background: Breast cancer screening is a well established part of cancer control programmes yet recent evidence on this intervention has…

  4. Acute impact of conventional and eccentric cycling on platelet and vascular function in patients with chronic heart failure.

    PubMed

    Haynes, Andrew; Linden, Matthew D; Chasland, Lauren C; Nosaka, Kazunori; Maiorana, Andrew; Dawson, Ellen A; Dembo, Lawrence H; Naylor, Louise H; Green, Daniel J

    2017-06-01

    Evidence-based guidelines recommend exercise therapy for patients with chronic heart failure (CHF). Such patients have increased atherothrombotic risk. Exercise can transiently increase platelet activation and reactivity and decrease vascular function in healthy participants, although data in CHF are scant. Eccentric (ECC) cycling is a novel exercise modality that may be particularly suited to patients with CHF, but the acute impacts of ECC cycling on platelet and vascular function are currently unknown. Our null hypothesis was that ECC and concentric (CON) cycling, performed at matched external workloads, would not induce changes in platelet or vascular function in patients with CHF. Eleven patients with heart failure with reduced ejection fraction (HFrEF) took part in discrete bouts of ECC and CON cycling. Before and immediately after exercise, vascular function was assessed by measuring diameter and flow-mediated dilation (FMD) of the brachial artery. Platelet function was measured by the flow cytometric determination of glycoprotein IIb/IIIa activation and granule exocytosis in the presence and absence of platelet agonists. ECC cycling increased baseline artery diameter (pre: 4.0 ± 0.8 mm vs. post: 4.2 ± 0.7 mm; P = 0.04) and decreased FMD%. When changes in baseline artery diameter were accounted for, the decrease in FMD post-ECC cycling was no longer significant. No changes were apparent after CON. Neither ECC nor CON cycling resulted in changes to any platelet-function measures (all P > 0.05). These results suggest that both ECC and CON cycling, at a moderate intensity and short duration, can be performed by patients with HFrEF without detrimental impacts on vascular or platelet function. NEW & NOTEWORTHY This is the first evidence to indicate that eccentric (ECC) cycling can be performed relatively safely by patients with chronic heart failure (CHF), as it did not result in impaired vascular or platelet function compared with conventional cycling

  5. Presence of intracranial artery calcification is associated with mortality and vascular events in patients with ischemic stroke after hospital discharge: a cohort study.

    PubMed

    Bugnicourt, Jean-Marc; Leclercq, Claire; Chillon, Jean-Marc; Diouf, Momar; Deramond, Hervé; Canaple, Sandrine; Lamy, Chantal; Massy, Ziad A; Godefroy, Olivier

    2011-12-01

    Although intracranial artery calcification (IAC) has been reported to be a risk factor for ischemic stroke, the prognostic implications of IAC in stroke outcome are unknown. The purpose of this study was to determine the association between IAC and risk of vascular events and death in patients with stroke after hospital discharge. All patients with ischemic stroke over a 1-year period were included (n=302). IAC, assessed by multidetector CT, was defined as hyperdense foci (peak density>130 Hounsfield units) and assessed in the 7 major cerebral arteries. The IAC scores ranged from 0 (no calcification) to 7. Follow-up information on major clinical events (including fatal or nonfatal ischemic stroke, cardiac and peripheral artery events, and all-cause death) was obtained by means of a structured phone interview. IAC was present in 260 patients (83%). With a mean follow-up of 773±223 days, 88 major clinical events occurred in 67 patients (22%): 45 new ischemic vascular events (ischemic stroke: n=22; cardiac event: n=15; peripheral artery event: n=8) and 43 deaths from any cause. Patients with the highest IAC scores had significantly higher rates of death and vascular events than those with the lowest IAC scores (log rank test, P=0.029). In the Cox proportional hazards regression model, the IAC score was significantly associated with major clinical events (hazard ratio, 1.34; 95% CI, 1.11-1.61; P=0.002). In patients with ischemic stroke, IAC detection may constitute a simple marker of a high risk of future major clinical events.

  6. Clustering of ABCB1 and CYP2C19 Genetic Variants Predicts Risk of Major Bleeding and Thrombotic Events in Elderly Patients with Acute Coronary Syndrome Receiving Dual Antiplatelet Therapy with Aspirin and Clopidogrel.

    PubMed

    Galeazzi, Roberta; Olivieri, Fabiola; Spazzafumo, Liana; Rose, Giuseppina; Montesanto, Alberto; Giovagnetti, Simona; Cecchini, Sara; Malatesta, Gelsomina; Di Pillo, Raffaele; Antonicelli, Roberto

    2018-06-23

    The clinical efficacy of clopidogrel in secondary prevention of vascular events is hampered by marked inter-patient variability in drug response, which partially depends on genetic make-up. The aim of this pilot prospective study was to evaluate 12-month cardiovascular outcomes in elderly patients with acute coronary syndrome (ACS) receiving dual antiplatelet therapy (aspirin and clopidogrel) according to the clustering of CYP2C19 and ABCB1 genetic variants. Participants were 100 consecutive ACS patients who were genotyped for CYP2C19 (G681A and C-806T) and ABCB1 (C3435T) polymorphisms, which affect clopidogrel metabolism and bioavailability, using PCR-restriction fragment length polymorphism. They were then grouped as poor, extensive and ultra-rapid metabolisers based on the combination of CYP2C19 loss-of-function (CYP2C19*2) and gain-of-function (CYP2C19*17) alleles and ABCB1 alleles. The predictive value of each phenotype for acute vascular events was estimated based on 12-month cardiovascular outcomes. The poor metabolisers were at an increased risk of thrombotic events (OR 1.26; 95% CI 1.099-1.45; χ 2  = 5.676; p = 0.027), whereas the ultra-rapid metabolisers had a 1.31-fold increased risk of bleeding events compared with the poor and extensive metabolisers (OR 1.31; 95% CI 1.033-1.67; χ 2  = 5.676; p = 0.048). Logistic regression model, including age, sex, BMI and smoking habit, confirmed the differential risk of major events in low and ultra-rapid metabolisers. Our findings suggest that ACS patients classified as 'poor or ultra-rapid' metabolisers based on CYP2C19 and ABCB1 genotypes should receive alternative antiplatelet therapies to clopidogrel.

  7. Imaging features of non-traumatic vascular liver emergencies.

    PubMed

    Onur, Mehmet Ruhi; Karaosmanoglu, Ali Devrim; Akca, Onur; Ocal, Osman; Akpinar, Erhan; Karcaaltincaba, Musturay

    2017-05-01

    Acute non-traumatic liver disorders can originate from abnormalities of the hepatic artery, portal vein and hepatic veins. Ultrasonography and computed tomography can be used in non-traumatic acute vascular liver disorders according to patient status, indication and appropriateness of imaging modality. Awareness of the imaging findings, in the appropriate clinical context, is crucial for prompt and correct diagnosis, as delay may cause severe consequences with significant morbidity and mortality. This review article will discuss imaging algorithms, and multimodality imaging findings for suspected acute vascular disorders of the liver.

  8. Ginkgo biloba extract improved cognitive and neurological functions of acute ischaemic stroke: a randomised controlled trial

    PubMed Central

    Li, Shanshan; Zhang, Xinjiang; Fang, Qi; Zhou, Junshan; Zhang, Meijuan; Wang, Hui; Chen, Yan; Xu, Biyun; Wu, Yanfeng; Qian, Lai

    2017-01-01

    Purpose To evaluate the efficacy and safety of Ginkgo biloba extract (GBE) in acute ischaemic stroke and its impact on the recurrence of vascular events. Methods We conducted a multicentre, prospective, randomised, open label, blinded, controlled clinical trial enrollingpatients with an onset of acute stroke within 7 days from five hospitals in China Jiangsu Province. Participants were assigned to the GBE group (450 mg GBE with 100 mg aspirin daily) or the control group (100 mg aspirin daily) for 6 months. The primary outcome was the decline in the Montreal Cognitive Assessment score at 6 months. Secondary outcomes were other neuropsychological tests of cognitive and neurological function, the the incidence of adverse events and vascular events. Results 348 patients were enrolled: 179 in the GBE group and 169 in the control group. With 18 patients lost to follow-up, the dropout rate was 5.17%. Admission data between two groups were similar, but in the GBE group there was a marked slow down in the decline in the Montreal Cognitive Assessment scores (−2.77±0.21 vs −1.99±0.23, P=0.0116 (30 days); −3.34±0.24 vs −2.48±0.26, P=0.0165 (90 days); −4.00±0.26 vs −2.71±0.26, P=0.0004 (180 days)) compared with controls. The National Institutes of Health Stroke Scale scores at 12 and 30 days, the modified Rankin Scale scores for independent rate at 30, 90 and 180 days, and the Barthel Index scores at 30, 90 and 180 days in the GBE group were significantly improved compared with controls. Improvements were also observedin GBE groups for Mini-Metal State Examination scores of 30, 90 and 180 days, Webster’s digit symbol test scores at 30 days and Executive Dysfunction Index scores at 30 and 180 days. No significant differences were seen in the incidence of adverse events or vascular events. Conclusions We conclude that GBE in combination with aspirin treatment alleviated cognitive and neurological deficits after acute ischaemic stroke without increasing

  9. Association between vascular calcification assessed by simple radiography and non-fatal cardiovascular events in hemodialysis patients.

    PubMed

    Petrauskiene, Vaida; Vaiciuniene, Ruta; Bumblyte, Inga Arune; Kuzminskis, Vytautas; Ziginskiene, Edita; Grazulis, Saulius; Jonaitiene, Egle

    2016-12-01

    Vascular calcification (VC) is one of the factors associated with cardiovascular mortality in hemodialysis (HD) patients. Recommendations concerning screening for VC differ. Possible ability to prevent and reversibility of VC are major subjects on debate whether screening for VC could improve outcomes of renal patients. The objective of the study was to evaluate the significance of simple vascular calcification score (SVCS) based on plane radiographic films and to test its association with non-fatal cardiovascular events in patients on chronic HD. A study population consisted of 95 prevalent HD patients in the HD unit of Hospital of Lithuanian University of Health sciences Kaunas Clinics. Clinical data and laboratory tests information were collected from medical records. SVCS was evaluated as it is described by Adragao et al. After measurement of VC, HD patients were observed for novel non-fatal cardiovascular events. Patients were divided into two groups: SVCS≥3 (57 patients [60%]) and <3 (38 patients [40%]). The Kaplan-Meier survival curves show a significant difference in non-fatal cardiovascular events in the group with SVCS≥3 vs. <3 group (26.3% vs. 7.8%; log rank 5,49; P=0.018). Multivariate Cox regression analysis confirmed a negative impact of VC, hyperphosphatemia, and lower ejection fraction on cardiovascular events. No statistically significant differences were observed comparing parameters of Ca-P metabolism disorders between groups with different SVCS. On separate analysis, the presence of VC in hands was also associated with higher rate of novel cardiovascular events (score 0 goup-5 events [10.6%] vs. score≥1 group-13 events [27%], log rank P=0.035). VC assessed by simple and inexpensive radiological method was an independent predictor of novel non-fatal cardiovascular events in HD patients. Copyright © 2016 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  10. [Impact of isolated diastolic hypertension on new-onset cardiovascular and cerebro-vascular diseases].

    PubMed

    Xing, Fengmei; Dong, Yan; Tao, Jie; Gao, Xinying; Zhou, Jianhui; Chen, Shuohua; Ji, Chunpeng; Yao, Tao; Wu, Shouling

    2014-08-01

    To explore the impact of isolated diastolic hypertension (IDH) on new-onset cardio-cerebral vascular diseases (CVD). This cohort study involved 101 510 participants who were employees of the Kailuan Group-a state-run coal mining company, in 2006 and 2007. Among them, 6 780 subjects were diagnosed with IDH, 35 448 subjects were diagnosed with high-normal blood pressure and 19 460 subjects were diagnosed with normal tension. However, none of them had the history of either cardio-cerebral vascular disease or malignant cancer. Cardio-cerebral vascular events including cerebral infarction, cerebral hemorrhage, acute myocardial infarction were recorded every 6 months during the follow-up (47.1 ± 4.8) period. Multivariable Cox proportional hazards regression models were used to analyze the risk factors of first-ever CVD events. 1) There were 675 CVD events occurred during the follow-up period. The incidence rates of CVD events (1.7% vs. 0.9%), cerebral infarction (1.0% vs. 0.6%) and cerebral hemorrhage (0.4% vs. 0.1%) were significantly higher in IDH group than that in the normal tension group (all P < 0.05). 2) After adjustment for other established CVD risk factors, the hazards ratios became 1.67 (95% CI: 1.28-2.17) for total CVD events and 1.59 (95% CI: 1.12-2.27) for cerebral infarction and 2.67 (95% CI: 1.54-4.65) for cerebral hemorrhage in the IDH group. 3). In stratified analysis on age, after adjustment for other established CVD risk factors, the hazards ratio was 2.22 (95% CI: 1.41-3.50) for cerebral infarction in lower 60 years old group, while the it was 7.27 (95% CI: 2.58-20.42) for cerebral hemorrhage in groups older than 60 years of age. IDH was the independent risk factor for the total cardio-cerebral vascular events, on both cerebral infarction and cerebral hemorrhage. The predicted values of IDH for different CVD events were diverse on different age groups.

  11. Economic burden of cardiovascular events and fractures among patients with end-stage renal disease.

    PubMed

    Doan, Quan V; Gleeson, Michelle; Kim, John; Borker, Rohit; Griffiths, Robert; Dubois, Robert W

    2007-07-01

    To quantify direct medical costs of fractures and cardiovascular diseases among end-stage renal disease (ESRD) patients. Medicare claims data from year 2001 of the United States Renal Data System were used to quantify direct medical costs of acute episodic events (acute myocardial infarction (MI), stroke, heart valve repair, heart valve replacement, fractures) and chronic conditions (arrhythmia, peripheral vascular disease (PVD), heart valve disease (HVD), congestive heart failure (CHF), coronary heart disease, and non-acute stroke). Costs of hospitalized episodes of arrhythmia, PVD, CHF, and angina were also quantified. For acute events, costs were quantified using an episode-of-care approach. For chronic conditions, annualized costs were reported. Only costs specific to the events or conditions of interest were included and reported, in 2006 US dollars. Drug and dialysis-related costs were excluded. Diagnosis and procedure codes were used to identify these events and conditions. Among acute events analyzed as clinical episodes, PVD ($358 million) was associated with the greatest economic burden, followed by CHF, arrhythmia, angina, acute MI, heart valve replacement, hip fracture, acute stroke, heart valve repair, vertebral fracture, and pelvic fracture ($8.6 million). The cost per episode ranged from approximately $12,000 to 104,000. Among chronic conditions, CHF ($681 million) contributed the greatest economic burden; HVD ($100 million) contributed the least. The costs per patient-year ranged from $23,000 to 45,000 among chronic conditions. The costing methodology utilized could contribute to an underestimate of the economic impact of each condition; therefore these results are considered conservative. The economic burden of these selected conditions was substantial to health services payers who finance ESRD patient care. Episodic costs were high for most acute events.

  12. Management of bleeding in vascular surgery.

    PubMed

    Chee, Y E; Liu, S E; Irwin, M G

    2016-09-01

    Management of acute coagulopathy and blood loss during major vascular procedures poses a significant haemostatic challenge to anaesthetists. The acute coagulopathy is multifactorial in origin with tissue injury and hypotension as the precipitating factors, followed by dilution, hypothermia, acidemia, hyperfibrinolysis and systemic inflammatory response, all acting as a self-perpetuating spiral of events. The problem is confounded by the high prevalence of antithrombotic agent use in these patients and intraoperative heparin administration. Trials specifically examining bleeding management in vascular surgery are lacking, and much of the literature and guidelines are derived from studies on patients with trauma. In general, it is recommended to adopt permissive hypotension with a restrictive fluid strategy, using a combination of crystalloid and colloid solutions up to one litre during the initial resuscitation, after which blood products should be administered. A restrictive transfusion trigger for red cells remains the mainstay of treatment except for the high-risk patients, where the trigger should be individualized. Transfusion of blood components should be initiated by clinical evidence of coagulopathy such as diffuse microvascular bleeding, and then guided by either laboratory or point-of-care coagulation testing. Prophylactic antifibrinolytic use is recommended for all surgery where excessive bleeding is anticipated. Fibrinogen and prothrombin complex concentrates administration are recommended during massive transfusion, whereas rFVIIa should be reserved until all means have failed. While debates over the ideal resuscitative strategy continue, the approach to vascular haemostasis should be scientific, rational, and structured. As far as possible, therapy should be monitored and goal directed. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Blood groups and acute aortic dissection type III.

    PubMed

    Fatic, Nikola; Nikolic, Aleksandar; Vukmirovic, Mihailo; Radojevic, Nemanja; Zornic, Nenad; Banzic, Igor; Ilic, Nikola; Kostic, Dusan; Pajovic, Bogdan

    2017-04-01

    Acute aortic type III dissection is one of the most catastrophic events, with in-hospital mortality ranging between 10% and 12%. The majority of patients are treated medically, but complicated dissections, which represent 15% to 20% of cases, require surgical or thoracic endovascular aortic repair (TEVAR). For the best outcomes adequate blood transfusion support is required. Interest in the relationship between blood type and vascular disease has been established. The aim of our study is to evaluate distribution of blood groups among patients with acute aortic type III dissection and to identify any kind of relationship between blood type and patient's survival. From January 2005 to December 2014, 115 patients with acute aortic type III dissection were enrolled at the Clinic of Vascular and Endovascular Surgery in Belgrade, Serbia and retrospectively analyzed. Patients were separated into two groups. The examination group consisted of patients with a lethal outcome, and the control group consisted of patients who survived. The analysis of the blood groups and RhD typing between groups did not reveal a statistically significant difference ( p = 0.220). Our results indicated no difference between different blood groups and RhD typing with respect to in-hospital mortality of patients with acute aortic dissection type III.

  14. Self-perception of aging and acute medical events in chronically institutionalized middle-aged and older persons with schizophrenia.

    PubMed

    Cheng, Sheung-Tak; Yip, Leona C Y; Jim, Olivia T T; Hui, Anna N N

    2012-09-01

    To examine the relationship between self-perceptions of aging and acute medical events in chronically institutionalized middle-aged and older persons with schizophrenia. Participants were 83 persons with schizophrenia (30% women; mean age = 58.48, SD = 8.14) residing in a long-stay care home, who were without organic mental disorders, mental retardation, serious audiovisual impairment, and serious cognitive and physical impairment. They received assessments in body mass index, functional health, and global mental status, and responded to measures of self-perception of aging at baseline. Acute events that required medical attention were recorded for the next 3 months. 8% of the participants had acute medical events. Bivariate analysis suggested that number of comorbid medical conditions, mobility, Mini-Mental State Examination, and negative self-perception of aging were predictive of acute medical events. However, multivariate analysis (logistic regression) showed that only mobility (OR = 0.78, p = 0.04) and negative self-perception of aging (OR = 3.38, p = 0.02) had independent effects on acute medical events, with the latter being the stronger predictor. Positive aging self-perception, body mass index, and smoking were unrelated to medical events. Physical vulnerabilities may not be sufficient to explain the development of acute medical events in late-life schizophrenia. How individuals perceive their aging process, which is expected to regulate health behavior and help-seeking, may be an even more important factor. Further research should investigate whether such self-perceptions, which are probably rooted in stereotypes about aging socialized early in life, are modifiable in this population. Copyright © 2011 John Wiley & Sons, Ltd.

  15. The Heavy Links between Geological Events and Vascular Plants Evolution: A Brief Outline

    PubMed Central

    Piombino, Aldo

    2016-01-01

    Since the rise of photosynthesis, life has influenced terrestrial atmosphere, particularly the O2 and the CO2 content (the latter being originally more than 95%), changing the chemistry of waters, atmosphere, and soils. Billions of years after, a far offspring of these first unicellular forms conquered emerging lands, not only completely changing landscape, but also modifying geological cycles of deposition and erosion, many chemical and physical characteristics of soils and fresh waters, and, more, the cycle of various elements. So, there are no doubts that vascular plants modified geology; but it is true that also geology has affected (and, more, has driven) plant evolution. New software, PyRate, has determined vascular plant origin and diversification through a Bayesian analysis of fossil record from Silurian to today, particularly observing their origination and extinction rate. A comparison between PyRate data and geological history suggests that geological events massively influenced plant evolution and that also the rise of nonflowering seed plants and the fast diffusion of flowering plants can be explained, almost partly, with the environmental condition changes induced by geological phenomena. PMID:26966609

  16. The Heavy Links between Geological Events and Vascular Plants Evolution: A Brief Outline.

    PubMed

    Piombino, Aldo

    2016-01-01

    Since the rise of photosynthesis, life has influenced terrestrial atmosphere, particularly the O2 and the CO2 content (the latter being originally more than 95%), changing the chemistry of waters, atmosphere, and soils. Billions of years after, a far offspring of these first unicellular forms conquered emerging lands, not only completely changing landscape, but also modifying geological cycles of deposition and erosion, many chemical and physical characteristics of soils and fresh waters, and, more, the cycle of various elements. So, there are no doubts that vascular plants modified geology; but it is true that also geology has affected (and, more, has driven) plant evolution. New software, PyRate, has determined vascular plant origin and diversification through a Bayesian analysis of fossil record from Silurian to today, particularly observing their origination and extinction rate. A comparison between PyRate data and geological history suggests that geological events massively influenced plant evolution and that also the rise of nonflowering seed plants and the fast diffusion of flowering plants can be explained, almost partly, with the environmental condition changes induced by geological phenomena.

  17. The Acute Effect of Exercise Intensity on Vascular Function in Adolescents.

    PubMed

    Bond, Bert; Hind, Siobhan; Williams, Craig A; Barker, Alan R

    2015-12-01

    Impairments in vascular function are present in asymptomatic youths with risk factors for cardiovascular disease. Exercise can promote vascular health in youth, but the effects of exercise intensity and the time course in response to acute exercise are unknown. Twenty adolescents (10 male, 14.1 ± 0.3 yr) performed the following on separate days in a counterbalanced order: 1) cycling at 90% of the gas exchange threshold (moderate-intensity exercise (MIE)) and 2) 8 × 1-min cycling at 90% peak power with 75-s recovery (high-intensity interval exercise (HIIE)). The duration of MIE (25.8 ± 2.1 min) was work-matched to HIIE (23.0 min). Macro- and microvascular functions were assessed before, immediately after, and 1 and 2 h after exercise by flow-mediated dilation (FMD) and laser Doppler imaging (total reactive hyperemia). FMD was attenuated immediately after HIIE (P < 0.001, effect size (ES) = 1.20) but not after MIE (P = 0.28, ES = 0.26). Compared with that before exercise, FMD was elevated 1 and 2 h after HIIE (P < 0.001, ES = 1.33; P < 0.001, ES = 1.36) but unchanged in MIE (P = 0.67, ES = 0.10; P = 0.72, ES = 0.08). Changes in FMD were unrelated to shear or baseline arterial diameter. Compared with that in preexercise, total reactive hyperemia was always greater after MIE (P < 0.02, ES > 0.60 for all) and HIIE (P < 0.001, ES > 1.18 for all). Total reactive hyperemia was greater in HIIE compared with that in MIE immediately after (P = 0.03, ES = 0.67) and 1 h after (P = 0.01, ES = 0.62) exercise, with a trend to be greater 2 h after (P = 0.06, ES = 0.45). Exercise intensity is positively associated with macro- and microvascular function 1 and 2 h after exercise. Performing HIIE may provide superior vascular benefits than MIE in adolescents.

  18. Interactions between the vascular endothelial growth factor gene polymorphism and life events in susceptibility to major depressive disorder in a Chinese population.

    PubMed

    Han, Dong; Qiao, Zhengxue; Chen, Lu; Qiu, Xiaohui; Fang, Deyu; Yang, Xiuxian; Ma, Jingsong; Chen, Mingqi; Yang, Jiarun; Wang, Lin; Zhu, Xiongzhao; Zhang, Congpei; Yang, Yanjie; Pan, Hui

    2017-08-01

    Recent studies suggest that vascular endothelial growth factor (VEGF) is involved in the development of major depressive disorder. The aim of this study is to investigate the interaction between vascular endothelial growth factor (VEGF) polymorphism (+405G/C, rs2010963) and negative life events in the pathogenesis of major depressive disorder (MDD). DNA genotyping was performed on peripheral blood leukocytes in 274 patients with MDD and 273 age-and sex-matched controls. The frequency and severity of negative life events were assessed by the Life Events Scale (LES). A logistics method was employed to assess the gene-environment interaction (G×E). Differences in rs2010963 genotype distributions were observed between MDD patients and controls. Significant G×E interactions between allelic variation of rs2010963 and negative life events were observed. Individuals carrying the C alleles were susceptible to MDD only when exposed to high-negative life events. These results indicate that interactions between the VEGF rs2010963 polymorphism and environment increases the risk of developing MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Case management reduces global vascular risk after stroke: secondary results from the The preventing recurrent vascular events and neurological worsening through intensive organized case-management randomized controlled trial.

    PubMed

    McAlister, Finlay A; Grover, Steven; Padwal, Raj S; Youngson, Erik; Fradette, Miriam; Thompson, Ann; Buck, Brian; Dean, Naeem; Tsuyuki, Ross T; Shuaib, Ashfaq; Majumdar, Sumit R

    2014-12-01

    Survivors of ischemic stroke/transient ischemic attack (TIA) are at high risk for other vascular events. We evaluated the impact of 2 types of case management (hard touch with pharmacist or soft touch with nurse) added to usual care on global vascular risk. This is a prespecified secondary analysis of a 6-month trial conducted in outpatients with recent stroke/TIA who received usual care and were randomized to additional monthly visits with either nurse case managers (who counseled patients, monitored risk factors, and communicated results to primary care physicians) or pharmacist case managers (who were also able to independently prescribe according to treatment algorithms). The Framingham Risk Score [FRS]) and the Cardiovascular Disease Life Expectancy Model (CDLEM) were used to estimate 10-year risk of any vascular event at baseline, 6 months (trial conclusion), and 12 months (6 months after last trial visit). Mean age of the 275 evaluable patients was 67.6 years. Both study arms were well balanced at baseline and exhibited reductions in absolute global vascular risk estimates at 6 months: median 4.8% (Interquartile range (IQR) 0.3%-11.3%) for the pharmacist arm versus 5.1% (IQR 1.9%-12.5%) for the nurse arm on the FRS (P = .44 between arms) and median 10.0% (0.1%-31.6%) versus 12.5% (2.1%-30.5%) on the CDLEM (P = .37). These reductions persisted at 12 months: median 6.4% (1.2%-11.6%) versus 5.5% (2.0%-12.0%) for the FRS (P = .83) and median 8.4% (0.1%-28.3%) versus 13.1% (1.6%-31.6%) on the CDLEM (P = .20). Case management by nonphysician providers is associated with improved global vascular risk in patients with recent stroke/TIA. Reductions achieved during the active phase of the trial persisted after trial conclusion. Copyright © 2014 Mosby, Inc. All rights reserved.

  20. Allopurinol use and the risk of acute cardiovascular events in patients with gout and diabetes.

    PubMed

    Singh, Jasvinder A; Ramachandaran, Rekha; Yu, Shaohua; Curtis, Jeffrey R

    2017-03-14

    Few studies, if any, have examined cardiovascular outcomes in patients with diabetes and gout. Both diabetes and gout are risk factors for cardiovascular disease. The objective of this study was to examine the effect of allopurinol on the risk of incident acute cardiovascular events in patients with gout and diabetes. We used the 2007-2010 Multi-Payer Claims Database (MPCD) that linked health plan data from national commercial and governmental insurances, representing beneficiaries with United Healthcare, Medicare, or Medicaid coverage. In patients with gout and diabetes, we assessed the current allopurinol use, defined as a new filled prescription for allopurinol, as the main predictor of interest. Our outcome of interest was the occurrence of the first Incident hospitalized myocardial infarction (MI) or stroke (composite acute cardiovascular event), after which observations were censored. We employed multivariable-adjusted Cox proportional hazards models that simultaneously adjusted for patient demographics, cardiovascular risk factors and other medical comorbidities. We calculated hazard ratios [HR] (95% confidence intervals [CI]) for incident composite (MI or stroke) acute cardiovascular events. We performed sensitivity analyses that additionally adjusted for the presence of immune diseases and colchicine use, as potential confounders. There were 2,053,185 person days (5621.3 person years) of current allopurinol use and 1,671,583 person days (4576.5 person years) of prior allopurinol use. There were 158 incident MIs or strokes in current and 151 in prior allopurinol users, respectively. Compared to previous allopurinol users, current allopurinol users had significantly lower adjusted hazard of incident acute cardiovascular events (incident stroke or MI), with an HR of 0.67 (95% CI, 0.53, 0.84). Sensitivity analyses, additionally adjusted for immune diseases or colchicine use, confirmed this association. Current allopurinol use protected against the occurrence

  1. Hypercapnic evaluation of vascular reactivity in healthy aging and acute stroke via functional MRI.

    PubMed

    Raut, Ryan V; Nair, Veena A; Sattin, Justin A; Prabhakaran, Vivek

    2016-01-01

    Functional MRI (fMRI) is well-established for the study of brain function in healthy populations, although its clinical application has proven more challenging. Specifically, cerebrovascular reactivity (CVR), which allows the assessment of the vascular response that serves as the basis for fMRI, has been shown to be reduced in healthy aging as well as in a range of diseases, including chronic stroke. However, the timing of when this occurs relative to the stroke event is unclear. We used a breath-hold fMRI task to evaluate CVR across gray matter in a group of acute stroke patients (< 10 days from stroke; N = 22) to address this question. These estimates were compared with those from both age-matched (N = 22) and younger (N = 22) healthy controls. As expected, young controls had the greatest mean CVR, as indicated by magnitude and extent of fMRI activation; however, stroke patients did not differ from age-matched controls. Moreover, the ipsilesional and contralesional hemispheres of stroke patients did not differ with respect to any of these measures. These findings suggest that fMRI remains a valid tool within the first few days of a stroke, particularly for group fMRI studies in which findings are compared with healthy subjects of similar age. However, given the relatively high variability in CVR observed in our stroke sample, caution is warranted when interpreting fMRI data from individual patients or a small cohort. We conclude that a breath-hold task can be a useful addition to functional imaging protocols for stroke patients.

  2. Psoriasis and Cardiovascular Comorbidities: Focusing on Severe Vascular Events, Cardiovascular Risk Factors and Implications for Treatment

    PubMed Central

    Hu, Stephen Chu-Sung; Lan, Cheng-Che E.

    2017-01-01

    Psoriasis is a common and chronic inflammatory disease of the skin. It may impair the physical and psychosocial function of patients and lead to decreased quality of life. Traditionally, psoriasis has been regarded as a disease affecting only the skin and joints. More recently, studies have shown that psoriasis is a systemic inflammatory disorder which can be associated with various comorbidities. In particular, psoriasis is associated with an increased risk of developing severe vascular events such as myocardial infarction and stroke. In addition, the prevalence rates of cardiovascular risk factors are increased, including hypertension, diabetes mellitus, dyslipidemia, obesity, and metabolic syndrome. Consequently, mortality rates have been found to be increased and life expectancy decreased in patients with psoriasis, as compared to the general population. Various studies have also shown that systemic treatments for psoriasis, including methotrexate and tumor necrosis factor-α inhibitors, may significantly decrease cardiovascular risk. Mechanistically, the presence of common inflammatory pathways, secretion of adipokines, insulin resistance, angiogenesis, oxidative stress, microparticles, and hypercoagulability may explain the association between psoriasis and cardiometabolic disorders. In this article, we review the evidence regarding the association between psoriasis and cardiovascular comorbidities, focusing on severe vascular events, cardiovascular risk factors and implications for treatment. PMID:29065479

  3. Vascular reactivity and biomarkers of endothelial function in healthy subjects exposed to acute hypobaric hypoxia.

    PubMed

    Iglesias, Diego; Gómez Rosso, Leonardo; Vainstein, Nora; Meroño, Tomás; Lezón, Christian; Brites, Fernando

    2015-11-01

    The aim of this study was to evaluate the effects of acute hypobaric hypoxia (HH) on vascular reactivity and biochemical markers associated with endothelial function (EF). Ten healthy subjects were exposed to a simulated altitude of 4,000 meters above sea level for 4 hours in a hypobaric chamber. Vascular reactivity was measured by the flow-mediated vasodilatation (FMVD) test. Endothelin-1, high sensitive-C reactive protein (hsCRP), vascular cell adhesion molecule 1, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), paraoxonase and adiponectin levels, and FMVD were evaluated before and after the exposure. Subjects were young (age: 32±6 years), lean [body mass index: 23.9±2.0kg/m(2), waist circumference: 77(IQR: 72-80) cm], and presented normal clinical and biochemical parameters. No significant changes were evidenced in FMVD in response to HH (pre: 0.45 (0.20-0.70) vs. during: 0.50 (0.20-1.22) mm; p=0.594). On the other hand, endothelin-1 (+54%, p<0.05), hsCRP (+37%, p<0.001), IL-6 (+75%, p<0.05), TNF-α (+75%, p<0.05), and adiponectin (-39%, p<0.01) levels were significantly altered post-HH. FMVD was increased in 7 subjects, and it was decreased in 3 individuals during HH exposure. Interestingly, when EF biomarkers were compared between these two subgroups of subjects, only post exposure-adiponectin levels were significantly different (49±5 vs. 38±6μg/ml, respectively, p<0.05). HH exposure had an effect on endothelin-1, adiponectin, hsCRP, IL-6, and TNF-α concentration. However, adiponectin was the only biomarker associated with an altered vascular reactivity. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  4. Alcohol consumption and risk of recurrent cardiovascular events and mortality in patients with clinically manifest vascular disease and diabetes mellitus: the Second Manifestations of ARTerial (SMART) disease study.

    PubMed

    Beulens, J W J; Algra, A; Soedamah-Muthu, S S; Visseren, F L J; Grobbee, D E; van der Graaf, Y

    2010-09-01

    This study investigated the relation between alcohol consumption and specific vascular events and mortality in a high risk population of patients with clinical manifestations of vascular disease and diabetes. Patients with clinically manifest vascular disease or diabetes (n=5447) from the SMART study were followed for cardiovascular events and mortality. Alcohol consumption was assessed with a baseline questionnaire and analysed in relation with coronary heart disease (CHD), amputations, stroke, and all-cause and vascular death. After a follow up of 4.7 years, we documented 363 cases of CHD, 187 cases of stroke, 79 amputations and 641 cases of all-cause death, of which 382 were vascular. In multivariate-adjusted models, alcohol consumption was inversely associated with CHD (p(linear trend)=0.007) and stroke (p(linear trend)=0.051) with respective hazard ratios of 0.39 (95%CI: 0.20-0.76) and 0.67 (0.31-1.46) for consuming 10-20 drinks/week compared with abstainers. We observed significant U-shaped associations between alcohol consumption and amputations (p(quadratic trend)=0.001), all-cause death (p(quadratic trend)=0.001) and vascular death (p(quadratic trend)=0.013). Hazard ratios for consuming 10-20 drinks/week were 0.29 (0.07-1.30) for amputations, 0.40 (0.24-0.69) for all-cause death and 0.34 (0.16-0.71) for vascular death compared with abstainers. Similar associations were observed for red wine consumption only. Moderate alcohol consumption (1-2 drinks/day) is not only associated with a reduced risk of vascular and all-cause death in a high risk patients with clinical manifestations of vascular disease, but also with reduced risks of non-fatal events like CHD, stroke and possibly amputations. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  5. Outcomes of lower extremity bypass performed for acute limb ischemia.

    PubMed

    Baril, Donald T; Patel, Virendra I; Judelson, Dejah R; Goodney, Philip P; McPhee, James T; Hevelone, Nathanael D; Cronenwett, Jack L; Schanzer, Andres

    2013-10-01

    Acute limb ischemia remains one of the most challenging emergencies in vascular surgery. Historically, outcomes following interventions for acute limb ischemia have been associated with high rates of morbidity and mortality. The purpose of this study was to determine contemporary outcomes following lower extremity bypass performed for acute limb ischemia. All patients undergoing infrainguinal lower extremity bypass between 2003 and 2011 within hospitals comprising the Vascular Study Group of New England were identified. Patients were stratified according to whether or not the indication for lower extremity bypass was acute limb ischemia. Primary end points included bypass graft occlusion, major amputation, and mortality at 1 year postoperatively as determined by Kaplan-Meier life table analysis. Multivariable Cox proportional hazards models were constructed to evaluate independent predictors of mortality and major amputation at 1 year. Of 5712 lower extremity bypass procedures, 323 (5.7%) were performed for acute limb ischemia. Patients undergoing lower extremity bypass for acute limb ischemia were similar in age (66 vs 67; P = .084) and sex (68% male vs 69% male; P = .617) compared with chronic ischemia patients, but were less likely to be on aspirin (63% vs 75%; P < .0001) or a statin (55% vs 68%; P < .0001). Patients with acute limb ischemia were more likely to be current smokers (49% vs 39%; P < .0001), to have had a prior ipsilateral bypass (33% vs 24%; P = .004) or a prior ipsilateral percutaneous intervention (41% vs 29%; P = .001). Bypasses performed for acute limb ischemia were longer in duration (270 vs 244 minutes; P = .007), had greater blood loss (363 vs 272 mL; P < .0001), and more commonly utilized prosthetic conduits (41% vs 33%; P = .003). Acute limb ischemia patients experienced increased in-hospital major adverse events (20% vs 12%; P < .0001) including myocardial infarction, congestive heart failure exacerbation, deterioration in renal function

  6. Group A beta-haemolytic streptococcal acute chest event in a child with sickle cell anaemia.

    PubMed

    Suara, R O

    2001-06-01

    Acute chest syndrome is a major cause of death and hospitalisation in children with sickle cell anaemia. It is often initiated by an infection, particularly pneumonia. Microbial agents previously not associated with acute chest syndrome are becoming increasingly important. Group A beta-haemolytic Streptococcus (GABHS) is thought to be an uncommon cause of pneumonia in children with sickle cell anaemia. We report a 15-year-old African-American girl who presented with an acute chest event characterised by fever, cough, chest pain, shortness of breath, right upper abdominal quadrant pain, jaundice and otitis media. Chest radiograph showed multi-lobar pneumonia with left pleural effusion. Group A beta-haemolytic Streptococcus was isolated from culture of pleural and middle ear fluids. She responded to therapy that included antibiotics, exchange blood transfusion, oxygen, thoracotomy chest tube drainage and decortication. In a child with sickle cell anaemia presenting with fever and an acute chest event, pneumonia should be considered and GABHS recognised as a possible aetiological agent. In addition, a chest X-ray should be obtained and antibiotics against agents causing community-acquired pneumonia instituted.

  7. 2011 Vascular Research Initiatives Conference: basic foundations of translational research in vascular disease.

    PubMed

    Ziegler, Kenneth R; Dardik, Alan

    2011-07-01

    The Vascular Research Initiatives Conference (VRIC) is an annual conference organized by the Society for Vascular Surgery (SVS). The 2011 VRIC was held in Chicago (IL, USA) to precede and coincide with the first day of the meeting of the Council on Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) of the American Heart Association. The event is designed to present world class vascular research results, encourage collaboration between vascular surgeons and basic scientists in related disciplines, as well as to stimulate interest in research among aspiring academic vascular surgeons. The 2011 VRIC featured plenary sessions addressing peripheral arterial disease, vascular endothelium and thrombosis, aneurysms, and stem cells and tissue engineering. Recipients of the SVS partner grants with the National Institutes of Health K08 awardees presented their progress reports, and keynote addresses were given by Linda Graham and Frank LoGerfo.

  8. Changes in vascular reactivity induced by acute hyperthyroidism in isolated rat aortae.

    PubMed

    Honda, H; Iwata, T; Mochizuki, T; Kogo, H

    2000-06-01

    Hyperthyroidism was induced by subcutaneous injections of L-thyroxine (T(4)) (500 mg/kg/day) for 3 days in order to study whether adrenergic and muscarinic receptor-mediated vascular responses alter at an early stage of the disease. T(4) treatment was sufficient to induce a significant degree of thyroid weight loss, tachycardia, cardiac hypertrophy, and an elevation in serum T(4) levels. The tension of aortic ring preparations isolated from rats was measured isometrically to investigate the influence of acute hyperthyroidism. The contractions induced by norepinephrine (NE) were significantly suppressed in aortic rings from rats treated with T(4) compared with control rats. N(G)-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide synthase (NOS), significantly enhanced NE-induced contraction in aortic rings from both control and T(4)-treated rats, and the enhancement was greater in rats treated with T(4) than control rats. The relaxations induced by either acetylcholine (ACh) or sodium nitroprusside (SNP) were also significantly enhanced by T(4) treatment. L-NOARG abolished the relaxation induced by ACh in aortic rings from both control and T(4)-treated rats. L-NOARG shifted SNP-induced relaxation curves of aortic rings from those of control rats to the left, but not with rats treated with T(4). T(4) treatment showed no influence on the amount of endothelial NOS (eNOS) protein. These results suggest that vascular responses alter at an early stage of hyperthyroidism and that it may be due to a modification in the NO system which is independent from the amount of eNOS protein.

  9. Disentangling the effect of illness perceptions on health status in people with type 2 diabetes after an acute coronary event.

    PubMed

    Vos, Rimke Cathelijne; Kasteleyn, Marise Jeannine; Heijmans, Monique Johanna; de Leeuw, Elke; Schellevis, François Georges; Rijken, Mieke; Rutten, Guy Emile

    2018-03-02

    Chronically ill patients such as people with type 2 diabetes develop perceptions of their illness, which will influence their coping behaviour. Perceptions are formed once a health threat has been recognised. Many people with type 2 diabetes suffer from multimorbidity, for example the combination with cardiovascular disease. Perceptions of one illness may influence perceptions of the other condition. The aim of the current study was to evaluate the effect of an intervention in type 2 diabetes patients with a first acute coronary event on change in illness perceptions and whether this mediates the intervention effect on health status. The current study is a secondary data analysis of a RCT. Two hundred one participants were randomised (1:1 ratio) to the intervention (n = 101, three home visits) or control group (n = 100). Outcome variables were diabetes and acute coronary event perceptions, assessed with the two separate Brief Illness Perceptions Questionnaires (BIPQs); and health status (Euroqol Visual Analog Scale (EQ-VAS)). The intervention effect was analysed using ANCOVA. Linear regression analyses were used to assess whether illness perceptions mediated the intervention effect on health status. A positive intervention effect was found on the BIPQ diabetes items coherence and treatment control (F = 8.19, p = 0.005; F = 14.01, p < 0.001). No intervention effect was found on the other BIPQ diabetes items consequence, personal control, identity, illness concern and emotional representation. Regarding the acute coronary event, a positive intervention effect on treatment control was found (F = 7.81, p = 0.006). No intervention effect was found on the other items of the acute coronary event BIPQ. Better diabetes coherence was associated with improved health status, whereas perceiving more treatment control was not. The mediating effect of the diabetes perception 'coherence' on health status was not significant. Targeting illness

  10. Acute Response of Circulating Vascular Regulating MicroRNAs during and after High-Intensity and High-Volume Cycling in Children.

    PubMed

    Kilian, Yvonne; Wehmeier, Udo F; Wahl, Patrick; Mester, Joachim; Hilberg, Thomas; Sperlich, Billy

    2016-01-01

    The aim of the present study was to analyze the response of vascular circulating microRNAs (miRNAs; miR-16, miR-21, miR-126) and the VEGF mRNA following an acute bout of HIIT and HVT in children. Twelve healthy competitive young male cyclists (14.4 ± 0.8 years; 57.9 ± 9.4 ml·min(-1)·kg(-1) peak oxygen uptake) performed one session of high intensity 4 × 4 min intervals (HIIT) at 90-95% peak power output (PPO), each interval separated by 3 min of active recovery, and one high volume session (HVT) consisting of a constant load exercise for 90 min at 60% PPO. Capillary blood from the earlobe was collected under resting conditions, during exercise (d1 = 20 min, d2 = 30 min, d3 = 60 min), and 0, 30, 60, 180 min after the exercise to determine miR-16, -21, -126, and VEGF mRNA. HVT significantly increased miR-16 and miR-126 during and after the exercise compared to pre-values, whereas HIIT showed no significant influence on the miRNAs compared to pre-values. VEGF mRNA significantly increased during and after HIIT (d1, 30', 60', 180') and HVT (d3, 0', 60'). RESULTS of the present investigation suggest a volume dependent exercise regulation of vascular regulating miRNAs (miR-16, miR-21, miR-126) in children. In line with previous data, our data show that acute exercise can alter circulating miRNAs profiles that might be used as novel biomarkers to monitor acute and chronic changes due to exercise in various tissues.

  11. The effect of acute microgravity on mechanically-induced membrane damage and membrane-membrane fusion events

    NASA Technical Reports Server (NTRS)

    Clarke, M. S.; Vanderburg, C. R.; Feeback, D. L.; McIntire, L. V. (Principal Investigator)

    2001-01-01

    Although it is unclear how a living cell senses gravitational forces there is no doubt that perturbation of the gravitational environment results in profound alterations in cellular function. In the present study, we have focused our attention on how acute microgravity exposure during parabolic flight affects the skeletal muscle cell plasma membrane (i.e. sarcolemma), with specific reference to a mechanically-reactive signaling mechanism known as mechanically-induced membrane disruption or "wounding". Both membrane rupture and membrane resealing events mediated by membrane-membrane fusion characterize this response. We here present experimental evidence that acute microgravity exposure can inhibit membrane-membrane fusion events essential for the resealing of sarcolemmal wounds in individual human myoblasts. Additional evidence to support this contention comes from experimental studies that demonstrate acute microgravity exposure also inhibits secretagogue-stimulated intracellular vesicle fusion with the plasma membrane in HL-60 cells. Based on our own observations and those of other investigators in a variety of ground-based models of membrane wounding and membrane-membrane fusion, we suggest that the disruption in the membrane resealing process observed during acute microgravity is consistent with a microgravity-induced decrease in membrane order.

  12. The Effect of Acute Microgravity on Mechanically-Induced Membrane Damage and Membrane-Membrane Fusion Events

    NASA Technical Reports Server (NTRS)

    Clarke, Mark, S. F.; Vanderburg, Charles R.; Feedback, Daniel L.

    2001-01-01

    Although it is unclear how a living cell senses gravitational forces there is no doubt that perturbation of the gravitational environment results in profound alterations in cellular function. In the present study, we have focused our attention on how acute microgravity exposure during parabolic flight affects the skeletal muscle cell plasma membrane (i.e. sarcolemma), with specific reference to a mechanically-reactive signaling mechanism known as mechanically-induced membrane disruption or "wounding". This response is characterized by both membrane rupture and membrane resealing events mediated by membrane-membrane fusion. We here present experimental evidence that acute microgravity exposure can inhibit membrane-membrane fusion events essential for the resealing of sarcolemmal wounds in individual human myoblasts. Additional evidence to support this contention comes from experimental studies that demonstrate acute microgravity exposure also inhibits secretagogue-stimulated intracellular vesicle fusion with the plasma membrane in HL-60 cells. Based on our own observations and those of other investigators in a variety of ground-based models of membrane wounding and membrane-membrane fusion, we suggest that the disruption in the membrane resealing process observed during acute microgravity is consistent with a microgravity-induced decrease in membrane order.

  13. Elevated leukocyte count and adverse hospital events in patients with acute coronary syndromes: findings from the Global Registry of Acute Coronary Events (GRACE).

    PubMed

    Furman, Mark I; Gore, Joel M; Anderson, Fredrick A; Budaj, Andrzej; Goodman, Shaun G; Avezum, Avaro; López-Sendón, José; Klein, Werner; Mukherjee, Debabrata; Eagle, Kim A; Dabbous, Omar H; Goldberg, Robert J

    2004-01-01

    To examine the association between elevated leukocyte count and hospital mortality and heart failure in patients enrolled in the multinational, observational Global Registry of Acute Coronary Events (GRACE). Elevated leukocyte count is associated with adverse hospital outcomes in patients presenting with acute myocardial infarction (AMI). The association of this prognostic factor with hospital mortality and heart failure in patients with other acute coronary syndromes (ACS) is unclear. We examined the association between admission leukocyte count and hospital mortality and heart failure in 8269 patients presenting with an ACS. This association was examined separately in patients with ST-segment elevation AMI, non-ST-segment elevation AMI, and unstable angina. Leukocyte count was divided into 4 mutually exclusive groups (Q): Q1 <6000, Q2 = 6000-9999, Q3 = 10,000-11,999, Q4 >12,000. Multiple logistic regression analysis was performed to examine the association between elevated leukocyte count and hospital events while accounting for the simultaneous effect of several potentially confounding variables. Increasing leukocyte count was significantly associated with hospital death (adjusted odds ratio [OR] 2.8, 95% CI 2.1-3.6 for Q4 compared to Q2 [normal range]) and heart failure (OR 2.7, 95% CI 2.2-3.4) for patients presenting with ACS. This association was seen in patients with ST-segment elevation AMI (OR for hospital death 3.2, 95% CI 2.1-4.7; OR for heart failure 2.4, 95% CI 1.8-3.3), non-ST-segment elevation AMI (OR for hospital death 1.9, 95% CI 1.2-3.0; OR for heart failure 1.7, 95% CI 1.1-2.5), or unstable angina (OR for hospital death 2.8, 95% CI 1.4-5.5; OR for heart failure 2.0, 95% CI 0.9-4.4). In men and women of all ages with the spectrum of ACS, initial leukocyte count is an independent predictor of hospital death and the development of heart failure.

  14. Risk factors for acute adverse events during ultrasound-guided central venous cannulation in the emergency department.

    PubMed

    Theodoro, Daniel; Krauss, Missy; Kollef, Marin; Evanoff, Bradley

    2010-10-01

    Ultrasound (US) greatly facilitates cannulation of the internal jugular vein. Despite the ability to visualize the needle and anatomy, adverse events still occur. The authors hypothesized that the technique has limitations among certain patients and clinical scenarios. The purpose of this study was to identify characteristics of adverse events surrounding US-guided central venous cannulation (CVC). The authors assembled a prospective observational cohort of emergency department (ED) patients undergoing consecutive internal jugular CVC with US. The primary outcome of interest was a composite of acute mechanical adverse events including hematoma, arterial cannulation, pneumothorax, and unsuccessful placement. Physicians performing the CVC recorded anatomical site, reason for insertion, and acute complications. The patients with catheters were followed until the catheters were removed based on radiographic evidence or hospital nursing records. ED charts and pharmacy records contributed variables of interest. A self-reported online survey provided physician experience information. Logistic regression was used to calculate the odds of an adverse outcome.   Physicians attempted 289 CVCs on 282 patients. An adverse outcome occurred in 57 attempts (19.7%, 95% confidence interval [CI] = 15.5 to 24.7), the most common being 31 unsuccessful placements (11%, 95% CI = 7.7 to 14.8). Patients with a history of end-stage renal disease (odds ratio [OR] = 3.54, 95% CI = 1.59 to 7.89), and central lines placed by operators with intermediate experience (OR = 2.26, 95% CI = 1.19 to 4.32), were most likely to encounter adverse events. Previously cited predictors such as body mass index (BMI), coagulopathy, and pulmonary hyperinflation were not significant in our final model. Acute adverse events occurred in approximately one-fifth of US-guided internal jugular central line attempts. The study identified both patient (history of end-stage renal disease) and physician (intermediate

  15. [Acute limb ischemia from the general surgeon's point of view. How much knowledge of vascular surgery is necessary?].

    PubMed

    Kopp, R; Weidenhagen, R; Hornung, H; Jauch, K W; Lauterjung, L

    2003-12-01

    The diagnosis of acute peripheral ischemia can be obtained based on clinical presentation, inspection, and palpation of the affected extremity. Unfractionated heparin as a single shot is immediately given followed by continuous infusion when diagnosis is clinically evident and contraindications are excluded. Thromboembolectomy using a Fogarty catheter is immediately performed in patients with evidence of arterial embolization and signs of advanced ischemia (TASC IIb/III) followed by intraoperative angiography. Patients with evidence of arterial thrombosis require urgent angiography followed by thrombectomy and probably subsequent endovascular or surgical interventions and vascular reconstruction. For patients with moderate ischemia (TASC IIa), initial diagnostic angiography is recommended followed by primary thrombectomy with subsequent intraoperative angiography and immediate endovascular or operative treatment of remaining vascular problems. As an alternative therapeutic option initial catheter-guided local thrombolysis can be performed in selected patients with the intention of subsequent limb revascularization or unmasking relevant vessel alterations leading to specific endovascular or surgically performed vascular reconstruction. Possible development of muscle ischemia because of increased compartment pressure should be considered and fasciotomy performed when indicated. Primary amputation of the severely ischemic limb after initial thrombectomy might be recommended in patients with life-threatening organ failure related to muscle necrosis.

  16. Association between vascular access failure and microparticles in hemodialysis patients

    PubMed Central

    Ryu, Jung-Hwa; Lim, Su-Young; Ryu, Dong-Ryeol; Kang, Duk-Hee; Choi, Kyu Bok; Kim, Seung-Jung

    2012-01-01

    Background Vascular access failure, a major cause of morbidity in hemodialysis (HD) patients, occurs mainly at stenotic endothelium following an acute thrombotic event. Microparticles (MPs) are fragments derived from injured cell membrane and are closely associated with coagulation and vascular inflammatory responses. Methods We investigated the relationship between levels of circulating MPs and vascular access patency in HD patients. A total of 82 HD patients and 28 healthy patients were enrolled. We used flow cytometry to measure endothelial MPs (EMPs) identified by CD31+CD42− or CD51+ and platelet-derived MPs (PMPs) identified by CD31+CD42+ in plasma samples of participants. Vascular access patency was defined as an interval from the time of access formation to the time of first access stenosis in each patient. MP counts were compared according to access patent duration. Results The levels of EMP (both CD31+CD42− and CD51+) and CD31+CD42+PMP were significantly higher in patients than in healthy participants. Levels of CD31+CD42−EMP and CD31+CD42+PMP showed a positive correlation. In non-diabetic HD patients, CD31+CD42−EMPs and CD31+CD42+PMPs were more elevated in the shorter access survival group (access survival <1 year) than in the longer survival group (access survival ≥ 4 years). Conclusion Elevated circulating EMP or PMP counts are influenced by end-stage renal disease and increased levels of EMP and PMP may be associated with vascular access failure in HD patients. PMID:26889407

  17. Nitrogen Accumulation and Partitioning in High Arctic Tundra from Extreme Atmospheric N Deposition Events

    NASA Astrophysics Data System (ADS)

    Phoenix, G. K.; Osborn, A.; Blaud, A.; Press, M. C.; Choudhary, S.

    2013-12-01

    Arctic ecosystems are threatened by pollution from extreme atmospheric nitrogen (N) deposition events. These events occur from the long-range transport of reactive N from pollution sources at lower latitudes and can deposit up to 80% of the annual N deposition in just a few days. To date, the fate and impacts of these extreme pollutant events has remained unknown. Using a field simulation study, we undertook the first assessment of the fate of acutely deposited N on arctic tundra. Extreme N deposition events were simulated on field plots at Ny-Ålesund, Svalbard (79oN) at rates of 0, 0.04, 0.4 and 1.2 g N m-2 yr-1 applied as NH4NO3 solution over 4 days, with 15N tracers used in the second year to quantify the fate of the deposited N in the plant, soil, microbial and leachate pools. Separate applications of 15NO3- and 15NH4+ were also made to determine the importance of N form in the fate of N. Recovery of the 15N tracer at the end of the first growing season approached 100% of the 15N applied irrespective of treatment level, demonstrating the considerable capacity of High Arctic tundra to capture pollutant N from extreme deposition events. Most incorporation of the 15N was found in bryophytes, followed by the dominant vascular plant (Salix polaris) and the microbial biomass of the soil organic layer. Total recovery remained high in the second growing season (average of 90%), indicating highly conservative N retention. Between the two N forms, recovery of 15NO3- and 15NH4+ were equal in the non-vascular plants, whereas in the vascular plants (particularly Salix polaris) recovery of 15NO3- was four times higher than of 15NH4+. Overall, these findings show that High Arctic tundra has considerable capacity to capture and retain the pollutant N deposited in acute extreme deposition events. Given they can represent much of the annual N deposition, extreme deposition events may be more important than increased chronic N deposition as a pollution source. Furthermore

  18. Using discrete event computer simulation to improve patient flow in a Ghanaian acute care hospital.

    PubMed

    Best, Allyson M; Dixon, Cinnamon A; Kelton, W David; Lindsell, Christopher J; Ward, Michael J

    2014-08-01

    Crowding and limited resources have increased the strain on acute care facilities and emergency departments worldwide. These problems are particularly prevalent in developing countries. Discrete event simulation is a computer-based tool that can be used to estimate how changes to complex health care delivery systems such as emergency departments will affect operational performance. Using this modality, our objective was to identify operational interventions that could potentially improve patient throughput of one acute care setting in a developing country. We developed a simulation model of acute care at a district level hospital in Ghana to test the effects of resource-neutral (eg, modified staff start times and roles) and resource-additional (eg, increased staff) operational interventions on patient throughput. Previously captured deidentified time-and-motion data from 487 acute care patients were used to develop and test the model. The primary outcome was the modeled effect of interventions on patient length of stay (LOS). The base-case (no change) scenario had a mean LOS of 292 minutes (95% confidence interval [CI], 291-293). In isolation, adding staffing, changing staff roles, and varying shift times did not affect overall patient LOS. Specifically, adding 2 registration workers, history takers, and physicians resulted in a 23.8-minute (95% CI, 22.3-25.3) LOS decrease. However, when shift start times were coordinated with patient arrival patterns, potential mean LOS was decreased by 96 minutes (95% CI, 94-98), and with the simultaneous combination of staff roles (registration and history taking), there was an overall mean LOS reduction of 152 minutes (95% CI, 150-154). Resource-neutral interventions identified through discrete event simulation modeling have the potential to improve acute care throughput in this Ghanaian municipal hospital. Discrete event simulation offers another approach to identifying potentially effective interventions to improve patient

  19. Registry on acute cardiovascular events during endurance running races: the prospective RACE Paris registry.

    PubMed

    Gerardin, Benoît; Collet, Jean-Philippe; Mustafic, Hazrije; Bellemain-Appaix, Anne; Benamer, Hakim; Monsegu, Jacques; Teiger, Emmanuel; Livarek, Bernard; Jaffry, Murielle; Lamhaut, Lionel; Fleischel, Catherine; Aubry, Pierre

    2016-08-21

    Long distance running races are associated with a low risk of life-threatening events much often attributed to hypertrophic cardiomyopathy. However, retrospective analyses of aetiology lack consistency. Incidence and aetiology of life-threatening/fatal events were assessed in long distance races in the prospective Registre des Accidents Cardiaques lors des courses d'Endurance (RACE Paris Registry) from October 2006 to September 2012. Characteristics of life-threatening/fatal events were analysed by interviewing survivors and reviewing medical records including post-mortem data of each case. Seventeen life-threatening events were identified of 511 880 runners of which two were fatal. The vast majority were cardiovascular events (13/17) occurring in experienced male runners [mean (±SD) age 43 ± 10 years], with infrequent cardiovascular risk factors, atypical warning symptoms prior to the race or negative treadmill test when performed. Acute myocardial ischaemia was the predominant aetiology (8 of 13) and led to immediate myocardial revascularization. All cases with initial shockable rhythm survived. There was no difference in event rate according to marathons vs. half-marathons and events were clustered at the end of the race. A meta-analysis of all available studies including the RACE Paris registry (n = 6) demonstrated a low prevalence of life-threatening events (0.75/100 000) and that presentation with non-shockable rhythm [OR = 29.9; 95% CI (4.0-222.5), P = 0.001] or non-ischaemic aetiology [OR = 6.4; 95% CI (1.4-28.8), P = 0.015] were associated with case-fatality. Life-threatening/fatal events during long distance races are rare, most often unpredictable and mainly due to acute myocardial ischaemia. Presentation with non-shockable rhythm and non-ischaemic aetiology are the major determinant of case fatality. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  20. Degree of fusiform dilatation of the proximal descending aorta in type B acute aortic dissection can predict late aortic events.

    PubMed

    Marui, Akira; Mochizuki, Takaaki; Koyama, Tadaaki; Mitsui, Norimasa

    2007-11-01

    Predicting the risk factors for late aortic events in patients with type B acute aortic dissection without complications may help to determine a therapeutic strategy for this disorder. We investigated whether late aortic events in type B acute aortic dissection can be predicted accurately by an index that expresses the degree of fusiform dilatation of the proximal descending aorta during the acute phase; this index can be calculated as follows: (maximum diameter of the proximal descending aorta)/(diameter of the distal aortic arch + diameter of the descending aorta at the pulmonary artery level). Patients with type B acute aortic dissection without complications (n = 141) were retrospectively analyzed to determine the predictors of late aortic events; these include aortic dilatation, rupture, refractory pain, organ ischemia, rapid aortic enlargement, and rapid enlargement of ulcer-like projections. The fusiform index in patients with late aortic events (0.59) was higher than that in patients without late aortic events (0.53, P < .01). Patients with a higher fusiform index exhibited aortic dilatation earlier than those with a lower fusiform index. By multivariate analysis, we conclude that the predominant independent predictors of late aortic events were a maximum aortic diameter of 40 mm or more, a patent false lumen, and a fusiform index of 0.64 or more (hazard ratios, 3.18, 2.64, and 2.73, respectively). The values of actuarial freedom from aortic events for patients with all 3 predictors at 1, 5, and 10 years were 22%, 17%, and 8%, respectively, whereas the values in those without these predictors were 97%, 94%, and 90%, respectively. The degree of fusiform dilatation of the proximal descending aorta, a patent false lumen, and a large aortic diameter can be predominant predictors of late aortic events in patients with type B acute aortic dissection. Patients with these predictors should be recommended to undergo early interventions (surgery or stent

  1. Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease.

    PubMed

    Lincoff, A Michael; Nicholls, Stephen J; Riesmeyer, Jeffrey S; Barter, Philip J; Brewer, H Bryan; Fox, Keith A A; Gibson, C Michael; Granger, Christopher; Menon, Venu; Montalescot, Gilles; Rader, Daniel; Tall, Alan R; McErlean, Ellen; Wolski, Kathy; Ruotolo, Giacomo; Vangerow, Burkhard; Weerakkody, Govinda; Goodman, Shaun G; Conde, Diego; McGuire, Darren K; Nicolau, Jose C; Leiva-Pons, Jose L; Pesant, Yves; Li, Weimin; Kandath, David; Kouz, Simon; Tahirkheli, Naeem; Mason, Denise; Nissen, Steven E

    2017-05-18

    The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of

  2. Vascular dysfunctions following spinal cord injury

    PubMed Central

    Popa, F; Grigorean, VT; Onose, G; Sandu, AM; Popescu, M; Burnei, G; Strambu, V; Sinescu, C

    2010-01-01

    The aim of this article is to analyze the vascular dysfunctions occurring after spinal cord injury (SCI). Vascular dysfunctions are common complications of SCI. Cardiovascular disturbances are the leading causes of morbidity and mortality in both acute and chronic stages of SCI. Neuroanatomy and physiology of autonomic nervous system, sympathetic and parasympathetic, is reviewed. SCI implies disruption of descendent pathways from central centers to spinal sympathetic neurons, originating in intermediolateral nuclei of T1–L2 cord segments. Loss of supraspinal control over sympathetic nervous system results in reduced overall sympathetic activity below the level of injury and unopposed parasympathetic outflow through intact vagal nerve. SCI associates significant vascular dysfunction. Spinal shock occurs during the acute phase following SCI and it is a transitory suspension of function and reflexes below the level of the injury. Neurogenic shock, part of spinal shock, consists of severe arterial hypotension and bradycardia. Autonomic dysreflexia appears during the chronic phase, after spinal shock resolution, and it is a life–threatening syndrome of massive imbalanced reflex sympathetic discharge occurring in patients with SCI above the splanchnic sympathetic outflow (T5–T6). Arterial hypotension with orthostatic hypotension occurs in both acute and chronic phases. The etiology is multifactorial. We described a few factors influencing the orthostatic hypotension occurrence in SCI: sympathetic nervous system dysfunction, low plasma catecholamine levels, rennin–angiotensin–aldosterone activity, peripheral alpha–adrenoceptor hyperresponsiveness, impaired function of baroreceptors, hyponatremia and low plasmatic volume, cardiovascular deconditioning, morphologic changes in sympathetic neurons, plasticity within spinal circuits, and motor deficit leading to loss of skeletal muscle pumping activity. Additional associated cardiovascular concerns in SCI, such as

  3. Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXI. Disease activity, damage accrual, and vascular events in pre- and postmenopausal women.

    PubMed

    Fernández, Mónica; Calvo-Alén, Jaime; Alarcón, Graciela S; Roseman, Jeffrey M; Bastian, Holly M; Fessler, Barri J; McGwin, Gerald; Vilá, Luis M; Sanchez, Martha L; Reveille, John D

    2005-06-01

    To determine the differences in clinical manifestations, disease activity, damage accrual, and medication use in systemic lupus erythematosus (SLE) patients as a function of menopausal status at disease onset. Women with SLE as per the criteria of the American College of Rheumatology, with disease duration of 6 months, and/or oophorectomy, and/or increased follicle-stimulating hormone values for reproductive-age women, and/or treatment with hormone replacement therapy. Patients were divided into premenopausal and postmenopausal categories. Socioeconomic status, cumulative clinical manifestations, disease activity (at study entry or time 0, last visit, and over time), as measured by the Systemic Lupus Activity Measure, and damage accrual, as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (at time 0 and at last visit) were compared between the 2 groups of women. Multivariable models were then examined making adjustments for all possible known confounders. Dependent variables in the models were renal involvement, damage accrual, arterial vascular events, and venous thrombosis. Five hundred eighteen women from the LUMINA cohort were included; 436 (84.2%) were premenopausal and 82 (15.8%) were postmenopausal. Disease onset after menopause was more common among Caucasians. Renal involvement was more common in premenopausal women, whereas vascular arterial events were more frequent in postmenopausal women. All other disease manifestations, as well as disease activity, were comparable between both groups. The presence of damage accrual at time 0 and study end was more frequent in

  4. Vascular aging: Chronic oxidative stress and impairment of redox signaling—consequences for vascular homeostasis and disease

    PubMed Central

    Bachschmid, Markus M.; Schildknecht, Stefan; Matsui, Reiko; Zee, Rebecca; Haeussler, Dagmar; Cohen, Richard A.; Pimental, David; van der Loo, Bernd

    2013-01-01

    Characteristic morphological and molecular alterations such as vessel wall thickening and reduction of nitric oxide occur in the aging vasculature leading to the gradual loss of vascular homeostasis. Consequently, the risk of developing acute and chronic cardiovascular diseases increases with age. Current research of the underlying molecular mechanisms of endothelial function demonstrates a duality of reactive oxygen and nitrogen species in contributing to vascular homeostasis or leading to detrimental effects when formed in excess. Furthermore, changes in function and redox status of vascular smooth muscle cells contribute to age-related vascular remodeling. The age-dependent increase in free radical formation causes deterioration of the nitric oxide signaling cascade, alters and activates prostaglandin metabolism, and promotes novel oxidative posttranslational protein modifications that interfere with vascular and cell signaling pathways. As a result, vascular dysfunction manifests. Compensatory mechanisms are initially activated to cope with age-induced oxidative stress, but become futile, which results in irreversible oxidative modifications of biological macromolecules. These findings support the ‘free radical theory of aging’ but also show that reactive oxygen and nitrogen species are essential signaling molecules, regulating vascular homeostasis. PMID:22380696

  5. Metabolic syndrome and the risk of adverse cardiovascular events after an acute coronary syndrome.

    PubMed

    Cavallari, Ilaria; Cannon, Christopher P; Braunwald, Eugene; Goodrich, Erica L; Im, KyungAh; Lukas, Mary Ann; O'Donoghue, Michelle L

    2018-05-01

    Background The incremental prognostic value of assessing the metabolic syndrome has been disputed. Little is known regarding its prognostic value in patients after an acute coronary syndrome. Design and methods The presence of metabolic syndrome (2005 International Diabetes Federation) was assessed at baseline in SOLID-TIMI 52, a trial of patients within 30 days of acute coronary syndrome (median follow-up 2.5 years). The primary endpoint was major coronary events (coronary heart disease death, myocardial infarction or urgent coronary revascularization). Results At baseline, 61.6% ( n = 7537) of patients met the definition of metabolic syndrome, 34.7% (n = 4247) had diabetes and 29.3% had both ( n = 3584). The presence of metabolic syndrome was associated with increased risk of major coronary events (adjusted hazard ratio (adjHR) 1.29, p < 0.0001) and recurrent myocardial infarction (adjHR 1.30, p < 0.0001). Of the individual components of the definition, only diabetes (adjHR 1.48, p < 0.0001) or impaired fasting glucose (adjHR 1.21, p = 0.002) and hypertension (adjHR 1.46, p < 0.0001) were associated with the risk of major coronary events. In patients without diabetes, metabolic syndrome was numerically but not significantly associated with the risk of major coronary events (adjHR 1.13, p = 0.06). Conversely, diabetes was a strong independent predictor of major coronary events in the absence of metabolic syndrome (adjHR 1.57, p < 0.0001). The presence of both diabetes and metabolic syndrome identified patients at highest risk of adverse outcomes but the incremental value of metabolic syndrome was not significant relative to diabetes alone (adjHR 1.07, p = 0.54). Conclusions After acute coronary syndrome, diabetes is a strong and independent predictor of adverse outcomes. Assessment of the metabolic syndrome provides only marginal incremental value once the presence or absence of diabetes is established.

  6. Role of poly-(ADP-ribose) synthetase in lipopolysaccharide-induced vascular failure and acute lung injury in pigs.

    PubMed

    Albertini, M; Clement, M G; Lafortuna, C L; Caniatti, M; Magder, S; Abdulmalek, K; Hussain, S N

    2000-06-01

    To assess the contribution of poly (adenosine 5'-diphosphate ribose) synthetase (PARS) to the development of bacterial lipopolysaccharide (LPS)-induced acute lung injury and vascular failure in pigs. Four groups of anesthetized, paralyzed, and mechanically ventilated domestic white pigs. Group 1 served as control, whereas Escherichia coli LPS (20 microg/kg/h) was continuously infused in group 2. Group 3 received 20 mg/kg injection of 3-aminobenzamide (a selective inhibitor of PARS activity) 15 minutes before LPS infusion. Only 3-aminobenzamide and not LPS was injected in group 4. All animals were examined for 180 minutes. Systemic and pulmonary hemodynamics and lung mechanics were measured during the experimental period. Lung wet/dry ratio, bronchoalveolar lavage (BAL) protein levels and cell counts and lung nitrotyrosine (footprint of peroxynitrite) immunostaining were also measured in a few animals. LPS infusion evoked a progressive decline in systemic arterial pressure, a small increase in cardiac output, and biphasic elevation of pulmonary arterial pressure. Lung compliance declined progressively, whereas lung and total respiratory resistance rose significantly after LPS infusion. Prominent nitrotyrosine immunostaining was detected around small airways and pulmonary endothelium of LPS-infused animals. No significant changes in lung wet/dry ratio and BAL protein levels and cell counts were produced by LPS infusion. Pretreatment with 3-aminobenzamide did not alter the systemic and pulmonary hemodynamic responses to LPS infusion but eliminated the rise in pulmonary and total respiratory resistance. We concluded that PARS activation plays an important role in the changes of lung mechanics associated with LPS-induced acute lung injury but had no role in vascular failure.

  7. Acute antioxidant supplementation and skeletal muscle vascular conductance in aged rats: role of exercise and fiber type.

    PubMed

    Hirai, Daniel M; Copp, Steven W; Schwagerl, Peter J; Haub, Mark D; Poole, David C; Musch, Timothy I

    2011-04-01

    Age-related increases in oxidative stress contribute to impaired skeletal muscle vascular control. However, recent evidence indicates that antioxidant treatment with tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) attenuates flow-mediated vasodilation in isolated arterioles from the highly oxidative soleus muscle of aged rats. Whether antioxidant treatment with tempol evokes similar responses in vivo at rest and during exercise in senescent individuals and whether this effect varies based on muscle fiber type composition are unknown. We tested the hypothesis that redox modulation via acute systemic tempol administration decreases vascular conductance (VC) primarily in oxidative hindlimb locomotor muscles at rest and during submaximal whole body exercise (treadmill running at 20 m/min, 5% grade) in aged rats. Eighteen old (25-26 mo) male Fischer 344 x Brown Norway rats were assigned to either rest (n = 8) or exercise (n = 10) groups. Regional VC was determined via radiolabeled microspheres before and after intra-arterial administration of tempol (302 μmol/kg). Tempol decreased mean arterial pressure significantly by 9% at rest and 16% during exercise. At rest, similar VC in 26 out of 28 individual hindlimb muscles or muscle parts following tempol administration compared with control resulted in unchanged total hindlimb muscle VC (control: 0.18 ± 0.02; tempol: 0.17 ± 0.05 ml·min(-1)·100 g(-1)·mmHg(-1); P > 0.05). During exercise, all individual hindlimb muscles or muscle parts irrespective of fiber type composition exhibited either an increase or no change in VC with tempol (i.e., ↑11 and ↔17 muscles or muscle parts), such that total hindlimb VC increased by 25% (control: 0.93 ± 0.04; tempol: 1.15 ± 0.09 ml·min(-1)·100 g(-1)·mmHg(-1); P ≤ 0.05). These results demonstrate that acute systemic administration of the antioxidant tempol significantly impacts the control of regional vascular tone in vivo presumably via redox modulation and improves

  8. Anaesthesia for vascular emergencies.

    PubMed

    Ellard, L; Djaiani, G

    2013-01-01

    Patients presenting with vascular emergencies including acute aortic syndrome, ruptured thoracic or abdominal aortic aneurysms, thoracic aortic trauma and acute lower limb ischaemia have a high risk of peri-operative morbidity and mortality. Although anatomical suitability is not universal, endovascular surgery may improve mortality and the results of ongoing randomised controlled trials are awaited. Permissive hypotension pre-operatively should be the standard of care with the systolic blood pressure kept to 50-100 mmHg as long as consciousness is maintained. The benefit of local anaesthesia over general anaesthesia is not definitive and this decision should be tailored for a given patient and circumstance. Cerebrospinal fluid drainage for prevention of paraplegia is often impractical in the emergency setting and is not backed by strong evidence; however, it should be considered postoperatively if symptoms develop. We discuss the pertinent anaesthetic issues when a patient presents with a vascular emergency and the impact that endovascular repair has on anaesthetic management. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

  9. Vascular Access Port Implantation and Serial Blood Sampling in a Gottingen Minipig (Sus scrofa domestica) Model of Acute Radiation Injury

    PubMed Central

    Moroni, Maria; Coolbaugh, Thea V; Mitchell, Jennifer M; Lombardini, Eric; Moccia, Krinon D; Shelton, Larry J; Nagy, Vitaly; Whitnall, Mark H

    2011-01-01

    Threats of nuclear and other radiologic exposures have been increasing, but no countermeasure for acute radiation syndrome has been approved by regulatory authorities. Because of their similarity to humans in regard to physiology and anatomy, we are characterizing Gottingen minipigs as a model to aid the development of radiation countermeasures. Irradiated minipigs exhibit immunosuppression, severe thrombocytopenia, vascular leakage, and acute inflammation. These complications render serial acquisition of blood samples problematic. Vascular access ports (VAP) facilitate serial sampling, but their use often is complicated by infections and fibrin deposition. We demonstrate here the successful use of VAP for multiple blood samplings in irradiated minipigs. Device design and limited postoperative prophylactic antimicrobial therapy before irradiation were key to obtaining serial sampling, reducing swelling, and eliminating infection and skin necrosis at the implantation site. Modifications of previous protocols included the use of polydioxanone sutures instead of silk; eliminating chronic port access; single-use, sterile, antireflux prefilled syringes for flushing; strict aseptic weekly maintenance of the device, and acclimating animals to reduce stress. VAP remained functional in 19 of 20 irradiated animals for as long as 3 mo. The remaining VAP failed due to a small leak in the catheter, leading to clot formation. VAP-related sepsis occurred in 2 minipigs. Blood sampling did not cause detectable stress in nonanesthetized sham-irradiated animals, according to leukograms and clinical signs. PMID:21333166

  10. Acute gouty arthritis complicated with acute ST elevation myocardial infarction is independently associated with short- and long-term adverse non-fatal cardiac events.

    PubMed

    Liu, Kuan-Liang; Lee, Hsin-Fu; Chou, Shing-Hsien; Lin, Yen-Chen; Lin, Chia-Pin; Wang, Chun-Li; Chang, Chi-Jen; Hsu, Lung-An

    2014-01-01

    Large epidemiologic studies have associated gouty arthritis with the risk of coronary heart disease. However, there has been a lack of information regarding the outcomes for patients who have gout attacks during hospitalization for acute myocardial infarction. We reviewed the data of 444 consecutive patients who were admitted to our hospital between 2005 and 2008 due to acute ST elevation myocardial infarction (STEMI). The clinical outcomes were compared between patients with gout attack and those without. Of the 444, 48 patients with acute STEMI developed acute gouty arthritis during hospitalization. The multivariate analysis identified prior history of gout and estimated glomerular filtration rate as independent risk factors of gout attack for patients with acute STEMI (odds ratio (OR) 21.02, 95 % CI 2.96-149.26, p = 0.002; OR 0.92, 95 % CI 0.86-0.99, p = 0.035, respectively). The in-hospital mortality and duration of hospital stay did not differ significantly between the gouty group and the non-gouty group (controls). During a mean follow-up of 49 ± 28 months, all-cause mortality and stroke were similar for both groups. Multivariate Cox regression showed that gout attack was independently associated with short- and long-term adverse non-fatal cardiac events (hazard ratio (HR) 1.88, 95 % CI 1.09-3.24, p = 0.024; HR 1.82, 95 % CI 1.09-3.03, p = 0.022, respectively). Gout attack among patients hospitalized due to acute STEMI was independently associated with short-term and long-term rates of adverse non-fatal cardiac events.

  11. Platelet Vascular Endothelial Growth Factor is a Potential Mediator of Transfusion-Related Acute Lung Injury.

    PubMed

    Maloney, James P; Ambruso, Daniel R; Voelkel, Norbert F; Silliman, Christopher C

    The occurrence of non-hemolytic transfusion reactions is highest with platelet and plasma administration. Some of these reactions are characterized by endothelial leak, especially transfusion related acute lung injury (TRALI). Elevated concentrations of inflammatory mediators secreted by contaminating leukocytes during blood product storage may contribute to such reactions, but platelet-secreted mediators may also contribute. We hypothesized that platelet storage leads to accumulation of the endothelial permeability mediator vascular endothelial growth factor (VEGF), and that intravascular administration of exogenous VEGF leads to extensive binding to its lung receptors. Single donor, leukocyte-reduced apheresis platelet units were sampled over 5 days of storage. VEGF protein content of the centrifuged supernatant was determined by ELISA, and the potential contribution of VEGF from contaminating leukocytes was quantified. Isolated-perfused rat lungs were used to study the uptake of radiolabeled VEGF administered intravascularly, and the effect of unlabeled VEGF on lung leak. There was a time-dependent release of VEGF into the plasma fraction of the platelet concentrates (62 ± 9 pg/ml on day one, 149 ± 23 pg/ml on day 5; mean ± SEM, p<0.01, n=8) and a contribution by contaminating leukocytes was excluded. Exogenous 125I-VEGF bound avidly and specifically to the lung vasculature, and unlabeled VEGF in the lung perfusate caused vascular leak. Rising concentrations of VEGF occur during storage of single donor platelet concentrates due to platelet secretion or disintegration, but not due to leukocyte contamination. Exogenous VEGF at these concentrations rapidly binds to its receptors in the lung vessels. At higher VEGF concentrations, VEGF causes vascular leak in uninjured lungs. These data provide further evidence that VEGF may contribute to the increased lung permeability seen in TRALI associated with platelet products.

  12. Melbourne vascular surgical association audit.

    PubMed

    Beiles, C Barry

    2003-01-01

    The formation of the Melbourne Vascular Surgical Association has led to the establishment of a vascular surgical audit programme that commenced in January 1999. This has allowed establishment of a benchmark for quality assurance in vascular surgery in Australia. A consultative process allowed widespread adoption of the audit across all public hospital vascular units in Melbourne and the two largest regional centres in Victoria. Data were collected at two points during admission: at operation and at discharge. Risk stratification, using logistic regression and risk-adjusted ratios for adverse events was assessed for comparison of outcomes between units for the first 3 years of data collection. There is regular contact with all participants for data feedback and quality control. The standard of vascular surgery across Victoria is consistent, and there has been excellent compliance by all academic vascular units. Private practice data are less complete, and only half of the vascular surgeons have participated. A statewide audit process is feasible and viable. Coordination by the Melbourne Vascular Surgical Association is crucial for its continued success.

  13. Patients with metabolic syndrome exhibit higher platelet activity than those with conventional risk factors for vascular disease.

    PubMed

    Serebruany, Victor L; Malinin, Alex; Ong, Stephen; Atar, Dan

    2008-04-01

    The metabolic syndrome is a matter of ongoing debate with regard to its existence, classification, clinical meaningfulness, and associated risks for vessel occlusion. Considering that persistent platelet activation is a cornerstone for the development of acute vascular events, and that patients with type 2 diabetes consistently exhibit high platelet activity, these characteristics may be critical for distinguishing and triageing specific features of metabolic syndrome among established risk factors for vascular disease. We assessed the platelet activity by conventional aggregation, expression of major surface receptors by flow cytometry, and quantitatively by rapid bedside analyzers in 20 aspirin-naïve patients with documented metabolic syndrome, and compared these with 20 untreated subjects with multiple cardiovascular risk factors. Closure time by the PFA-100 analyzer was significantly (P = 0.002) shorter in patients with metabolic syndrome indicating platelet inhibition under high shear conditions. Ultegra analyzer readings revealed increased fibrinogen binding (P = 0.0003) what in combination with the increased expression of PAC-1 (P = 0.32) strongly suggest activation of platelet glycoprotein IIb/IIIa receptor. Surface expression of CD107a (P = 0.014), and SPAN-12 (P = 0.003) were also higher in patients with metabolic syndrome. In contrast, platelet aggregation induced by collagen or ADP, CD31, CD41, CD42b, CD51/61, CD62p, CD63, CD154, CD165, so as formation of platelet-monocyte aggregates, PAR-1 thrombin receptor, and thrombospondin did not differ between groups. Patients with metabolic syndrome exhibited a higher degree of platelet activation than subjects with conventional risk factors for vascular disease. Conceptually, applying adequate antiplatelet strategies may reduce the risk of acute thrombotic events in these patients. Further prospective studies exploring this notion are encouraged.

  14. Impact of tornadoes on hospital admissions for acute cardiovascular events.

    PubMed

    Silva-Palacios, Federico; Casanegra, Ana Isabel; Shapiro, Alan; Phan, Minh; Hawkins, Beau; Li, Ji; Stoner, Julie; Tafur, Alfonso

    2015-11-01

    There is a paucity of data describing cardiovascular events after tornado outbreaks. We proposed to study the effects of tornadoes on the incidence of cardiovascular events at a tertiary care institution. Hospital admission records from a single center situated in a tornado-prone area three months before and after a 2013 tornado outbreak were abstracted. To control for seasonal variation, we also abstracted data from the same period of the prior year (control). Hospital admissions for cardiovascular events (CVEs) including acute myocardial infarction, stroke and venous thromboembolism (VTE) were summated by zip codes, and compared by time period. There were 22,607 admissions analyzed, of which 6,705 (30%), 7,980 (35%), and 7,922 (35%) were during the pre-tornado, post-tornado, and control time frames, respectively. There were 344 CVE in the controls, 317 CVE in pre-tornado and 364 CVEs in post tornado periods. There was no difference in the prevalence of CVE during the post-tornado season compared with the control (PPR=1.05 95% CI: 0.91 to 1.21, p=0.50) or the pre-tornado season (PPR=0.96, 95% CI: 0.83 to 1.21, p=0.63). In conclusion, tornado outbreaks did not increase the prevalence of cardiovascular events. In contrast to the effect of hurricanes, implementation of a healthcare policy change directed toward the early treatment and prevention of cardiovascular events after tornadoes does not seem warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Impact of tornadoes on hospital admissions for acute cardiovascular events

    PubMed Central

    Silva-Palacios, Federico; Casanegra, Ana Isabel; Shapiro, Alan; Phan, Minh; Hawkins, Beau; Li, Ji; Stoner, Julie; Tafur, Alfonso

    2016-01-01

    Background There is a paucity of data describing cardiovascular events after tornado outbreaks. We proposed to study the effects of tornadoes on the incidence of cardiovascular events at a tertiary care institution. Population and methods Hospital admission records from a single center situated in a tornado-prone area three months before and after a 2013 tornado outbreak were abstracted. To control for seasonal variation, we also abstracted data from the same period of the prior year (control). Hospital admissions for cardiovascular events (CVEs) including acute myocardial infarction, stroke and venous thromboembolism (VTE) were summated by zip codes, and compared by time period. Results There were 22,607 admissions analyzed, of which 6,705 (30%), 7,980 (35%), and 7,922 (35%) were during the pre-tornado, post-tornado, and control time frames, respectively. There were 344 CVE in the controls, 317 CVE in pre-tornado and 364 CVEs in post tornado periods. There was no difference in the prevalence of CVE during the post-tornado season compared with the control (PPR = 1.05 95% CI: 0.91 to 1.21, p = 0.50) or the pre-tornado season (PPR= 0.96, 95% CI: 0.83 to 1.21, p = 0.63). Conclusion In conclusion, tornado outbreaks did not increase the prevalence of cardiovascular events. In contrast to the effect of hurricanes, implementation of a healthcare policy change directed toward the early treatment and prevention of cardiovascular events after tornadoes does not seem warranted. PMID:26388119

  16. Oleic acid induces acute pulmonary injury and inflammation in vivo

    EPA Science Inventory

    Oleic acid (OA) is frequently used as a representative fatty acid, and is found in meat-cooking fumes and biodiesel exhaust. Vascular damage and acute lung injury has been observed with OA vascular infusion in models of acute respiratory distress, but it is not yet established ...

  17. Consistent platelet inhibition during long-term maintenance-dose clopidogrel therapy among 359 compliant outpatients with documented vascular disease.

    PubMed

    Serebruany, Victor L; Malinin, Alex I; Atar, Dan; Hanley, Dan F

    2007-03-01

    Numerous reports have dichotomized responses after clopidogrel therapy using varying definitions and platelet tests in patients immediately after acute vascular events; however, no large study has assessed platelet characteristics in outpatients receiving long-term treatment for more than 30 days with the maintenance dose (75 mg/d) of clopidogrel. The aim of this study was to describe the responses of ex vivo measures of platelet aggregation and activation to long-term clopidogrel therapy in a large population of outpatients after coronary stenting or ischemic stroke. We conducted a secondary post hoc analysis of a data set represented by presumably compliant patients after coronary stenting (n = 237) or a documented ischemic stroke (n = 122) treated with clopidogrel-and-aspirin combination antiplatelet therapy. The mean duration of treatment was 5.8 months (range 1-21 months). Every patient exhibited a significant inhibition of adenosine diphosphate-induced platelet aggregation (mean 52.9%, range 36%-70%) as compared with the preclopidogrel measures. Inhibition of aggregation strongly correlated with a diminished expression of PECAM-1 (platelet/endothelial cell adhesion molecule 1, r = 0.75), glycoprotein IIb/IIIa (r = 0.62), and PAR-1 (protease-activated receptor 1, r = 0.71). None of the patients developed hyporesponsiveness (reduction from the baseline <15%) or profound inhibition (residual platelet activity <10%). In contrast to the wide variability of responses that exists in the acute setting, long-term therapy with clopidogrel leads to consistent and much less variable platelet inhibition. Lack of nonresponse and profound inhibition with clopidogrel allow for the maintenance of a delicate balance between proven efficacy and acceptable bleeding risks for long-term secondary prevention in outpatients after acute vascular events.

  18. Brachial-ankle PWV for predicting clinical outcomes in patients with acute stroke.

    PubMed

    Ahn, Kye Taek; Jeong, Jin-Ok; Jin, Seon-Ah; Kim, Mijoo; Oh, Jin Kyung; Choi, Ung-Lim; Seong, Seok-Woo; Kim, Jun Hyung; Choi, Si Wan; Jeong, Hye Seon; Song, Hee-Jung; Kim, Jei; Seong, In-Whan

    2017-08-01

    Although brachial-ankle pulse wave velocity (baPWV) is well-known for predicting the cardiovascular mortality and morbidity, its anticipated value is not demonstrated well concerning acute stroke. Total 1557 patients with acute stroke who performed baPWV were enrolled. We evaluated the prognostic value of baPWV predicting all-cause death and vascular death in patients with acute stroke Results: Highest quartile of baPWV was ≥23.64 m/s. All-caused deaths (including vascular death; 71) were 109 patients during follow-up periods (median 905 days). Multivariate Cox regression analysis revealed that patients with the highest quartile of baPWV had higher risk for vascular death when they are compared with patients with all other three quartiles of baPWV (Hazard ratio with 95% confidence interval [CI] 1.879 [1.022-3.456], p = .042 for vascular death). High baPWV was a strong prognostic value of vascular death in patients with acute stroke.

  19. Tumour Vascular Shutdown and Cell Death Following Ultrasound-Microbubble Enhanced Radiation Therapy

    PubMed Central

    El Kaffas, Ahmed; Gangeh, Mehrdad J.; Farhat, Golnaz; Tran, William Tyler; Hashim, Amr; Giles, Anoja; Czarnota, Gregory J.

    2018-01-01

    High-dose radiotherapy effects are regulated by acute tumour endothelial cell death followed by rapid tumour cell death instead of canonical DNA break damage. Pre-treatment with ultrasound-stimulated microbubbles (USMB) has enabled higher-dose radiation effects with conventional radiation doses. This study aimed to confirm acute and longitudinal relationships between vascular shutdown and tumour cell death following radiation and USMB in a wild type murine fibrosarcoma model using in vivo imaging. Methods: Tumour xenografts were treated with single radiation doses of 2 or 8 Gy alone, or in combination with low-/high-concentration USMB. Vascular changes and tumour cell death were evaluated at 3, 24 and 72 h following therapy, using high-frequency 3D power Doppler and quantitative ultrasound spectroscopy (QUS) methods, respectively. Staining using in situ end labelling (ISEL) and cluster of differentiation 31 (CD31) of tumour sections were used to assess cell death and vascular distributions, respectively, as gold standard histological methods. Results: Results indicated a decrease in the power Doppler signal of up to 50%, and an increase of more than 5 dBr in cell-death linked QUS parameters at 24 h for tumours treated with combined USMB and radiotherapy. Power Doppler and quantitative ultrasound results were significantly correlated with CD31 and ISEL staining results (p < 0.05), respectively. Moreover, a relationship was found between ultrasound power Doppler and QUS results, as well as between micro-vascular densities (CD31) and the percentage of cell death (ISEL) (R2 0.5-0.9). Conclusions: This study demonstrated, for the first time, the link between acute vascular shutdown and acute tumour cell death using in vivo longitudinal imaging, contributing to the development of theoretical models that incorporate vascular effects in radiation therapy. Overall, this study paves the way for theranostic use of ultrasound in radiation oncology as a diagnostic modality to

  20. The free-radical scavenger, edaravone, augments NO release from vascular cells and platelets after laser-induced, acute endothelial injury in vivo.

    PubMed

    Yamashita, T; Shoge, M; Oda, E; Yamamoto, Y; Giddings, J C; Kashiwagi, S; Suematsu, M; Yamamoto, J

    2006-05-01

    In vitro and in vivo experimental models have demonstrated that vascular endothelial function is significantly impaired as a result of oxidative stress, mediated by the generation of oxygen-derived free radicals in response to chronic or acute inflammation. In particular, super-oxide () at specific concentrations leads to the impairment of nitric oxide (NO) bioactivity, and it is known that NO plays a fundamental role in the maintenance of vascular homeostasis. The relationship between reactive oxygen species (ROS) and NO release in thrombosis-related endothelial damage in the peripheral microvasculature remains unclear, however. The purpose of the present study was to investigate the effect of the free-radical scavenger, edaravone, on NO synthesis and thrombotic potential in arterioles after exposure to laser irradiation. Highly sensitive electrochemical NO microsensors were positioned in femoral arterioles of mice, and the kinetics of NO release were recorded in response to standardized laser irradiation in vivo. In addition, images of NO release from damaged vascular cells were investigated in a similar rat model using the NO-sensitive dye 4,5-diaminofluorescein diacetate (DAF-2DA). Thrombogenesis was assessed in carotid arterioles by continuous video microscopy using image analysis software. Laser irradiation led to NO release from perturbed endothelial cells and from platelet-rich thrombi. Edaravone had no significant effect on NO release in non-laser treated, intact endothelium compared with placebo. In contrast, edaravone demonstrated a dose-dependent effect on NO release and thrombogenicity. At a concentration of 10.5 mg/kg per h, edaravone promoted a 5-fold increase in NO and a reduction in platelet-rich thrombus volume to 58% of the placebo values. Our data provide direct evidence to confirm that acute endothelial damage in peripheral microvessels initially induces NO release and that the free-radical scavenger, edaravone, augments NO synthesis leading to

  1. [Localized purpura revealing vascular prosthetic graft infection].

    PubMed

    Boureau, A S; Lescalie, F; Cassagnau, E; Clairand, R; Connault, J

    2013-07-01

    Prosthetic graft infection after vascular reconstruction is a rare but serious complication. We report a case of infection occurring late after implantation of an iliofemoral prosthetic vascular graft. The Staphylococcus aureus infection was revealed by vascular purpura localized on the right leg 7 years after implantation of a vascular prosthesis. This case illustrates an uncommonly late clinical manifestation presenting as an acute infection 7 years after the primary operation. In this situation, the presentation differs from early infection, which generally occurs within the first four postoperative months. Diagnosis and treatment remain a difficult challenge because prosthetic graft infection is a potentially life-threatening complication. Morbidity and mortality rates are high. Here we detail specific aspects of the clinical and radiological presentation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  2. Acute Coronary Syndrome in Indian Subcontinent Patients Residing in the Middle East: Results From Gulf Registry of Acute Coronary Events II.

    PubMed

    Panduranga, Prashanth; Sulaiman, Kadhim J; Al-Zakwani, Ibrahim; Alhabib, Khalid F; Hersi, Ahmad; Suwaidi, Jassim Al; Alsheikh-Ali, Alawi A; Almahmeed, Wael; Saif, Shukri Al; Al-Faleh, Hussam; Al-Lawati, Jawad; Asaad, Nidal; Al-Motarreb, Ahmed; Amin, Haitham

    2015-10-01

    We compared baseline characteristics, clinical presentation, and in-hospital outcomes between Middle Eastern Arabs and Indian subcontinent patients presenting with acute coronary syndrome (ACS). Of the 7930 patients enrolled in Gulf Registry of Acute Coronary Events II (RACE II), 23% (n = 1669) were from the Indian subcontinent. The Indian subcontinent patients, in comparison with the Middle Eastern Arabs, were younger (49 vs 60 years; P < .001), more were males (96% vs 80%; P < .001), had lower proportion of higher Global Registry of Acute Coronary Events risk score (8% vs 27%; P < .001), and less likely to be associated with diabetes (34% vs 42%; P < .001), hypertension (36% vs 51%; P < .001), and hyperlipidemia (29% vs 39%; P < .001) but more likely to be smokers (55% vs 29%; P < .001). After multivariable adjustment, the Middle Eastern Arabs were less likely to be associated with in-hospital congestive heart failure (odds ratio [OR], 0.65; 95% confidence interval [CI]: 0.50-0.86; P = .003) but more likely to be associated with recurrent ischemia (OR 1.33; 95% CI: 1.03-1.71; P = .026) when compared to the Indian subcontinent patients. Despite the baseline differences, there were largely no significant differences in in-hospital outcomes between the Indians and the Middle Eastern Arabs. © The Author(s) 2014.

  3. [Orbito-palpebral vascular pathology].

    PubMed

    Heran Dreyfus, F; Galatoire, O; Koskas, P; Lafitte, F; Nau, E; Bergès, O

    2016-11-01

    Orbito-palpebral vascular pathology represents 10% of all the diseases of this area. The lesion may be discovered during a brain CT scan or MRI, or because it causes clinical symptoms such as orbital mass, visual or oculomotor alteration, pain, proptosis, or acute bleeding due to a complication of the lesion (hemorrhage, thrombosis). We present these lesions using an anatomical, clinical, imaging and therapeutic approach. We distinguish four different entities. Vascular tumors have common imaging characteristics (hypersignal on T2 sequence, contrast enhancement, abnormal vascularization well depicted with ultrasound and Doppler, and possible bleeding). The main lesions are cavernous hemangiomas, the most frequent lesion of that type during adulthood; infantile hemangiomas, the most frequent vascular tumor in children; and more seldomly, hemangioperitcytomas. True vascular malformations are divided according to their flow. Low flow lesions are venous (orbital varix), capillarovenous or lymphatic (lymphangioma). High flow malformations, more rare, are either arteriovenous or arterial malformations (aneurisms). Complex malformations include both low and high flow elements. Lesions leading to modifications of the orbito-palpebral blood flow are mainly due to cavernous sinus abnormalities, either direct carotid-cavernous fistula affecting young adults after severe head trauma, or dural fistula, more insidious, found in older adults. The last section is devoted to congenital syndromic vascular malformations (Sturge-Weber, Rendu-Olser…). This classification allows for a better understanding of these pathologies and their specific imaging features. Copyright © 2016. Published by Elsevier Masson SAS.

  4. The impact of level of education on vascular events and mortality in patients with type 2 diabetes mellitus: Results from the ADVANCE study.

    PubMed

    Blomster, J I; Zoungas, S; Woodward, M; Neal, B; Harrap, S; Poulter, N; Marre, M; Williams, B; Chalmers, J; Hillis, G S

    2017-05-01

    The relationship between educational level and the risk of all-cause mortality is well established, whereas the association with vascular events in individuals with type 2 diabetes is not well described. Any association may reflect a link with common cardiovascular or lifestyle-based risk factors. The relationships between the highest level of educational attainment and major cardiovascular events, microvascular complications and all-cause mortality were explored in a cohort of 11,140 individuals with type 2 diabetes. Completion of formal education before the age of 16 was categorized as a low level of education. Regional differences between Asia, East Europe and Established Market Economies were also assessed. During a median of 5years of follow up, 1031 (9%) patients died, 1147 (10%) experienced a major cardiovascular event and 1136 (10%) a microvascular event. After adjustment for baseline characteristics and risk factors, individuals with lower education had an increased risk of cardiovascular events (hazard ratio (HR) 1.31, 95% CI 1.16-1.48, p<0.0001), microvascular events (HR 1.23, 95% CI 1.08-1.39, p=0.0013) and all-cause mortality (HR 1.34, 95% CI 1.18-1.52, p<0.0001). In regional analyses the increased risk of studied outcomes associated with lower education was weakest in Established Market Economies and strongest in East Europe. A low level of education is associated with an increased risk of vascular events and death in patients with type 2 diabetes, independently of common lifestyle associated cardiovascular risk factors. The effect size varies between geographical regions. Copyright © 2017. Published by Elsevier B.V.

  5. Using the McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey to Predict the Occurrence of Short-Term Coronary Heart Disease Events in Women.

    PubMed

    McSweeney, Jean C; Cleves, Mario A; Fischer, Ellen P; Pettey, Christina M; Beasley, Brittany

    Few instruments capture symptoms that predict cardiac events in the short-term. This study examines the ability of the McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey to predict acute cardiac events within 3 months of administration and to identify the prodromal symptoms most associated with short-term risk in women without known coronary heart disease. The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey was administered to 1,097 women referred to a cardiologist for initial coronary heart disease evaluation. Logistic regression models were used to examine prodromal symptoms individually and in combination to identify the subset of symptoms most predictive of an event within 3 months. Fifty-one women had an early cardiac event. In bivariate analyses, 4 of 30 prodromal symptoms were significantly associated with event occurrence within 90 days. In adjusted analyses, women reporting arm pain or discomfort and unusual fatigue were more likely (OR, 4.67; 95% CI, 2.08-10.48) to have a cardiac event than women reporting neither. The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey may assist in predicting short-term coronary heart disease events in women without known coronary heart disease. Copyright © 2017 Jacobs Institute of Women's Health. All rights reserved.

  6. Characteristic adverse events and their incidence among patients participating in acute ischemic stroke trials.

    PubMed

    Hesse, Kerrick; Fulton, Rachael L; Abdul-Rahim, Azmil H; Lees, Kennedy R

    2014-09-01

    Adverse events (AE) in trial populations present a major burden to researchers and patients, yet most events are unrelated to investigational treatment. We aimed to develop a coherent list of expected AEs, whose incidence can be predicted by patient characteristics that will inform future trials and perhaps general poststroke care. We analyzed raw AE data from patients participating in acute ischemic stroke trials. We identified events that occurred with a lower 99% confidence bound greater than nil. Among these, we applied receiver operating characteristic principles to select the fewest types of events that together represented the greatest number of reports. Using ordinal logistic regression, we modeled the incidence of these events as a function of patient age, sex, baseline National Institutes of Health Stroke Scale, and multimorbidity status, defining P<0.05 as statistically significant. We analyzed 5775 placebo-treated patients, reporting 21 217 AEs. Among 756 types of AEs, 132 accounted for 82.7%, of which 80% began within 10 days after stroke. Right hemisphere (odds ratio [OR], 1.67), increasing baseline National Institutes of Health Stroke Scale (OR, 1.11), multimorbidity status (OR, 1.09 per disease), patient age (OR, 1.01 per year), height (OR, 1.01 per centimeter), diastolic blood pressure (OR, 0.99 per mm Hg), and smoking (OR, 0.82) were independently associated with developing more AEs but together explained only 13% of the variation. A list of 132 expected AEs after acute ischemic stroke may be used to simplify interpretation and reporting of complications. AEs can be modestly predicted by patient characteristics, facilitating stratification of patients by risk for poststroke complications. © 2014 American Heart Association, Inc.

  7. Joint Global War on Terror (GWOT) Vascular Injury Study 2

    DTIC Science & Technology

    2016-02-01

    Iraq. This study proposes to link acute injury and clinical management information from the Joint Theater Trauma Registry (JTTR) to authentic patient...of patient based outcomes following extremity vascular injury in the wars in Afghanistan and Iraq. This study proposes to link acute injury and...deployment, training 3. ACCOMPLISHMENTS: What were the major goals of the project?  Study Phase I ( Acute and Mid-Term Data Collection): o

  8. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial.

    PubMed

    Schwartz, G G; Olsson, A G; Ezekowitz, M D; Ganz, P; Oliver, M F; Waters, D; Zeiher, A; Chaitman, B R; Leslie, S; Stern, T

    2001-04-04

    Patients experience the highest rate of death and recurrent ischemic events during the early period after an acute coronary syndrome, but it is not known whether early initiation of treatment with a statin can reduce the occurrence of these early events. To determine whether treatment with atorvastatin, 80 mg/d, initiated 24 to 96 hours after an acute coronary syndrome, reduces death and nonfatal ischemic events. A randomized, double-blind trial conducted from May 1997 to September 1999, with follow-up through 16 weeks at 122 clinical centers in Europe, North America, South Africa, and Australasia. A total of 3086 adults aged 18 years or older with unstable angina or non-Q-wave acute myocardial infarction. Patients were stratified by center and randomly assigned to receive treatment with atorvastatin (80 mg/d) or matching placebo between 24 and 96 hours after hospital admission. Primary end point event defined as death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization. A primary end point event occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group (relative risk [RR], 0.84; 95% confidence interval [CI], 0.70-1.00; P =.048). There were no significant differences in risk of death, nonfatal myocardial infarction, or cardiac arrest between the atorvastatin group and the placebo group, although the atorvastatin group had a lower risk of symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; RR, 0.74; 95% CI, 0.57-0.95; P =.02). Likewise, there were no significant differences between the atorvastatin group and the placebo group in the incidence of secondary outcomes of coronary revascularization procedures, worsening heart failure, or worsening angina, although there were fewer strokes in the atorvastatin group than in the placebo group (12

  9. Statin adherence and risk of acute cardiovascular events among women: a cohort study accounting for time-dependent confounding affected by previous adherence.

    PubMed

    Lavikainen, Piia; Helin-Salmivaara, Arja; Eerola, Mervi; Fang, Gang; Hartikainen, Juha; Huupponen, Risto; Korhonen, Maarit Jaana

    2016-06-03

    Previous studies on the effect of statin adherence on cardiovascular events in the primary prevention of cardiovascular disease have adjusted for time-dependent confounding, but potentially introduced bias into their estimates as adherence and confounders were measured simultaneously. We aimed to evaluate the effect when accounting for time-dependent confounding affected by previous adherence as well as time sequence between factors. Retrospective cohort study. Finnish healthcare registers. Women aged 45-64 years initiating statin use for primary prevention of cardiovascular disease in 2001-2004 (n=42 807). Acute cardiovascular event defined as a composite of acute coronary syndrome and acute ischaemic stroke was our primary outcome. Low-energy fractures were used as a negative control outcome to evaluate the healthy-adherer effect. During the 3-year follow-up, 474 women experienced the primary outcome event and 557 suffered a low-energy fracture. The causal HR estimated with marginal structural model for acute cardiovascular events for all the women who remained adherent (proportion of days covered ≥80%) to statin therapy during the previous adherence assessment year was 0.78 (95% CI: 0.65 to 0.94) when compared with everybody remaining non-adherent (proportion of days covered <80%). The result was robust against alternative model specifications. Statin adherers had a potentially reduced risk of experiencing low-energy fractures compared with non-adherers (HR 0.90, 95% CI 0.76 to 1.07). Our study, which took into account the time dependence of adherence and confounders, as well as temporal order between these factors, is support for the concept that adherence to statins in women in primary prevention decreases the risk of acute cardiovascular events by about one-fifth in comparison to non-adherence. However, part of the observed effect of statin adherence on acute cardiovascular events may be due to the healthy-adherer effect. Published by the BMJ Publishing

  10. Vascular air embolism

    PubMed Central

    Gordy, Stephanie; Rowell, Susan

    2013-01-01

    Vascular air embolism is a rare but potentially fatal event. It may occur in a variety of procedures and surgeries but is most often associated as an iatrogenic complication of central line catheter insertion. This article reviews the incidence, pathophysiology, diagnosis, treatment, and prevention of this phenomenon. PMID:23724390

  11. Nrf2/Keap1 system regulates vascular smooth muscle cell apoptosis for vascular homeostasis: role in neointimal formation after vascular injury

    PubMed Central

    Ashino, Takashi; Yamamoto, Masayuki; Numazawa, Satoshi

    2016-01-01

    Abnormal increases in vascular smooth muscle cells (VSMCs) in the intimal region after a vascular injury is a key event in developing neointimal hyperplasia. To maintain vascular function, proliferation and apoptosis of VSMCs is tightly controlled during vascular remodeling. NF-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) system, a key component of the oxidative stress response that acts in maintaining homeostasis, plays an important role in neointimal hyperplasia after a vascular injury; however, the role of Nrf2/Keap1 in VSMC apoptosis has not been clarified. Here we report that 14 days after arterial injury in mice, TUNEL-positive VSMCs are detected in both the neointimal and medial layers. These layers contain cells expressing high levels of Nrf2 but low Keap1 expression. In VSMCs, Keap1 depletion induces features of apoptosis, such as positive TUNEL staining and annexin V binding. These changes are associated with an increased expression of nuclear Nrf2. Simultaneous Nrf2 depletion inhibits Keap1 depletion-induced apoptosis. At 14 days after the vascular injury, Nrf2-deficient mice demonstrated fewer TUNEL-positive cells and increased neointimal formation in the neointimal and medial areas. The results suggest that the Nrf2/Keap1 system regulates VSMC apoptosis during neointimal formation, thereby inhibiting neointimal hyperplasia after a vascular injury. PMID:27198574

  12. Effects of acute and chronic exercise in patients with essential hypertension: benefits and risks.

    PubMed

    Gkaliagkousi, Eugenia; Gavriilaki, Eleni; Douma, Stella

    2015-04-01

    The importance of regular physical activity in essential hypertension has been extensively investigated over the last decades and has emerged as a major modifiable factor contributing to optimal blood pressure control. Aerobic exercise exerts its beneficial effects on the cardiovascular system by promoting traditional cardiovascular risk factor regulation, as well as by favorably regulating sympathetic nervous system (SNS) activity, molecular effects, cardiac, and vascular function. Benefits of resistance exercise need further validation. On the other hand, acute exercise is now an established trigger of acute cardiac events. A number of possible pathophysiological links have been proposed, including SNS, vascular function, coagulation, fibrinolysis, and platelet function. In order to fully interpret this knowledge into clinical practice, we need to better understand the role of exercise intensity and duration in this pathophysiological cascade and in special populations. Further studies in hypertensive patients are also warranted in order to clarify the possibly favorable effect of antihypertensive treatment on exercise-induced effects. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Approximate entropy analysis of event-related potentials in patients with early vascular dementia.

    PubMed

    Xu, Jin; Sheng, Hengsong; Lou, Wutao; Zhao, Songzhen

    2012-06-01

    This study investigated differences in event-related potential (ERP) parameters among early vascular dementia (VD) patients, healthy elder controls (ECs), and young controls (YCs). A visual "oddball" color identification task was performed while individuals' electroencephalograms (EEGs) were recorded. Approximate entropy (ApEn), a nonlinear measure, along with P300 latencies and amplitudes were used to analyze ERP data and compare these three groups. The patients with VD showed more complex ERP waveforms and higher ApEn values than did ECs while performing the visual task. It was further found that patients with VD showed reduced P300 amplitudes and increased latencies. The results indicate that patients with VD have fewer attention resources to devote to processing stimuli, lower speed of stimulus classification, and lower synchrony in their cortical activity during the response period. We suggest that ApEn, as a measure of ERP complexity, is a promising marker for early diagnosis of VD.

  14. Salmonella Typhimurium gastroenteritis leading to chronic prosthetic vascular graft infection.

    PubMed

    Cullinan, Milo; Clarke, Michael; Dallman, Tim; Peart, Steven; Wilson, Deborah; Weiand, Daniel

    2017-08-01

    Introduction. It is estimated up to 6 % of prosthetic vascular grafts become infected. Staphylococcus aureus is predominant in early infection and coagulase-negative staphylococci are predominant in late infections. Enterobacteriaceae cause 14-40 % of prosthetic vascular graft infections. This is, to our knowledge the first reported case of Salmonella gastroenteritis causing chronic prosthetic vascular graft infection (PVGI). Case presentation. A 57 years old lady presented with signs and symptoms of prosthetic vascular graft infection. Three years earlier, she had undergone a prosthetic axillo-femoral bypass graft for critical limb ischaemia. The infected prosthetic vascular graft was removed and Salmonella Typhimurium was isolated on culture. In the intervening period, Salmonella Typhimurium was isolated from a faecal specimen, collected during an episode of acute gastroenteritis. Whole-genome sequencing (WGS) showed that the respective Salmonella Typhimurium isolates differed by only a single nucleotide polymorphism (SNP). Salmonella Typhimurium was not isolated on culture of a faecal specimen collected five days following cessation of antimicrobial therapy. Six months after removal of the prosthetic graft, the patient remains under follow-up for her peripheral vascular disease, which currently requires no further surgical intervention. Conclusion. This case has clear implications for the management of chronic PVGI. It is vital to collect high-quality surgical specimens for microbiological analysis and empirical choices of antibiotics are unlikely to cover all potential pathogens. It may also be prudent to enquire about a history of acute gastroenteritis when assessing patients presenting with chronic PVGI.

  15. Systemic Multiple Aneurysms Caused by Vascular Ehlers-Danlos Syndrome.

    PubMed

    Gui, Xinyu; Li, Fangda; Wu, Lingeer; Zheng, Yuehong

    2016-07-01

    Systemic multiple aneurysms are rare and usually associated with collagen tissue disease, such as Ehlers-Danlos syndrome (EDS) or Marfan syndrome. In the present case, we describe a 39-year-old male patient with systemic multiple aneurysms and acute intraperitoneal hemorrhage who was clinically diagnosed with vascular EDS. Coil embolization of the distal segment of the common hepatic artery was performed, which resolved the patient's symptoms. With this case presentation, we aim to increase the awareness of vascular EDS among clinicians and emphasize the extreme fragility of the arteries in patients with vascular EDS. © The Author(s) 2016.

  16. Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke.

    PubMed

    Chiva-Blanch, Gemma; Suades, Rosa; Crespo, Javier; Peña, Esther; Padró, Teresa; Jiménez-Xarrié, Elena; Martí-Fàbregas, Joan; Badimon, Lina

    2016-01-01

    Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke. Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3-7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells) were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls. Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions. Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger cerebral lesions

  17. A randomised trial to investigate the effects of acute consumption of a blackcurrant juice drink on markers of vascular reactivity and bioavailability of anthocyanins in human subjects.

    PubMed

    Jin, Y; Alimbetov, D; George, T; Gordon, M H; Lovegrove, J A

    2011-07-01

    To study the bioavailability of anthocyanins and the effects of a 20% blackcurrant juice drink on vascular reactivity, plasma antioxidant status and other cardiovascular disease risk markers. The study was a randomised, cross-over, double-blind, placebo-controlled acute meal study. Twenty healthy volunteers (11 females and 9 males) were recruited, and all subjects completed the study. Fasted volunteers consumed a 20% blackcurrant juice drink (250 ml) or a control drink following a low-flavonoid diet for the previous 72 h. Vascular reactivity was assessed at baseline and 120 min after juice consumption by laser Doppler imaging (LDI). Plasma and urine samples were collected periodically over an 8-h period for analysis, with a final urine sample collected at 24 h. The cross-over was performed after a 4-week washout. There were no significant effects of the 20% blackcurrant juice drink on acute measures of vascular reactivity, biomarkers of endothelial function or lipid risk factors. Consumption of the test juice caused increases in plasma vitamin C (P=0.006), and urinary anthocyanins (P<0.001). Delphinidin-3-rutinoside and cyanidin-3-rutinoside were the main anthocyanins excreted in urine with delphinidin-3-glucoside also detected. The yield of anthocyanins in urine was 0.021±0.003% of the dietary intake of delphinidin glycosides and 0.009±0.002% of the dietary intake of cyanidin glycosides. The juice consumption did not have a significant effect on vascular reactivity. Anthocyanins were present at low concentrations in the urine, and microbial metabolites of flavonoids were detected in plasma after juice consumption.

  18. The Acute Risks of Exercise in Apparently Healthy Adults and Relevance for Prevention of Cardiovascular Events.

    PubMed

    Goodman, Jack M; Burr, Jamie F; Banks, Laura; Thomas, Scott G

    2016-04-01

    Increased physical activity (PA) is associated with improved quality of life and reductions in cardiovascular (CV) morbidity and all-cause mortality in the general population in a dose-response manner. However, PA acutely increases the risk of adverse CV event or sudden cardiac death (SCD) above levels expected at rest. We review the likelihood of adverse CV events related to exercise in apparently healthy adults and strategies for prevention, and contextualize our understanding of the long-term risk reduction conferred from PA. A systematic review of the literature was performed using electronic databases; additional hand-picked relevant articles from reference lists and additional sources were included after the search. The incidence of adverse CV events in adults is extremely low during and immediately after PA of varying types and intensities and is significantly lower in those with long-standing PA experience. The risk of SCD and nonfatal events during and immediately after PA remains extremely low (well below 0.01 per 10,000 participant hours); increasing age and PA intensity are associated with greater risk. In most cases of exercise-related SCD, occult CV disease is present and SCD is typically the first clinical event. Exercise acutely increases the risk of adverse CV events, with greater risk associated with vigorous intensity. The risks of an adverse CV event during and immediately after exercise are outweighed by the health benefits of vigorous exercise performed regularly. A key challenge remains the identification of occult structural heart disease and inheritable conditions that increase the chances of lethal arrhythmias during exercise. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  19. Long-term evaluation of cardiac and vascular toxicity in patients with Philadelphia chromosome-positive leukemias treated with bosutinib.

    PubMed

    Cortes, Jorge E; Jean Khoury, H; Kantarjian, Hagop; Brümmendorf, Tim H; Mauro, Michael J; Matczak, Ewa; Pavlov, Dmitri; Aguiar, Jean M; Fly, Kolette D; Dimitrov, Svetoslav; Leip, Eric; Shapiro, Mark; Lipton, Jeff H; Durand, Jean-Bernard; Gambacorti-Passerini, Carlo

    2016-06-01

    Vascular and cardiac safety during tyrosine kinase inhibitor (TKI) therapy is an emerging issue. We evaluated vascular/cardiac toxicities associated with long-term bosutinib treatment for Philadelphia chromosome-positive (Ph+) leukemia based on treatment-emergent adverse events (TEAEs) and changes in QTc intervals and ejection fraction in two studies: a phase 1/2 study of second-/third-/fourth-line bosutinib for Ph+ leukemia resistant/intolerant to prior TKIs (N = 570) and a phase 3 study of first-line bosutinib (n = 248) versus imatinib (n = 251) in chronic phase chronic myeloid leukemia. Follow-up time was ≥48 months (both studies). Incidences of vascular/cardiac TEAEs in bosutinib-treated patients were 7%/10% overall with similar incidences observed with first-line bosutinib (5%/8%) and imatinib (4%/6%). Few patients had grade ≥3 vascular/cardiac events (4%/4%) and no individual TEAE occurred in >2% of bosutinib patients. Exposure-adjusted vascular/cardiac TEAE rates (patients with events/patient-year) were low for second-line or later bosutinib (0.037/0.050) and not significantly different between first-line bosutinib (0.015/0.024) and imatinib (0.011/0.017; P ≥ 0.267). Vascular/cardiac events were managed mainly with concomitant medications (39%/44%), bosutinib treatment interruptions (18%/21%), or dose reductions (4%/8%); discontinuations due to these events were rare (0.7%/1.0%). Based on logistic regression modelling, performance status >0 and history of vascular or cardiac disorders were prognostic of vascular/cardiac events in relapsed/refractory patients; hyperlipidemia/hypercholesterolemia and older age were prognostic of cardiac events. In newly diagnosed patients, older age was prognostic of vascular/cardiac events; history of diabetes was prognostic of vascular events. Incidences of vascular and cardiac events were low with bosutinib in the first-line and relapsed/refractory settings following long-term treatment in patients

  20. Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review.

    PubMed

    Warren-Gash, Charlotte; Smeeth, Liam; Hayward, Andrew C

    2009-10-01

    Cardiac complications of influenza infection, such as myocarditis, are well recognised, but the role of influenza as a trigger of acute myocardial infarction is less clear. We did a systematic review of the evidence that influenza (including influenza-like illness and acute respiratory infection) triggers acute myocardial infarction or cardiovascular death. We examined the effectiveness of influenza vaccines at protecting against cardiac events and did a meta-analysis of data from randomised controlled trials. 42 publications describing 39 studies were identified. Many observational studies in different settings with a range of methods reported consistent associations between influenza and acute myocardial infarction. There was weaker evidence of an association with cardiovascular death. Two small randomised trials assessed the protection provided by influenza vaccine against cardiac events in people with existing cardiovascular disease. Whereas one trial found that influenza vaccination gave significant protection against cardiovascular death, the other trial was inconclusive. A pooled estimate from a random-effects model suggests a protective, though non-significant, effect (relative risk 0.51, 95% CI 0.15-1.76). We believe influenza vaccination should be encouraged wherever indicated, especially in people with existing cardiovascular disease, among whom there is often suboptimum vaccine uptake. Further evidence is needed on the effectiveness of influenza vaccines to reduce the risk of cardiac events in people without established vascular disease.

  1. Noninvasive Ventilatory Correction in Patients With Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

    PubMed

    Tsivgoulis, Georgios; Alexandrov, Andrei V; Katsanos, Aristeidis H; Barlinn, Kristian; Mikulik, Robert; Lambadiari, Vaia; Bonakis, Anastasios; Alexandrov, Anne W

    2017-08-01

    Even though current guidelines suggest that noninvasive ventilatory correction (NIVC) could be considered for acute ischemic stroke patients with obstructive sleep apnea, available evidence is conflicting, with no adequately powered randomized clinical trial being available to date. We conducted a systematic review and meta-analysis of all available literature data evaluating the effect of NIVC on neurological improvement (based on decrease in National Institutes of Health Stroke Scale score), vascular events (recurrent stroke, transient ischemic attack, myocardial infarction and unstable angina), and mortality during the follow-up period. We identified 4 randomized clinical trials and 1 prospectively matched observational cohort, comprising a total of 389 patients (59.8% males, mean age: 64.4 years). The risk of both performance and detection bias was considered high in most of the included randomized clinical trials because of the lack of blinding in participants, personnel and/or outcome assessors. The mean decrease in National Institutes of Health Stroke Scale scores during the first (≤30) days of acute ischemic stroke was found to be greater in NIVC-treated patients in comparison to controls (standardized mean difference, 0.38; 95% confidence interval, 0.11-0.66; P =0.007). However, no significant differences were detected between NIVC-treated acute ischemic stroke patients and controls on both the risk of vascular events (risk ratio, 0.53; 95% confidence interval, 0.25-1.14; P =0.11) and mortality (risk ratio, 0.71; 95% confidence interval, 0.37-1.36; P =0.30). No evidence of heterogeneity ( I 2 =0%; P for Cochran Q>0.50) or publication bias were detected in all analyses. NIVC seems to be associated with greater short-term neurological improvement in acute ischemic stroke patients with obstructive sleep apnea. This finding deserves further investigation within the settings of an adequately powered, sham-control, randomized clinical trial. © 2017 American

  2. Outcomes of lower extremity bypass performed for acute limb ischemia

    PubMed Central

    Baril, Donald T.; Patel, Virendra I.; Judelson, Dejah R.; Goodney, Philip P.; McPhee, James T.; Hevelone, Nathanael D.; Cronenwett, Jack L.; Schanzer, Andres

    2013-01-01

    Objective Acute limb ischemia remains one of the most challenging emergencies in vascular surgery. Historically, outcomes following interventions for acute limb ischemia have been associated with high rates of morbidity and mortality. The purpose of this study was to determine contemporary outcomes following lower extremity bypass performed for acute limb ischemia. Methods All patients undergoing infrainguinal lower extremity bypass between 2003 and 2011 within hospitals comprising the Vascular Study Group of New England were identified. Patients were stratified according to whether or not the indication for lower extremity bypass was acute limb ischemia. Primary end points included bypass graft occlusion, major amputation, and mortality at 1 year postoperatively as determined by Kaplan-Meier life table analysis. Multivariable Cox proportional hazards models were constructed to evaluate independent predictors of mortality and major amputation at 1 year. Results Of 5712 lower extremity bypass procedures, 323 (5.7%) were performed for acute limb ischemia. Patients undergoing lower extremity bypass for acute limb ischemia were similar in age (66 vs 67; P = .084) and sex (68% male vs 69% male; P = .617) compared with chronic ischemia patients, but were less likely to be on aspirin (63% vs 75%; P < .0001) or a statin (55% vs 68%; P < .0001). Patients with acute limb ischemia were more likely to be current smokers (49% vs 39%; P < .0001), to have had a prior ipsilateral bypass (33% vs 24%; P = .004) or a prior ipsilateral percutaneous intervention (41% vs 29%; P = .001). Bypasses performed for acute limb ischemia were longer in duration (270 vs 244 minutes; P = .007), had greater blood loss (363 vs 272 mL; P < .0001), and more commonly utilized prosthetic conduits (41% vs 33%; P = .003). Acute limb ischemia patients experienced increased in-hospital major adverse events (20% vs 12%; P < .0001) including myocardial infarction, congestive heart failure exacerbation

  3. Long-term outcome of vertebral artery origin stenosis in patients with acute ischemic stroke

    PubMed Central

    2013-01-01

    Background Vertebral artery origin (VAO) stenosis is occasionally observed in patients who have acute ischemic stroke. We investigated the long-term outcomes and clinical significance of VAO stenosis in patients with acute ischemic stroke. Methods We performed a prospective observational study using a single stroke center registry to investigate the risk of recurrent stroke and vascular outcomes in patients with acute ischemic stroke and VAO stenosis. To relate the clinical significance of VAO stenosis to the vascular territory of the index stroke, patients were classified into an asymptomatic VAO stenosis group and a symptomatic VAO stenosis group. Results Of the 774 patients who had acute ischemic stroke, 149 (19.3%) of them had more than 50% stenosis of the VAO. During 309 patient-years of follow-up (mean, 2.3 years), there were 7 ischemic strokes, 6 hemorrhagic strokes, and 2 unknown strokes. The annual event rates were 0.97% for posterior circulation ischemic stroke, 4.86% for all stroke, and 6.80% for the composite cardiovascular outcome. The annual event rate for ischemic stroke in the posterior circulation was significantly higher in patients who had symptomatic VAO stenosis than in patients who had asymptomatic stenosis (1.88% vs. 0%, p = 0.046). In a multivariate analysis, the hazard ratio, per one point increase of the Essen Stroke Risk Score (ESRS) for the composite cardiovascular outcome, was 1.46 (95% CI, 1.02-2.08, p = 0.036). Conclusions Long-term outcomes of more than 50% stenosis of the VAO in patients with acute ischemic stroke were generally favorable. Additionally, ESRS was a predictor for the composite cardiovascular outcome. Asymptomatic VAO stenosis may not be a specific risk factor for recurrent ischemic stroke in the posterior circulation. However, VAO stenosis may require more clinical attention as a potential source of recurrent stroke when VAO stenosis is observed in patients who have concurrent ischemic stroke in the posterior

  4. History of vasomotor symptoms, extent of coronary artery disease, and clinical outcomes after acute coronary syndrome in postmenopausal women.

    PubMed

    Ferri, Luca A; Morici, Nuccia; Bassanelli, Giorgio; Franco, Nicoletta; Misuraca, Leonardo; Lenatti, Laura; Jacono, Emilia Lo; Leuzzi, Chiara; Corrada, Elena; Aranzulla, Tiziana C; Colombo, Delia; Cagnacci, Angelo; Prati, Francesco; Savonitto, Stefano

    2018-06-01

    Vasomotor symptoms (VMS) during menopausal transition have been linked to a higher burden of cardiovascular risk factors, subclinical vascular disease, and subsequent vascular events. We aim to investigate the association of VMS with the extent of coronary disease and their prognostic role after an acute coronary syndrome. The Ladies Acute Coronary Syndrome study enrolled consecutive women with an acute coronary syndrome undergoing coronary angiography. A menopause questionnaire was administered during admission. Angiographic data underwent corelab analysis. Six out of 10 enrolling centers participated in 1-year follow-up. Outcome data included the composite endpoint of all-cause mortality, recurrent myocardial infarction, stroke, and rehospitalization for cardiovascular causes within 1 year. Of the 415 women with available angiographic corelab analysis, 373 (90%) had complete 1-year follow-up. Among them, 202 women had had VMS during menopausal transition. These women had the same mean age at menopause as those without VMS (50 years in both groups), but were younger at presentation (median age 71 vs 76 years; P < 0.001), despite a more favorable cardiovascular risk profile (chronic kidney dysfunction 4.5% vs 15.9%; P = 0.001; prior cerebrovascular disease 4.5 vs 12.2%; P = 0.018). Extent of coronary disease at angiography was similar between groups (mean Gensini score 49 vs 51; P = 0.6; mean SYNTAX score 14 vs 16; P = 0.3). Overall cardiovascular events at 1 year did not differ between groups (19% vs 22%; P = 0.5). In postmenopausal women with an acute coronary syndrome, a history of VMS was associated with younger age at presentation, despite a lower vascular disease burden and similar angiographically defined coronary disease as compared with women without VMS. No difference could be found in terms of overall clinical outcomes. These results should be interpreted cautiously as all analyses were unadjusted and did not account for risk

  5. O-Linked β-N-Acetylglucosamine Modification of A20 Enhances the Inhibition of NF-κB (Nuclear Factor-κB) Activation and Elicits Vascular Protection After Acute Endoluminal Arterial Injury.

    PubMed

    Yao, Dan; Xu, Lijuan; Xu, Oufan; Li, Rujun; Chen, Mingxing; Shen, Hui; Zhu, Huajiang; Zhang, Fengyi; Yao, Deshang; Chen, Yiu-Fai; Oparil, Suzanne; Zhang, Zhengang; Gong, Kaizheng

    2018-06-01

    Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked β-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling. However, the specific molecular target for O-GlcNAcylation that is responsible for glucosamine-induced vascular protection remains unclear. In this study, we test the hypothesis that increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation is required for glucosamine-mediated inhibition of inflammation and vascular protection. In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation. Thiamet G treatment did not increase A20 protein expression but did significantly enhance binding to TAX1BP1 (Tax1-binding protein 1), a key regulatory protein for A20 activity. Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity. A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects. In balloon-injured rat carotid arteries, glucosamine treatment markedly inhibited neointimal formation and p65 activation compared with vehicle treatment. Adenoviral delivery of A20 shRNA to the injured arteries dramatically reduced balloon injury-induced A20 expression and inflammatory response compared with scramble shRNA and completely abolished the vascular protection of glucosamine. These results suggest that

  6. Prediction model with metabolic syndrome to predict recurrent vascular events in patients with clinically manifest vascular diseases.

    PubMed

    Wassink, Annemarie M; van der Graaf, Yolanda; Janssen, Kristel J; Cook, Nancy R; Visseren, Frank L

    2012-12-01

    Although the overall average 10-year cardiovascular risk for patients with manifest atherosclerosis is considered to be more than 20%, actual risk for individual patients ranges from much lower to much higher. We investigated whether information on metabolic syndrome (MetS) or its individual components improves cardiovascular risk stratification in these patients. We conducted a prospective cohort study in 3679 patients with clinical manifest atherosclerosis from the Secondary Manifestations of ARTerial disease (SMART) study. Primary outcome was defined as any cardiovascular event (cardiovascular death, ischemic stroke or myocardial infarction). Three pre-specified prediction models were derived, all including information on established MetS components. The association between outcome and predictors was quantified using a Cox proportional hazard analysis. Model performance was assessed using global goodness-of-fit fit (χ(2)), discrimination (C-index) and ability to improve risk stratification. A total of 417 cardiovascular events occurred among 3679 patients with 15,102 person-years of follow-up (median follow-up 3.7 years, range 1.6-6.4 years). Compared to a model with age and gender only, all MetS-based models performed slightly better in terms of global model fit (χ(2)) but not C-index. The Net Reclassification Index associated with the addition of MetS (yes/no), the dichotomous MetS-components or the continuous MetS-components on top of age and gender was 2.1% (p = 0.29), 2.3% (p = 0.31) and 7.5% (p = 0.01), respectively. Prediction models incorporating age, gender and MetS can discriminate between patients with clinical manifest atherosclerosis at the highest vascular risk and those at lower risk. The addition of MetS components to a model with age and gender correctly reclassifies only a small proportion of patients into higher- and lower-risk categories. The clinical utility of a prediction model with MetS is therefore limited.

  7. Sex differences in case fatality before and after admission to hospital after acute cardiac events: analysis of community based coronary heart disease register.

    PubMed Central

    Sonke, G. S.; Beaglehole, R.; Stewart, A. W.; Jackson, R.; Stewart, F. M.

    1996-01-01

    OBJECTIVE: To determine whether the reported higher case fatality in hospital after an acute cardiac event in women can be explained by sex differences in mortality before admission and in baseline risk factors. DESIGN: Analyses of data from a community based coronary heart disease register. SETTING: Auckland region, New Zealand. SUBJECTS: 5106 patients aged 25-64 years with an acute cardiac event leading to coronary death or definite myocardial infarction within 28 days of onset, occurring between 1986 and 1992. MAIN OUTCOME MEASURES: Case fatality before admission, 28 day case fatality for patients in hospital, and total case fatality after an acute cardiac event. RESULTS: Despite a more unfavourable risk profile women tended to have lower case fatality before admission than men (crude odds ratio 0.88; 95% confidence interval 0.77 to 1.02). Adjustment for age, living arrangements, smoking, medical history, and treatment increased the effect of sex (0.72; 0.60 to 0.86). After admission to hospital, women had a higher case fatality than men (1.76; 1.43 to 2.17), but after adjustment for confounders this was reduced to 1.18 (0.89 to 1.58). Total case fatality 28 days after an acute cardiac event showed no significant difference between men and women (0.85; 0.70 to 1.02) CONCLUSIONS: The higher case fatality after an acute cardiac event in women admitted to hospital is largely explained by differences in living status, history, and medical treatment and is balanced by a lower case fatality before admission. PMID:8870571

  8. Analyzing discharge strategies during acute care: a discrete-event simulation study.

    PubMed

    Crawford, Elizabeth A; Parikh, Pratik J; Kong, Nan; Thakar, Charuhas V

    2014-02-01

    We developed a discrete-event simulation model of patient pathway through an acute care hospital that comprises an ED and several inpatient units. The effects of discharge timing on ED waiting and boarding times, ambulance diversions, leave without treatment, and readmissions were explicitly modeled. We then analyzed the impact of 1 static and 2 proactive discharge strategies on these system outcomes. Our analysis indicated that although the 2 proactive discharge strategies significantly reduced ED waiting and boarding times, and several other measures, compared with the static strategy (P < 0.01), the number of readmissions increased substantially. Further analysis indicated that these findings are sensitive to changes in patient arrival rate and conditions for ambulance diversion. Determining the appropriate time to discharge patients not only can affect individual patients' health outcomes, but also can affect various aspects of the hospital. The study improves our understanding of how individual inpatient discharge decisions can be objectively viewed in terms of their impact on other operations, such as ED crowding and readmission, in an acute care hospital.

  9. Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

    PubMed

    Khalil, Raouf A

    2013-12-15

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Estrogen, Vascular Estrogen Receptor and Hormone Therapy in Postmenopausal Vascular Disease

    PubMed Central

    Khalil, Raouf A.

    2013-01-01

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women’s Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject’s age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. PMID:24099797

  11. Specific plasma oxylipins increase the odds of cardiovascular and cerebrovascular events in patients with peripheral artery disease.

    PubMed

    Caligiuri, Stephanie P B; Aukema, Harold M; Ravandi, Amir; Lavallée, Renée; Guzman, Randy; Pierce, Grant N

    2017-08-01

    Oxylipins and fatty acids may be novel therapeutic targets for cardiovascular disease. The objective was to determine if plasma oxylipins or fatty acids can influence the odds of cardiovascular/cerebrovascular events. In 98 patients (25 female, 73 male) with peripheral artery disease, the prevalence of transient ischemic attacks, cerebrovascular accidents, stable angina, and acute coronary syndrome was n = 16, 10, 16, and 24, respectively. Risk factors such as being male, diagnosed hypertension, diabetes mellitus, and hyperlipidemia were not associated with events. Plasma fatty acids and oxylipins were analyzed with gas chromatography and HPLC-MS/MS, respectively. None of 24 fatty acids quantified were associated with events. In contrast, 39 plasma oxylipins were quantified, and 8 were significantly associated with events. These 8 oxylipins are known regulators of vascular tone. For example, every 1 unit increase in Thromboxane B 2 /Prostaglandin F 1 α and every 1 nmol/L increase in plasma 16-hydroxyeicosatetraenoic acid, thromboxane B2, or 11,12-dihydroxyeicosatrienoic acid (DiHETrE) increased the odds of having had ≥2 events versus no event (p < 0.05). The greatest predictor was plasma 8,9-DiHETrE, which increased the odds of acute coronary syndrome by 92-fold. In conclusion, specific oxylipins were highly associated with clinical events and may represent specific biomarkers and (or) therapeutic targets of cardiovascular disease.

  12. Paraoxonase 1 (Q192R) gene polymorphism, coronary heart disease and the risk of a new acute coronary event.

    PubMed

    Martínez-Quintana, Efrén; Rodríguez-González, Fayna; Medina-Gil, José María; Garay-Sánchez, Paloma; Tugores, Antonio

    Paraoxonase 1 (PON1) plays a major role in the oxidation of low density lipoprotein and in the prevention of coronary atherogenesis. In this context, coding region polymorphisms of PON1 gene, responsible for the enzyme activity, has become of interest as a marker for atherogenesis. A study and follow-up was conducted on 529 patients with an acute coronary event in order to assess the association between the PON1 Q192R (rs662;A/G) polymorphism, the type of acute coronary syndrome, cardiovascular risk factors (arterial hypertension, diabetes mellitus, dyslipidaemia, and smoking), the extent and severity of coronary atherosclerosis, and the medium-term clinical follow-up. The QQ genotype was found in 245 (46.3%) patients, with 218 (41.2%) patients showing the QR genotype, and 66 (14.5%) patients had the RR genotype. No significant differences were found between the QQ and QR/RR genotypes as regards the clinical characteristics, the analytical data, and the angiographic variables. Similarly, Kaplan-Meier survival analysis showed no significant differences in presenting with a new acute coronary event (p=0.598), cardiac mortality (p=0.701), stent thrombosis (p=0.508), or stent re-stenosis (p=0.598) between QQ and QR/RR genotypes during the follow-up period (3.3±2.2 years). In patients with an acute coronary syndrome, the PON1 Q192R genotypes did not influence the risk of suffering a new acute coronary event during the medium-term follow-up. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Evaluating bococizumab, a monoclonal antibody to PCSK9, on lipid levels and clinical events in broad patient groups with and without prior cardiovascular events: Rationale and design of the Studies of PCSK9 Inhibition and the Reduction of vascular Events (SPIRE) Lipid Lowering and SPIRE Cardiovascular Outcomes Trials.

    PubMed

    Ridker, Paul M; Amarenco, Pierre; Brunell, Robert; Glynn, Robert J; Jukema, J Wouter; Kastelein, John J P; Koenig, Wolfgang; Nissen, Steven; Revkin, James; Santos, Raul D; Schwartz, Pamela F; Yunis, Carla; Tardif, Jean-Claude

    2016-08-01

    Although statins significantly reduce vascular event rates, residual cholesterol risk remains high in many patient groups, including those with known vascular disease as well as in the setting of high-risk primary prevention. Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), prolongs the half-life of hepatic low-density lipoprotein (LDL) receptors, and reduces circulating atherogenic cholesterol levels. The SPIRE program comprises 6 lipid-lowering studies and 2 cardiovascular outcomes trials, each comparing bococizumab (150 mg subcutaneously every 2 weeks) to matching placebo. The 6 SPIRE lipid-lowering studies include 3 parallel 12-month assessments of bococizumab on atherogenic lipids among statin-treated individuals at high residual risk (SPIRE-HR, SPIRE-LDL, SPIRE-LL), one 12-month study of bococizumab among individuals with familial hypercholesterolemia (SPIRE-FH), one 6-month study of bococizumab among those with statin intolerance (SPIRE-SI), and one 3-month study of bococizumab delivery using an auto-injector device (SPIRE-AI). The SPIRE-1 and SPIRE-2 event-driven cardiovascular outcome trials will assess the efficacy and safety of bococizumab in the prevention of incident vascular events in high-risk populations with and without clinically evident cardiovascular disease who have directly measured entry LDL cholesterol levels ≥70 mg/dL (SPIRE-1, n = 17,000) or ≥100 mg/dL (SPIRE-2, n = 11,000). The SPIRE trials, inclusive of more than 30,000 participants worldwide, will ascertain the magnitude of reduction in atherogenic lipids that accrue with bococizumab and determine whether the addition of this PCSK9 inhibitor to standard treatment significantly reduces cardiovascular morbidity and mortality in high-risk patients, including those without a history of clinical cardiovascular events. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Inflammation markers and prediction of post-stroke vascular disease recurrence: the MITICO study.

    PubMed

    Castillo, J; Alvarez-Sabín, J; Martínez-Vila, E; Montaner, J; Sobrino, T; Vivancos, J

    2009-02-01

    Vascular disease recurrence following stroke is the main cause of morbidity and mortality. The MITICO study was designed to assess the prognostic value of markers of inflammation in relation to the risk of recurrence of vascular disease. Multi-centered prospective observational study, in patients with ischemic stroke not receiving anti-coagulation therapy and who were recruited within 1-3 months from stroke onset. Blood samples were obtained at baseline and follow- up for the determination of high-sensitive C reactive protein (CRP), IL-6, IL-10, ICAM-1, VCAM- 1, MMP-9 and cellular fibronectin. Four follow-up visits within the first year were to rule out recurrence. Of 965 patients from 65 hospitals, 780 (aged 67.5+/-11.2 years, 33.6 % female) were valid for main analysis. One-hundred and three patients (13.2 %) had a new adverse vascular event and 116 patients (14.9 %) a vascular event or vascular death (66.4 % stroke, 21.5 % coronary and 12.1 % peripheral). Levels of IL-6 > 5 pg/mL and VCAM-1 > 1350 ng/mL (ROC curve analyses) were associated with vascular disease recurrence risk (OR: 28.7; 95 % CI: 14.2-58.0 vs. OR: 4.1; 95 % CI: 2.4-7.1, respectively) following adjustment for confounding variables. Risk of adverse vascular event or death from vascular disease were associated with IL-6 (OR: 21.2; 95 % CI: 11.6-38.7) and VCAM-1 (OR: 3.8; 95 % CI: 2.3-6.4). Baseline values of IL-6 > 5 pg/mL and VCAM-1 > 1350 ng/mL increase 21-fold and 4-fold, respectively, the risk of new vascular disease event or death from vascular disease in patients with ischemic stroke not receiving anti-coagulation treatment.

  15. Angiography in the Isolated Perfused Kidney: Radiological Evaluation of Vascular Protection in Tissue Ablation by Nonthermal Irreversible Electroporation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wendler, Johann Jakob, E-mail: johann.wendler@med.ovgu.de; Pech, Maciej; Blaschke, Simon

    2012-04-15

    Purpose: The nonthermal irreversible electroporation (NTIRE) is a novel nonthermal tissue ablation technique by local application of high-voltage current within microseconds leading to a delayed apoptosis. The purpose of this experimental study was the first angiographic evaluation of the acute damage of renal vascular structure in NTIRE. Methods: Results of conventional dynamic digital substraction angiography (DSA) and visualization of the terminal vascular bed of renal parenchyma by high-resolution X-ray in mammography technique were evaluated before, during, and after NTIRE of three isolated perfused porcine ex vivo kidneys. Results: In the dedicated investigation, no acute vascular destruction of the renal parenchymamore » and no dysfunction of the kidney perfusion model were observed during or after NTIRE. Conspicuous were concentric wave-like fluctuations of the DSA contrast agent simultaneous to the NTIRE pulses resulting from NTIRE pulse shock wave. Conclusion: The NTIRE offers an ablation method with no acute collateral vascular damage in angiographic evaluation.« less

  16. Hospital admissions for asthma and acute bronchitis in El Paso, Texas: do age, sex, and insurance status modify the effects of dust and low wind events?

    PubMed

    Grineski, Sara E; Staniswalis, Joan G; Bulathsinhala, Priyangi; Peng, Yanlei; Gill, Thomas E

    2011-11-01

    El Paso County (Texas) is prone to still air inversions and is one of the dust "hot spots" in North America. In this context, we examined the sub-lethal effects of airborne dust and low wind events on human respiratory health (i.e., asthma and acute bronchitis) between 2000 and 2003, when 110 dust and 157 low wind events occurred. Because environmental conditions may not affect everyone the same, we explored the effects of dust and low wind within three age groups (children, adults, and the elderly), testing for effect modifications by sex and insurance status, while controlling for weather and air pollutants. We used a case-crossover design using events matched with referent days on the same day-of-the-week, month, and year with conditional logistic regression to estimate the probability of hospital admission, while controlling for apparent temperature (lag 1), nitrogen dioxide, and particulate matter of 2.5μm or less. Children (aged 1-17) were 1.19 (95% confidence interval: 1.00-1.41) times more likely to be hospitalized for asthma three days after a low wind event, and 1.33 (95% CI: 1.01-1.75) times more likely to be hospitalized for acute bronchitis one day after a dust event than on a clear day. Girls were more sensitive to acute bronchitis hospitalizations after dust events (1.83, 95% CI: 1.09-3.08) than boys, but less sensitive than boys to acute bronchitis hospitalizations after low wind events (0.68, 95% CI: 0.46-1.00). We found general trends with regard to dust and low wind events being associated with increased odds of hospitalization for asthma and bronchitis amongst all ages and adults (aged 18-64). Adults covered by Medicaid and adults without health insurance had higher risks of hospitalization for asthma and acute bronchitis after both low wind and dust events. Results suggest that there were respiratory health effects associated with dust and low wind events in El Paso, with stronger impacts among children and poor adults. Girls and boys with

  17. Hospital admissions for asthma and acute bronchitis in El Paso, Texas: Do age, sex, and insurance status modify the effects of dust and low wind events?

    PubMed Central

    Staniswalis, Joan G.; Bulathsinhala, Priyangi; Peng, Yanlei; Gill, Thomas E.

    2013-01-01

    Background El Paso County (Texas) is prone to still air inversions and is one of the dust “hot spots” in North America. In this context, we examined the sub-lethal effects of airborne dust and low wind events on human respiratory health (i.e., asthma and acute bronchitis) between 2000 and 2003, when 110 dust and 157 low wind events occurred. Because environmental conditions may not affect everyone the same, we explored the effects of dust and low wind within three age groups (children, adults, and the elderly), testing for effect modifications by sex and insurance status, while controlling for weather and air pollutants. Methods We used a case-crossover design using events matched with referent days on the same day-of-the-week, month, and year with conditional logistic regression to estimate the probability of hospital admission, while controlling for apparent temperature (lag 1), nitrogen dioxide, and particulate matter of 2.5 micrometers or less. Results Children (aged 1–17) were 1.19 (95% confidence interval: 1.00–1.41) times more likely to be hospitalized for asthma three days after a low wind event, and 1.33 (95% CI: 1.01–1.75) times more likely to be hospitalized for acute bronchitis one day after a dust event than on a clear day. Girls were more sensitive to acute bronchitis hospitalizations after dust events (1.83, 95% CI: 1.09–3.08) than boys, but less sensitive than boys to acute bronchitis hospitalizations after low wind events (0.68, 95% CI: 0.46–1.00). We found general trends with regard to dust and low wind events being associated with increased odds of hospitalization for asthma and bronchitis amongst all ages and adults (aged 18–64). Adults covered by Medicaid and adults without health insurance had higher risks of hospitalization for asthma and acute bronchitis after both low wind and dust event Conclusions Results suggest that there were respiratory health effects associated with dust and low wind events in El Paso, with stronger

  18. [Use of a new cobetalactamine in the therapy of acute and chronic odontogenic processes].

    PubMed

    De Siate, A

    1979-01-01

    Treatment of 70 patients with acute and chronic odontogenic processes for 5-35 days (mean 10.9 days) with a new cobetalactamine is reported. Rapid resolution was noted in nosological groups marked by the presence of acute infection. Particular interest is attached to the effect of the drug on chronicisting infections, such as apical granuloma, maxillary osteitis, and radicular cysts, since these forms displayed a high degree of vascular isolation, were often sustained by a mixed flora, and had been previously treated with other antibiotics. Follow-up four weeks after the conclusion of treatment showed a low incidence of recurrences that was in all events lower than in earlier experiments with chemical antibiotics. There were no instances of intolerance or allergy.

  19. Src- and Fyn-dependent apical membrane trafficking events control endothelial lumen formation during vascular tube morphogenesis.

    PubMed

    Kim, Dae Joong; Norden, Pieter R; Salvador, Jocelynda; Barry, David M; Bowers, Stephanie L K; Cleaver, Ondine; Davis, George E

    2017-01-01

    Here we examine the question of how endothelial cells (ECs) develop their apical membrane surface domain during lumen and tube formation. We demonstrate marked apical membrane targeting of activated Src kinases to this apical domain during early and late stages of this process. Immunostaining for phosphotyrosine or phospho-Src reveals apical membrane staining in intracellular vacuoles initially. This is then followed by vacuole to vacuole fusion events to generate an apical luminal membrane, which is similarly decorated with activated phospho-Src kinases. Functional blockade of Src kinases completely blocks EC lumen and tube formation, whether this occurs during vasculogenic tube assembly or angiogenic sprouting events. Multiple Src kinases participate in this apical membrane formation process and siRNA suppression of Src, Fyn and Yes, but not Lyn, blocks EC lumen formation. We also demonstrate strong apical targeting of Src-GFP and Fyn-GFP fusion proteins and increasing their expression enhances lumen formation. Finally, we show that Src- and Fyn-associated vacuoles track and fuse along a subapically polarized microtubule cytoskeleton, which is highly acetylated. These vacuoles generate the apical luminal membrane in a stereotypically polarized, perinuclear position. Overall, our study identifies a critical role for Src kinases in creating and decorating the EC apical membrane surface during early and late stages of lumen and tube formation, a central event in the molecular control of vascular morphogenesis.

  20. Nonurgent commercial air travel after acute coronary syndrome: a review of 288 patient events.

    PubMed

    Pearce, Emily; Haffner, Faith; Brady, Lauren B; Sochor, Mark; Duchateau, Francois X; O'Connor, Robert E; Verner, Laurent; Brady, William J

    2014-01-01

    We studied a population of individuals who experienced an acute coronary syndrome (ACS) event while traveling abroad and required nonurgent commercial air travel to the home region. This retrospective study gathered data from 288 patients enrolled in a travel-based medical assistance program. Interventions, complications, and travel home were assessed for trends. Descriptive and comparison statistical analyses were performed. Two hundred eighty-eight patients were identified and entered into the review. Of the patients in this study, 77.1% were male with an average age of 67.7 years. One hundred sixteen (40.3%) patients were diagnosed with unstable angina pectoris (USAP), whereas the remaining 172 (59.7%) patients experienced acute myocardial infarction (AMI). Regarding inpatient complications during the initial admission, 121 (42.0%) patients experienced 1 or more adverse event. The average number of days after an ACS event that a patient began to travel home was 10.5 days for the entire patient population (USAP patients = 8.8 days, AMI patients = 11.8 days). Two hundred twenty (76.4%) patients traveled with a medical escort, and 48 (16.7%) patients received supplemental oxygen during air travel. Four (1.4%) in-flight adverse events occurred in the following ACS diagnostic groups: 2 in the complicated AMI group, 1 in the uncomplicated USAP group, and 1 in the uncomplicated AMI group. No in-flight deaths occurred. Nine (3.1%) deaths were noted within 2 weeks after returning to the home region. The deaths after returning to the home region occurred in the following ACS diagnostic groups: 2 in the complicated USAP group, 1 in the uncomplicated USAP group, and 6 in the complicated AMI group. None of the patients who experienced in-flight events died after returning to their home region. Upon discharge, the vast majority of ACS patients who travel to their home region via commercial air do not experience adverse events in-flight; when such adverse events occur in

  1. Recurrent Ischemic Lesions After Acute Atherothrombotic Stroke: Clopidogrel Plus Aspirin Versus Aspirin Alone.

    PubMed

    Hong, Keun-Sik; Lee, Seung-Hoon; Kim, Eung Gyu; Cho, Ki-Hyun; Chang, Dae Il; Rha, Joung-Ho; Bae, Hee-Joon; Lee, Kyung Bok; Kim, Dong Eog; Park, Jong-Moo; Kim, Hahn-Young; Cha, Jae-Kwan; Yu, Kyung-Ho; Lee, Yong-Seok; Lee, Soo Joo; Choi, Jay Chol; Cho, Yong-Jin; Kwon, Sun U; Kim, Gyeong-Moon; Sohn, Sung-Il; Park, Kwang-Yeol; Kang, Dong-Wha; Sohn, Chul-Ho; Lee, Jun; Yoon, Byung-Woo

    2016-09-01

    In patients with acute ischemic stroke caused by large artery atherosclerosis, clopidogrel plus aspirin versus aspirin alone might be more effective to prevent recurrent cerebral ischemia. However, there is no clear evidence. In this multicenter, double-blind, placebo-controlled trial, we randomized 358 patients with acute ischemic stroke of presumed large artery atherosclerosis origin within 48 hours of onset to clopidogrel (75 mg/d without loading dose) plus aspirin (300-mg loading followed by 100 mg/d) or to aspirin alone (300-mg loading followed by 100 mg/d) for 30 days. The primary outcome was new symptomatic or asymptomatic ischemic lesion on magnetic resonance imaging within 30 days. Secondary outcomes were 30-day functional disability, clinical stroke recurrence, and composite of major vascular events. Safety outcome was any bleeding. Of 358 patients enrolled, 334 (167 in each group) completed follow-up magnetic resonance imaging. The 30-day new ischemic lesion recurrence rate was comparable between the clopidogrel plus aspirin and the aspirin monotherapy groups (36.5% versus 35.9%; relative risk, 1.02; 95% confidence interval, 0.77-1.35; P=0.91). Of the recurrent ischemic lesions, 94.2% were clinically asymptomatic. There were no differences in secondary outcomes between the 2 groups. Any bleeding were more frequent in the combination group than in the aspirin monotherapy group, but the difference was not significant (16.7% versus 10.7%; P=0.11). One hemorrhagic stroke occurred in the clopidogrel plus aspirin group. Clopidogrel plus aspirin might not be superior to aspirin alone for preventing new ischemic lesion and clinical vascular events in patients with acute ischemic stroke caused by large artery atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00814268. © 2016 American Heart Association, Inc.

  2. Dysregulation of Serum Gamma Interferon Levels in Vascular Chronic Q Fever Patients Provides Insights into Disease Pathogenesis

    PubMed Central

    Kremers, Marjolein N. T.; Hodemaekers, Hennie M.; Hagenaars, Julia C. J. P.; Koning, Olivier H. J.; Renders, Nicole H. M.; Hermans, Mirjam H. A.; de Klerk, Arja; Notermans, Daan W.; Wever, Peter C.; Janssen, Riny

    2015-01-01

    A large community outbreak of Q fever occurred in the Netherlands in the period 2007 to 2010. Some of the infected patients developed chronic Q fever, which typically includes pathogen dissemination to predisposed cardiovascular sites, with potentially fatal consequences. To identify the immune mechanisms responsible for ineffective clearance of Coxiella burnetii in patients who developed chronic Q fever, we compared serum concentrations of 47 inflammation-associated markers among patients with acute Q fever, vascular chronic Q fever, and past resolved Q fever. Serum levels of gamma interferon were strongly increased in acute but not in vascular chronic Q fever patients, compared to past resolved Q fever patients. Interleukin-18 levels showed a comparable increase in acute as well as vascular chronic Q fever patients. Additionally, vascular chronic Q fever patients had lower serum levels of gamma interferon-inducible protein 10 (IP-10) and transforming growth factor β (TGF-β) than did acute Q fever patients. Serum responses for these and other markers indicate that type I immune responses to C. burnetii are affected in chronic Q fever patients. This may be attributed to an affected immune system in cardiovascular patients, which enables local C. burnetii replication at affected cardiovascular sites. PMID:25924761

  3. The "Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes": Study protocol.

    PubMed

    Barchetta, I; Capoccia, D; Baroni, M G; Buzzetti, R; Cavallo, M G; De Cosmo, S; Leonetti, F; Leotta, S; Morano, S; Morviducci, L; Prudente, S; Pugliese, G; Trischitta, V

    2016-02-01

    The rate of mortality in diabetic patients, especially of cardiovascular origin, is about twice as much that of nondiabetic individuals. Thus, the pathogenic factors shaping the risk of mortality in such patients must be unraveled in order to target intensive prevention and treatment strategies. The "Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes" is aimed at identifying new molecular promoters of mortality and major vascular events in patients with type 2 diabetes mellitus (T2DM). The "SUMMER study in diabetes" is an observational, prospective, and collaborative study conducted on at least 5000 consecutive patients with T2DM, recruited from several diabetes clinics of Central-Southern Italy and followed up for a minimum of 5 years. The primary outcome is all-cause mortality; the secondary outcomes are cardiovascular mortality, acute myocardial infarction, stroke, and dialysis. A biobank will be created for genomic, transcriptomic, and metabolomic analysis, in order to unravel new molecular predictors of mortality and vascular morbidity. The "SUMMER study in diabetes" is aimed at identifying new molecular promoters of mortality and major vascular events in patients with T2DM. These novel pathogenic factors will most likely be instrumental in unraveling new pathways underlying such dramatic events. In addition, they will also be used as additional markers to increase the performance of the already existing risk-scoring models for predicting the above-mentioned outcomes in T2DM, as well as for setting up new preventive and treatment strategies, possibly tailored to specific pathogenic backgrounds. ClinicalTrials.gov, NCT02311244; URL https://clinicaltrials.gov/ct2/show/NCT02311244?term=SUMMER&rank=5. Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published

  4. Acute and recent air pollution exposure and cardiovascular events at labour and delivery

    PubMed Central

    Männistö, Tuija; Mendola, Pauline; Grantz, Katherine Laughon; Leishear, Kira; Sundaram, Rajeshwari; Sherman, Seth; Ying, Qi; Liu, Danping

    2017-01-01

    Objective To study the relationship between acute air pollution exposure and cardiovascular events during labour/delivery. Methods The Consortium on Safe Labor (2002–2008), an observational US cohort with 223 502 singleton deliveries provided electronic medical records. Air pollution exposure was estimated by modified Community Multiscale Air Quality models. Cardiovascular events (cardiac failure/arrest, stroke, myocardial infarcts and other events) were recorded in the hospital discharge records for 687 pregnancies (0.3%). Logistic regression with generalised estimating equations estimated the relationship between cardiovascular events and daily air pollutant levels for delivery day and the 7 days preceding delivery. Results Increased odds of cardiovascular events were observed for each IQR increase in exposure to nitric oxides at 5 and 6 days prior to delivery (OR=1.17, 99% CI 1.04 to 1.30 and OR=1.15, 1.03 to 1.28, respectively). High exposure to toxic air pollution species such as ethylbenzene (OR=1.50, 1.08 to 2.09), m-xylene (OR=1.54, 1.11 to 2.13), o-xylene (OR=1.51, 1.09 to 2.09), p-xylene (OR=1.43, 1.03 to 1.99) and toluene (OR=1.42, 1.02 to 1.97) at 5 days prior to delivery were also associated with cardiovascular events. Decreased odds of events were observed with exposure to ozone. Conclusions Air pollution in the days prior to delivery, especially nitrogen oxides and some toxic air pollution species, was associated with increased risk of cardiovascular events during the labour/delivery admission. PMID:26105036

  5. Optical diagnostics of vascular reactions triggered by weak allergens using laser speckle-contrast imaging technique

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kuznetsov, Yu L; Kalchenko, V V; Astaf'eva, N G

    2014-08-31

    The capability of using the laser speckle contrast imaging technique with a long exposure time for visualisation of primary acute skin vascular reactions caused by a topical application of a weak contact allergen is considered. The method is shown to provide efficient and accurate detection of irritant-induced primary acute vascular reactions of skin. The presented technique possesses a high potential in everyday diagnostic practice, preclinical studies, as well as in the prognosis of skin reactions to the interaction with potentially allergenic materials. (laser biophotonics)

  6. The Positive Emotions after Acute Coronary Events behavioral health intervention: Design, rationale, and preliminary feasibility of a factorial design study.

    PubMed

    Huffman, Jeffery C; Albanese, Ariana M; Campbell, Kirsti A; Celano, Christopher M; Millstein, Rachel A; Mastromauro, Carol A; Healy, Brian C; Chung, Wei-Jean; Januzzi, James L; Collins, Linda M; Park, Elyse R

    2017-04-01

    Positive psychological constructs, such as optimism, are associated with greater participation in cardiac health behaviors and improved cardiac outcomes. Positive psychology interventions, which target psychological well-being, may represent a promising approach to improving health behaviors in high-risk cardiac patients. However, no study has assessed whether a positive psychology intervention can promote physical activity following an acute coronary syndrome. In this article we will describe the methods of a novel factorial design study to aid the development of a positive psychology-based intervention for acute coronary syndrome patients and aim to provide preliminary feasibility data on study implementation. The Positive Emotions after Acute Coronary Events III study is an optimization study (planned N = 128), subsumed within a larger multiphase optimization strategy iterative treatment development project. The goal of Positive Emotions after Acute Coronary Events III is to identify the ideal components of a positive psychology-based intervention to improve post-acute coronary syndrome physical activity. Using a 2 × 2 × 2 factorial design, Positive Emotions after Acute Coronary Events III aims to: (1) evaluate the relative merits of using positive psychology exercises alone or combined with motivational interviewing, (2) assess whether weekly or daily positive psychology exercise completion is optimal, and (3) determine the utility of booster sessions. The study's primary outcome measure is moderate-to-vigorous physical activity at 16 weeks, measured via accelerometer. Secondary outcome measures include psychological, functional, and adherence-related behavioral outcomes, along with metrics of feasibility and acceptability. For the primary study outcome, we will use a mixed-effects model with a random intercept (to account for repeated measures) to assess the main effects of each component (inclusion of motivational interviewing in the exercises

  7. Novel lipid mediators promote resolution of acute inflammation: impact of aspirin and statins

    PubMed Central

    Spite, Matthew; Serhan, Charles N.

    2010-01-01

    The resolution of acute inflammation is a process that allows for inflamed tissues to return to homeostasis. Resolution was held to be a passive process, a concept now overturned with new evidence demonstrating that resolution is actively orchestrated by distinct cellular events and endogenous chemical mediators. Among these, lipid mediators, such as the lipoxins, resolvins, protectins and newly identified maresins, have emerged as a novel genus of potent and stereoselective players that counter-regulate excessive acute inflammation and stimulate molecular and cellular events that define resolution. Given that uncontrolled, chronic inflammation is associated with many cardiovascular pathologies, an appreciation of the endogenous pathways and mediators that control timely resolution can open new terrain for therapeutic approaches targeted at stimulating resolution of local inflammation, as well as correcting the impact of chronic inflammation in cardiovascular disorders. Here, we overview and update the biosynthesis and actions of pro-resolving lipid mediators, highlighting their diverse protective roles relevant to vascular systems and their relation to aspirin and statin therapies. PMID:21071715

  8. Statin cost-effectiveness in the United States for people at different vascular risk levels.

    PubMed

    2009-03-01

    Statins reduce the rates of heart attacks, strokes, and revascularization procedures (ie, major vascular events) in a wide range of circumstances. Randomized controlled trial data from 20,536 adults have been used to estimate the cost-effectiveness of prescribing statin therapy in the United States for people at different levels of vascular disease risk and to explore whether wider use of generic statins beyond the populations currently recommended for treatment in clinical guidelines is indicated. Randomized controlled trial data, an internally validated vascular disease model, and US costs of statin therapy and other medical care were used to project lifetime risks of vascular events and evaluate the cost-effectiveness of 40 mg simvastatin daily. For an average of 5 years, allocation to simvastatin reduced the estimated US costs of hospitalizations for vascular events by approximately 20% (95% CI, 15 to 24) in the different subcategories of participants studied. At a daily cost of $1 for 40 mg generic simvastatin, the estimated costs of preventing a vascular death within the 5-year study period ranged from a net saving of $1300 (95% CI, $15,600 saving to $13,200 cost) among participants with a 42% 5-year major vascular event risk to a net cost of $216,500 ($123,700 to $460,000 cost) among those with a 12% 5-year risk. The costs per life year gained with lifetime simvastatin treatment ranged from $2500 (-$40 to $3820) in people aged 40 to 49 years with a 42% 5-year major vascular event risk to $10,990 ($9430 to $14,700) in people aged 70 years and older with a 12% 5-year risk. Treatment with generic simvastatin appears to be cost-effective for a much wider population in the United States than that recommended by current guidelines.

  9. C-reactive Protein as a Predictor of Adverse outcome in Patients with Acute Coronary Syndrome.

    PubMed

    Sheikh, A S; Yahya, S; Sheikh, N S; Sheikh, A A

    2012-01-01

    The acute-phase reactant C-reactive protein (CRP) has been shown to reflect systemic and vascular inflammation and to predict future cardiovascular events. The objective of this study was to evaluate the prognostic value of CRP in predicting cardiovascular outcome in patients presenting with acute coronary syndromes. This prospective, single-centered study was carried out by the Department of Pathology in collaboration with the Department of Cardiology, Bolan Medical College Complex Quetta, Balochistan, Pakistan from January 2009 to December 2009. We studied 963 consecutive patients presenting with chest pain to Accident and Emergency Department. Patients were divided into four groups. Group-1 comprised patients with unstable angina; group-2 included patients with acute ST elevation myocardial infarction (STEMI); group-3 comprised patients with Non-ST elevation myocardial infarction (Non-STEMI) and group-4 was the control group. All four groups were followed-up for 90 days for occurrence of cardiovascular events. The CRP was elevated (>3 mg/L) among 27.6% patients in Group-1; 70.9% in group- 2; 77.9% in group-3 and 5.3% in the control group. Among cases with elevated CRP, 92.1% had a cardiac event compared to 34.3% among patients with CRP £3 mg/L (P < 0.0001). The mortality was significantly higher (P < 0.0001) in group-2 (8.9%) and group-3 (11.9%) as compared to group-1 (2.1%). There was no cardiac event or mortality in Group-4. Elevated CRP is a predictor of adverse outcome in patients with acute coronary syndromes and helps in identifying patients who may be at risk of cardiovascular complications.

  10. Catastrophic health expenditure on acute coronary events in Asia: a prospective study.

    PubMed

    Jan, Stephen; Lee, Stephen W-L; Sawhney, Jitendra P S; Ong, Tiong K; Chin, Chee Tang; Kim, Hyo-Soo; Krittayaphong, Rungroj; Nhan, Vo T; Itoh, Yohji; Huo, Yong

    2016-03-01

    To estimate out-of-pocket costs and the incidence of catastrophic health expenditure in people admitted to hospital with acute coronary syndromes in Asia. Participants were enrolled between June 2011 and May 2012 into this observational study in China, India, Malaysia, Republic of Korea, Singapore, Thailand and Viet Nam. Sites were required to enrol a minimum of 10 consecutive participants who had been hospitalized for an acute coronary syndrome. Catastrophic health expenditure was defined as out-of-pocket costs of initial hospitalization > 30% of annual baseline household income, and it was assessed six weeks after discharge. We assessed associations between health expenditure and age, sex, diagnosis of the index coronary event and health insurance status of the participant, using logistic regression models. Of 12,922 participants, 9370 (73%) had complete data on expenditure. The mean out-of-pocket cost was 3237 United States dollars. Catastrophic health expenditure was reported by 66% (1984/3007) of those without insurance versus 52% (3296/6366) of those with health insurance (P < 0.05). The occurrence of catastrophic expenditure ranged from 80% (1055/1327) in uninsured and 56% (3212/5692) of insured participants in China, to 0% (0/41) in Malaysia. Large variation exists across Asia in catastrophic health expenditure resulting from hospitalization for acute coronary syndromes. While insurance offers some protection, substantial numbers of people with health insurance still incur financial catastrophe.

  11. [Perioperative acute kidney injury and failure].

    PubMed

    Chhor, Vibol; Journois, Didier

    2014-04-01

    Perioperative period is very likely to lead to acute renal failure because of anesthesia (general or perimedullary) and/or surgery which can cause acute kidney injury. Characterization of acute renal failure is based on serum creatinine level which is imprecise during and following surgery. Studies are based on various definitions of acute renal failure with different thresholds which skewed their comparisons. The RIFLE classification (risk, injury, failure, loss, end stage kidney disease) allows clinicians to distinguish in a similar manner between different stages of acute kidney injury rather than using a unique definition of acute renal failure. Acute renal failure during the perioperative period can mainly be explained by iatrogenic, hemodynamic or surgical causes and can result in an increased morbi-mortality. Prevention of this complication requires hemodynamic optimization (venous return, cardiac output, vascular resistance), discontinuation of nephrotoxic drugs but also knowledge of the different steps of the surgery to avoid further degradation of renal perfusion. Diuretics do not prevent acute renal failure and may even push it forward especially during the perioperative period when venous retourn is already reduced. Edema or weight gain following surgery are not correlated with the vascular compartment volume, much less with renal perfusion. Treatment of perioperative acute renal failure is similar to other acute renal failure. Renal replacement therapy must be mastered to prevent any additional risk of hemodynamic instability or hydro-electrolytic imbalance. Copyright © 2014 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  12. MicroRNAs in vascular tissue engineering and post-ischemic neovascularization☆

    PubMed Central

    Caputo, Massimo; Saif, Jaimy; Rajakaruna, Cha; Brooks, Marcus; Angelini, Gianni D.; Emanueli, Costanza

    2015-01-01

    Increasing numbers of paediatric patients with congenital heart defects are surviving to adulthood, albeit with continuing clinical needs. Hence, there is still scope for revolutionary new strategies to correct vascular anatomical defects. Adult patients are also surviving longer with the adverse consequences of ischemic vascular disease, especially after acute coronary syndromes brought on by plaque erosion and rupture. Vascular tissue engineering and therapeutic angiogenesis provide new hope for these patients. Both approaches have shown promise in laboratory studies, but have not yet been able to deliver clear evidence of clinical success. More research into biomaterials, molecular medicine and cell and molecular therapies is necessary. This review article focuses on the new opportunities offered by targeting microRNAs for the improved production and greater empowerment of vascular cells for use in vascular tissue engineering or for increasing blood perfusion of ischemic tissues by amplifying the resident microvascular network. PMID:25980937

  13. Redox-dependent impairment of vascular function in sickle cell disease.

    PubMed

    Aslan, Mutay; Freeman, Bruce A

    2007-12-01

    The vascular pathophysiology of sickle cell disease (SCD) is influenced by many factors, including adhesiveness of red and white blood cells to endothelium, increased coagulation, and homeostatic perturbation. The vascular endothelium is central to disease pathogenesis because it displays adhesion molecules for blood cells, balances procoagulant and anticoagulant properties of the vessel wall, and regulates vascular homeostasis by synthesizing vasoconstricting and vasodilating substances. The occurrence of intermittent vascular occlusion in SCD leads to reperfusion injury associated with granulocyte accumulation and enhanced production of reactive oxygen species. The participation of nitric oxide (NO) in oxidative reactions causes a reduction in NO bioavailability and contributes to vascular dysfunction in SCD. Therapeutic strategies designed to counteract endothelial, inflammatory, and oxidative abnormalities may reduce the frequency of hospitalization and blood transfusion, the incidence of pain, and the occurrence of acute chest syndrome and pulmonary hypertension in patients with SCD.

  14. Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke

    PubMed Central

    Chiva-Blanch, Gemma; Suades, Rosa; Crespo, Javier; Peña, Esther; Padró, Teresa; Jiménez-Xarrié, Elena; Martí-Fàbregas, Joan; Badimon, Lina

    2016-01-01

    Purpose Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke. Methods Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3–7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells) were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls. Results Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions. Conclusions Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process

  15. Measuring Cognitive and Affective Constructs in the Context of an Acute Health Event

    PubMed Central

    Boudreaux, Edwin D.; Moon, Simon; Tappe, Karyn A.; Bock, Beth; Baumann, Brigitte; Chapman, Gretchen B.

    2013-01-01

    The latest recommendations for building dynamic health behavior theories emphasize that cognitions, emotions, and behaviors – and the nature of their inter-relationships -- can change over time. This paper describes the development and psychometric validation of four scales created to measure smoking-related causal attributions, perceived illness severity, event-related emotions, and intention to quit smoking among patients experiencing acute cardiac symptoms. After completing qualitative work with a sample of 50 cardiac patients, we administered the scales to 300 patients presenting to the emergency department for cardiac-related symptoms. Factor analyses, alpha coefficients, ANOVAS, and Pearson correlation coefficients were used to establish the scales' reliability and validity. Factor analyses revealed a stable factor structures for each of the four constructs. The scales were internally consistent, with the majority having an alpha of >0.80 (range: 0.57 to 0.89). Mean differences in ratings of the perceived illness severity and event-related emotions were noted across the three time anchors. Significant increases in intention to quit at the time of enrollment, compared to retrospective ratings of intention to quit before the event, provide preliminary support for the sensitivity of this measure to the motivating impact of the event. Finally, smoking-related causal attributions, perceived illness severity, and event-related emotions correlated in the expected directions with intention to quit smoking, providing preliminary support for construct validity. PMID:22970703

  16. Role of central obesity in risk stratification after an acute coronary event: does central obesity add prognostic value to the Global Registry of Acute Coronary Events (GRACE) risk score in patients with acute coronary syndrome?

    PubMed

    Martins, Albino; Ribeiro, Sílvia; Gonçalves, Pierre; Correia, Adelino

    2013-10-01

    Accurate risk stratification is an important step in the initial management of acute coronary syndrome (ACS), and current guidelines recommend the use of risk scores, such as the Global Registry of Acute Coronary Events risk score (GRACE RS). Recent studies have suggested that abdominal obesity is associated with cardiovascular events in patients with ACS. However, little is known about the additional value of abdominal obesity beyond risk scores. The aim of our study was thus to assess whether waist circumference, a surrogate of abdominal adiposity, adds prognostic information to the GRACE RS. This was a retrospective cohort study of ACS patients admitted consecutively to a cardiac care unit between June 2009 and July 2010. The composite of all-cause mortality or myocardial reinfarction within six months of index hospitalization was used as the endpoint for the analysis. A total of 285 patients were studied, 96.1% admitted for myocardial infarction (with or without ST elevation) and 3.9% for unstable angina. At the end of the follow-up period, 10 patients had died and the composite endpoint had been reached in 27 patients (9.5%). More than 70% of the study population were obese or overweight, and abdominal obesity was present in 44.6%. The GRACE RS showed poor predictive accuracy (area under the curve 0.60), and most of the GRACE variables did not reach statistical significance in multivariate analysis. The addition of waist circumference to the GRACE RS did not improve its discriminatory performance. Abdominal obesity does not add prognostic information to the GRACE RS to predict six-month mortality or myocardial reinfarction.

  17. Acute Kidney Injury and Risk of Heart Failure and Atherosclerotic Events.

    PubMed

    Go, Alan S; Hsu, Chi-Yuan; Yang, Jingrong; Tan, Thida C; Zheng, Sijie; Ordonez, Juan D; Liu, Kathleen D

    2018-06-07

    AKI in the hospital is common and is associated with excess mortality. We examined whether AKI is also independently associated with a higher risk of different cardiovascular events in the first year after discharge. We conducted a retrospective analysis of a cohort between 2006 and 2013 with follow-up through 2014, within Kaiser Permanente Northern California. We identified all adults admitted to 21 hospitals who had one or more in-hospital serum creatinine test result and survived to discharge. Occurrence of AKI was on the basis of Kidney Disease: Improving Global Outcomes diagnostic criteria. Potential confounders were identified from comprehensive inpatient and outpatient, laboratory, and pharmacy electronic medical records. During the 365 days after discharge, we ascertained occurrence of heart failure, acute coronary syndromes, peripheral artery disease, and ischemic stroke events from electronic medical records. Among a matched cohort of 146,941 hospitalized adults, 31,245 experienced AKI. At 365 days postdischarge, AKI was independently associated with higher rates of the composite outcome of hospitalization for heart failure and atherosclerotic events (adjusted hazard ratio [aHR], 1.18; 95% confidence interval [95% CI], 1.13 to 1.25) even after adjustment for demographics, comorbidities, preadmission eGFR and proteinuria, heart failure and sepsis complicating the hospitalization, intensive care unit (ICU) admission, length of stay, and predicted in-hospital mortality. This was driven by an excess risk of subsequent heart failure (aHR, 1.44; 95% CI, 1.33 to 1.56), whereas there was no significant association with follow-up atherosclerotic events (aHR, 1.05; 95% CI, 0.98 to 1.12). AKI is independently associated with a higher risk of cardiovascular events, especially heart failure, after hospital discharge. Copyright © 2018 by the American Society of Nephrology.

  18. Vascular retraction driven by matrix softening

    NASA Astrophysics Data System (ADS)

    Valentine, Megan

    We recently discovered we can directly apply physical forces and monitor the downstream responses in a living organism in real time through manipulation of the blood vessels of a marine organism called, Botryllus schlosseri. The extracellular matrix (ECM) plays a key role in regulating vascular growth and homeostasis in Botryllus,a basal chordate which has a large, transparent extracorporeal vascular network that can encompass areas >100 cm2. We have determined that lysyl oxidase 1 (LOX1), which is responsible for cross-linking collagen, is expressed in all vascular cells and is critically important for vascular maintenance. Inhibition of LOX1 activity in vivo by the addition of a specific inhibitor, ß-aminopropionitrile (BAPN), caused a rapid, global regression of the entire vascular bed, with some vessels regressing >10 mm within 16 hrs. In this talk, I will discuss the molecular and cellular origins of this systemic remodeling event, which hinges upon the ability of the vascular cells to sense and respond to mechanical signals, while introducing this exciting new model system for studies of biological physics and mechanobiology. Collaborators: Anthony DeTomaso, Delany Rodriguez, Aimal Khankhel (UCSB).

  19. Acute cardiovascular events and all-cause mortality in patients with hyperthyroidism: a population-based cohort study.

    PubMed

    Dekkers, Olaf M; Horváth-Puhó, Erzsébet; Cannegieter, Suzanne C; Vandenbroucke, Jan P; Sørensen, Henrik Toft; Jørgensen, Jens Otto L

    2017-01-01

    Several studies have shown an increased risk for cardiovascular disease (CVD) in hyperthyroidism, but most studies have been too small to address the effect of hyperthyroidism on individual cardiovascular endpoints. Our main aim was to assess the association among hyperthyroidism, acute cardiovascular events and mortality. It is a nationwide population-based cohort study. Data were obtained from the Danish Civil Registration System and the Danish National Patient Registry, which covers all Danish hospitals. We compared the rate of all-cause mortality as well as venous thromboembolism (VTE), acute myocardial infarction (AMI), ischemic and non-ischemic stroke, arterial embolism, atrial fibrillation (AF) and percutaneous coronary intervention (PCI) in the two cohorts. Hazard ratios (HR) with 95% confidence intervals (95% CI) were estimated. The study included 85 856 hyperthyroid patients and 847 057 matched population-based controls. Mean follow-up time was 9.2 years. The HR for mortality was highest in the first 3 months after diagnosis of hyperthyroidism: 4.62, 95% CI: 4.40-4.85, and remained elevated during long-term follow-up (>3 years) (HR: 1.35, 95% CI: 1.33-1.37). The risk for all examined cardiovascular events was increased, with the highest risk in the first 3 months after hyperthyroidism diagnosis. The 3-month post-diagnosis risk was highest for atrial fibrillation (HR: 7.32, 95% CI: 6.58-8.14) and arterial embolism (HR: 6.08, 95% CI: 4.30-8.61), but the risks of VTE, AMI, ischemic and non-ischemic stroke and PCI were increased also 2- to 3-fold. We found an increased risk for all-cause mortality and acute cardiovascular events in patients with hyperthyroidism. © 2017 European Society of Endocrinology.

  20. The vascular basement membrane in the healthy and pathological brain.

    PubMed

    Thomsen, Maj S; Routhe, Lisa J; Moos, Torben

    2017-10-01

    The vascular basement membrane contributes to the integrity of the blood-brain barrier (BBB), which is formed by brain capillary endothelial cells (BCECs). The BCECs receive support from pericytes embedded in the vascular basement membrane and from astrocyte endfeet. The vascular basement membrane forms a three-dimensional protein network predominantly composed of laminin, collagen IV, nidogen, and heparan sulfate proteoglycans that mutually support interactions between BCECs, pericytes, and astrocytes. Major changes in the molecular composition of the vascular basement membrane are observed in acute and chronic neuropathological settings. In the present review, we cover the significance of the vascular basement membrane in the healthy and pathological brain. In stroke, loss of BBB integrity is accompanied by upregulation of proteolytic enzymes and degradation of vascular basement membrane proteins. There is yet no causal relationship between expression or activity of matrix proteases and the degradation of vascular matrix proteins in vivo. In Alzheimer's disease, changes in the vascular basement membrane include accumulation of Aβ, composite changes, and thickening. The physical properties of the vascular basement membrane carry the potential of obstructing drug delivery to the brain, e.g. thickening of the basement membrane can affect drug delivery to the brain, especially the delivery of nanoparticles.

  1. Evidence Linking Hypoglycemic Events to an Increased Risk of Acute Cardiovascular Events in Patients With Type 2 Diabetes

    PubMed Central

    Johnston, Stephen S.; Conner, Christopher; Aagren, Mark; Smith, David M.; Bouchard, Jonathan; Brett, Jason

    2011-01-01

    OBJECTIVE This retrospective study examined the association between ICD-9-CM–coded outpatient hypoglycemic events (HEs) and acute cardiovascular events (ACVEs), i.e., acute myocardial infarction, coronary artery bypass grafting, revascularization, percutaneous coronary intervention, and incident unstable angina, in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Data were derived from healthcare claims for individuals with employer-sponsored primary or Medicare supplemental insurance. A baseline period (30 September 2006 to 30 September 2007) was used to identify eligible patients and collect information on their clinical and demographic characteristics. An evaluation period (1 October 2007 to 30 September 2008) was used to identify HEs and ACVEs. Patients aged ≥18 years with type 2 diabetes were selected for analysis by a modified Healthcare Effectiveness Data and Information Set algorithm. Data were analyzed with multiple logistic regression and backward stepwise selection (maximum P = 0.01) with adjustment for important confounding variables, including age, sex, geography, insurance type, comorbidity scores, cardiovascular risk factors, diabetes complications, total baseline medical expenditures, and prior ACVEs. RESULTS Of the 860,845 patients in the analysis set, 27,065 (3.1%) had ICD-9-CM–coded HEs during the evaluation period. The main model retained 17 significant independent variables. Patients with HEs had 79% higher regression-adjusted odds (HE odds ratio [OR] 1.79; 95% CI 1.69–1.89) of ACVEs than patients without HEs; results in patients aged ≥65 years were similar to those for the entire population (HE OR 1.78, 95% CI 1.65–1.92). CONCLUSIONS ICD-9-CM–coded HEs were independently associated with an increased risk of ACVEs. Further studies of the relationship between hypoglycemia and the risk of ACVEs are warranted. PMID:21421802

  2. Association of diet, exercise, and smoking modification with risk of early cardiovascular events after acute coronary syndromes.

    PubMed

    Chow, Clara K; Jolly, Sanjit; Rao-Melacini, Purnima; Fox, Keith A A; Anand, Sonia S; Yusuf, Salim

    2010-02-16

    Although preventive drug therapy is a priority after acute coronary syndrome, less is known about adherence to behavioral recommendations. The aim of this study was to examine the influence of adherence to behavioral recommendations in the short term on risk of cardiovascular events. The study population included 18 809 patients from 41 countries enrolled in the Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS) 5 randomized clinical trial. At the 30-day follow-up, patients reported adherence to diet, physical activity, and smoking cessation. Cardiovascular events (myocardial infarction, stroke, cardiovascular death) and all-cause mortality were documented to 6 months. About one third of smokers persisted in smoking. Adherence to neither diet nor exercise recommendations was reported by 28.5%, adherence to either diet or exercise by 41.6%, and adherence to both by 29.9%. In contrast, 96.1% of subjects reported antiplatelet use, 78.9% reported statin use, and 72.4% reported angiotensin-converting enzyme/angiotensin receptor blocker use. Quitting smoking was associated with a decreased risk of myocardial infarction compared with persistent smoking (odds ratio, 0.57; 95% confidence interval, 0.36 to 0.89). Diet and exercise adherence was associated with a decreased risk of myocardial infarction compared with nonadherence (odds ratio, 0.52; 95% confidence interval, 0.4 to 0.69). Patients who reported persistent smoking and nonadherence to diet and exercise had a 3.8-fold (95% confidence interval, 2.5 to 5.9) increased risk of myocardial infarction/stroke/death compared with never smokers who modified diet and exercise. Adherence to behavioral advice (diet, exercise, and smoking cessation) after acute coronary syndrome was associated with a substantially lower risk of recurrent cardiovascular events. These findings suggest that behavioral modification should be given priority similar to other preventive medications immediately after acute coronary

  3. Brain magnetic resonance imaging findings fail to suspect Fabry disease in young patients with an acute cerebrovascular event.

    PubMed

    Fazekas, Franz; Enzinger, Christian; Schmidt, Reinhold; Grittner, Ulrike; Giese, Anne-Katrin; Hennerici, Michael G; Huber, Roman; Jungehulsing, Gerhard J; Kaps, Manfred; Kessler, Christof; Martus, Peter; Putaala, Jukka; Ropele, Stefan; Tanislav, Christian; Tatlisumak, Turgut; Thijs, Vincent; von Sarnowski, Bettina; Norrving, Bo; Rolfs, Arndt

    2015-06-01

    Fabry disease (FD) may cause stroke and is reportedly associated with typical brain findings on magnetic resonance imaging (MRI). In a large group of young patients with an acute cerebrovascular event, we wanted to test whether brain MRI findings can serve to suggest the presence of FD. The Stroke in Young Fabry Patients (SIFAP 1) study prospectively collected clinical, laboratory, and radiological data of 5023 patients (18-55 years) with an acute cerebrovascular event. Their MRI was interpreted centrally and blinded to all other information. Biochemical findings and genetic testing served to diagnose FD in 45 (0.9%) patients. We compared the imaging findings between FD and non-FD patients in patients with at least a T2-weighted MRI of good quality. A total of 3203 (63.8%) patients had the required MRI data set. Among those were 34 patients with a diagnosis of FD (1.1%), which was definite in 21 and probable in 13 cases. The median age of patients with FD was slightly lower (45 versus 46 years) and women prevailed (70.6% versus 40.7%; P<0.001). Presence or extent of white matter hyperintensities, infarct localization, vertebrobasilar artery dilatation, T1-signal hyperintensity of the pulvinar thalami, or any other MRI finding did not distinguish patients with FD from non-FD cerebrovascular event patients. Pulvinar hyperintensity was not present in a single patient with FD but seen in 6 non-FD patients. Brain MRI findings cannot serve to suspect FD in young patients presenting with an acute cerebrovascular event. This deserves consideration in the search for possible causes of young patients with stroke. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583. © 2015 American Heart Association, Inc.

  4. Diagnosis and treatment of vascular damage in dementia.

    PubMed

    Biessels, Geert Jan

    2016-05-01

    This paper provides an overview of cognitive impairment due to vascular brain damage, which is referred to as vascular cognitive impairment (VCI). Over the past decades, we have seen marked progress in detecting VCI, both through maturation of diagnostic concepts and through advances in brain imaging, especially MRI. Yet in daily practice, it is often challenging to establish the diagnosis, particularly in patients where there is no evident temporal relation between a cerebrovascular event and cognitive dysfunction. Because vascular damage is such a common cause of cognitive dysfunction, it provides an obvious target for treatment. In patients whose cognitive dysfunction follows directly after a stroke, the etiological classification of this stroke will direct treatment. In many patients however, VCI develops due to so-called "silent vascular damage," without evident cerebrovascular events. In these patients, small vessel diseases (SVDs) are the most common cause. Yet no SVD-specific treatments currently exist, which is due to incomplete understanding of the pathophysiology. This review addresses developments in this field. It offers a framework to translate diagnostic criteria to daily practice, addresses treatment, and highlights some future perspectives. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau, and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Regulation and function of endothelial glycocalyx layer in vascular diseases.

    PubMed

    Sieve, Irina; Münster-Kühnel, Anja K; Hilfiker-Kleiner, Denise

    2018-01-01

    In the vascular system, the endothelial surface layer (ESL) as the inner surface of blood vessels affects mechanotransduction, vascular permeability, rheology, thrombogenesis, and leukocyte adhesion. It creates barriers between endothelial cells and blood and neighbouring cells. The glycocalyx, composed of glycoconjugates and proteoglycans, is an integral component of the ESL and a key element in inter- and intracellular communication and tissue homeostasis. In pathophysiological conditions (atherosclerosis, infection, ischemia/reperfusion injury, diabetes, trauma and acute lung injury) glycocalyx-degrading factors, i.e. reactive oxygen and nitrogen species, matrix metalloproteinases, heparanase and sialidases, damage the ESL, thereby impairing endothelial functions. This leads to increased capillary permeability, leucocyte-endothelium interactions, thrombosis and vascular inflammation, the latter further driving glycocalyx destruction. The present review highlights current knowledge on the vasculoprotective role of the ESL, with specific emphasis on its remodelling in inflammatory vascular diseases and discusses its potential as a novel therapeutic target to treat vascular pathologies. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Immediate and long-term consequences of vascular toxicity during zebrafish development

    EPA Science Inventory

    Proper formation of the vascular system is necessary for embryogenesis, and chemical disruption of vascular development may be a key event driving developmental toxicity. In order to test the effect of environmental chemicals on this critical process, we developed a quantitative ...

  7. Arf Suppresses Hepatic Vascular Neoplasia in a Carcinogen-Exposed Murine Model

    PubMed Central

    Busch, Stephanie E; Gurley, Kay E; Moser, Russell D; Kemp, Christopher J

    2013-01-01

    Hepatic haemangiosarcoma is a deadly malignancy whose aetiology remains poorly understood. Inactivation of the CDKN2A locus, which houses the ARF and p16INK4a tumour suppressor genes, is a common event in haemangiosarcoma patients, but the precise role of ARF in vascular tumourigenesis is unknown. To determine the extent to which ARF suppresses vascular neoplasia, we examined the incidence of hepatic vascular lesions in Arf-deficient mice exposed to the carcinogen urethane (i.p. 1 mg/g). Loss of Arf resulted in elevated morbidity and increased the incidence of both haemangiomas and incipient haemangiosarcomas. Suppression of vascular lesion development by ARF was heavily dependent on both Arf gene-dosage and the genetic strain of the mouse. Trp53-deficient mice also developed hepatic vascular lesions after exposure to urethane, suggesting that ARF signals through a p53-dependent pathway to inhibit the development of hepatic haemangiosarcoma. Our findings provide strong evidence that inactivation of Arf is a causative event in vascular neoplasia and suggest that the ARF pathway may be a novel molecular target for therapeutic intervention in haemangiosarcoma patients. PMID:22430984

  8. Catastrophic health expenditure on acute coronary events in Asia: a prospective study

    PubMed Central

    Lee, Stephen W-L; Sawhney, Jitendra PS; Ong, Tiong K; Chin, Chee Tang; Kim, Hyo-Soo; Krittayaphong, Rungroj; Nhan, Vo T; Itoh, Yohji; Huo, Yong

    2016-01-01

    Abstract Objective To estimate out-of-pocket costs and the incidence of catastrophic health expenditure in people admitted to hospital with acute coronary syndromes in Asia. Methods Participants were enrolled between June 2011 and May 2012 into this observational study in China, India, Malaysia, Republic of Korea, Singapore, Thailand and Viet Nam. Sites were required to enrol a minimum of 10 consecutive participants who had been hospitalized for an acute coronary syndrome. Catastrophic health expenditure was defined as out-of-pocket costs of initial hospitalization > 30% of annual baseline household income, and it was assessed six weeks after discharge. We assessed associations between health expenditure and age, sex, diagnosis of the index coronary event and health insurance status of the participant, using logistic regression models. Findings Of 12 922 participants, 9370 (73%) had complete data on expenditure. The mean out-of-pocket cost was 3237 United States dollars. Catastrophic health expenditure was reported by 66% (1984/3007) of those without insurance versus 52% (3296/6366) of those with health insurance (P < 0.05). The occurrence of catastrophic expenditure ranged from 80% (1055/1327) in uninsured and 56% (3212/5692) of insured participants in China, to 0% (0/41) in Malaysia. Conclusion Large variation exists across Asia in catastrophic health expenditure resulting from hospitalization for acute coronary syndromes. While insurance offers some protection, substantial numbers of people with health insurance still incur financial catastrophe. PMID:26966330

  9. Adverse events associated with single dose oral analgesics for acute postoperative pain in adults - an overview of Cochrane reviews.

    PubMed

    Moore, R Andrew; Derry, Sheena; Aldington, Dominic; Wiffen, Philip J

    2015-10-13

    This is an update of a Cochrane overview published in Issue 9, 2011; that overview considered both efficacy and adverse events. This overview considers adverse events, with efficacy dealt with in a separate overview.Thirty-nine Cochrane reviews of randomised trials have examined the adverse events associated with individual drug interventions in acute postoperative pain. This overview brings together the results of those individual reviews. To provide an overview of adverse event rates associated with single-dose oral analgesics, compared with placebo, for acute postoperative pain in adults. We identified systematic reviews in The Cochrane Database of Systematic Reviews on The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group. We extracted information related to participants experiencing any adverse event, and reports of serious adverse events, and deaths from the individual reviews. Information was available from 39 Cochrane reviews for 41 different analgesics or analgesic combinations (51 drug/dose/formulations) tested in single oral doses in participants with moderate or severe postoperative pain. This involved around 350 unique studies involving about 35,000 participants. Most studies involved younger participants with pain following removal of molar teeth.For most nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, and combinations not containing opioids, there were few examples where participants experienced significantly more or fewer adverse events than with placebo. For aspirin 1000 mg and diflunisal 1000 mg, opioids, or fixed-dose combination drugs containing opioids, participants typically experienced significantly more adverse events than with placebo. Studies of combinations of ibuprofen and paracetamol reported significantly fewer adverse events.Serious adverse events were rare, occurring a rate of about 1 in 3200 participants.Most reviews did not report specific adverse events. Despite

  10. Visualizing the Acute Effects of Vascular-Targeted Therapy In Vivo Using Intravital Microscopy and Magnetic Resonance Imaging: Correlation with Endothelial Apoptosis, Cytokine Induction, and Treatment Outcome1

    PubMed Central

    Seshadri, Mukund; Spernyak, Joseph A; Maiery, Patricia G; Cheney, Richard T; Mazurchuk, Richard; Bellnier, David A

    2007-01-01

    Abstract The acute effects of the vascular-disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) were investigated in vivo using intravital microscopy (IVM) and magnetic resonance imaging (MRI). Changes in vascular permeability and blood flow of syngeneic CT-26 murine colon adenocarcinomas were assessed at 4 and 24 hours after DMXAA treatment (30 mg/kg, i.p.) and correlated with induction of tumor necrosis factor-α (TNF-α), endothelial damage [CD31/terminal deoxynucleotidyl transferase (TdT)], and treatment outcome. Intravital imaging revealed a marked increase in vascular permeability 4 hours after treatment, consistent with increases in intratumoral mRNA and protein levels of TNF-α. Parallel contrast-enhanced MRI studies showed a ∼ 4-fold increase in longitudinal relaxation rates (ΔR1), indicative of increased contrast agent accumulation within the tumor. Dual immunostained tumor sections (CD31/TdT) revealed evidence of endothelial apoptosis at this time point. Twenty-four hours after treatment, extensive hemorrhage and complete disruption of vascular architecture were observed with IVM, along with a significant reduction in ΔR1; and virtual absence of CD31 immunostaining. DMXAA-induced tumor vascular damage resulted in significant long-term (60-day) cures compared to untreated controls. Multimodality imaging approaches are useful in visualizing the effects of antivascular therapy in vivo. Such approaches allow cross validation and correlation of findings with underlying molecular changes contributing to treatment outcome. PMID:17356709

  11. Simultaneous acute deep vein thrombosis and acute brucellosis. A case report.

    PubMed

    Salihi, Salih; Andaç, Şeyda; Kalender, Mehmet; Yıldırım, Onur; İmre, Ayfer

    2016-06-01

    Brucellosis is a zoonotic disease common in developing countries. Vascular complications, including arterial and venous, associated with Brucella infection have rarely been reported. A case of deep venous thrombosis (DVT) developing after a diagnosis of acute brucellosis in a young milkman is presented. A 26-year-old man presented with pain in the right leg. The patient's medical history included a diagnosis of brucellosis in our hospital where he had presented with complaints of weakness and fever. Peripheral venous Doppler ultrasound showed DVT, and the patient was treated with anticoagulants. The patient was discharged with warfarin therapy and anti-brucellosis treatment. Although rare, some infectious agents may cause vascular pathologies. Patients presenting with symptoms of DVT or similar vascular pathologies should be assessed for infectious agents, particularly in those coming from Brucella-endemic areas.

  12. C-reactive Protein as a Predictor of Adverse outcome in Patients with Acute Coronary Syndrome

    PubMed Central

    Sheikh, A. S.; Yahya, S.; Sheikh, N. S.; Sheikh, A. A

    2012-01-01

    Background and Objectives: The acute-phase reactant C-reactive protein (CRP) has been shown to reflect systemic and vascular inflammation and to predict future cardiovascular events. The objective of this study was to evaluate the prognostic value of CRP in predicting cardiovascular outcome in patients presenting with acute coronary syndromes. Patients and Methods: This prospective, single-centered study was carried out by the Department of Pathology in collaboration with the Department of Cardiology, Bolan Medical College Complex Quetta, Balochistan, Pakistan from January 2009 to December 2009. We studied 963 consecutive patients presenting with chest pain to Accident and Emergency Department. Patients were divided into four groups. Group-1 comprised patients with unstable angina; group-2 included patients with acute ST elevation myocardial infarction (STEMI); group-3 comprised patients with Non-ST elevation myocardial infarction (Non-STEMI) and group-4 was the control group. All four groups were followed-up for 90 days for occurrence of cardiovascular events. Results: The CRP was elevated (>3 mg/L) among 27.6% patients in Group-1; 70.9% in group- 2; 77.9% in group-3 and 5.3% in the control group. Among cases with elevated CRP, 92.1% had a cardiac event compared to 34.3% among patients with CRP £3 mg/L (P < 0.0001). The mortality was significantly higher (P < 0.0001) in group-2 (8.9%) and group-3 (11.9%) as compared to group-1 (2.1%). There was no cardiac event or mortality in Group-4. Conclusions: Elevated CRP is a predictor of adverse outcome in patients with acute coronary syndromes and helps in identifying patients who may be at risk of cardiovascular complications. PMID:22754634

  13. Positioning Vascularized Composite Allotransplantation within the Spectrum of Solid Organ Transplantation

    DTIC Science & Technology

    2014-10-01

    vasculopathy. Initial IR-ICG imaging studies of graft perfusion correlate well with acute graft rejection in our animals. Finally in Aim 8 we will develop...multiple acute rejection activities, and can be exacerbated to confluent aggressive vasculopathy by non-alloimmune triggers. We will perform vascular...chronic osteomyelitis in heel, eligible for listing for hand transplant, will wait until rehab of prosthesis for lower limb is complete Male age 32

  14. Acute resistance exercise reduces blood pressure and vascular reactivity, and increases endothelium-dependent relaxation in spontaneously hypertensive rats.

    PubMed

    Faria, Thaís de Oliveira; Targueta, Gabriel Pelegrineti; Angeli, Jhuli Keli; Almeida, Edna Aparecida Silveira; Stefanon, Ivanita; Vassallo, Dalton Valentim; Lizardo, Juliana Hott de Fúcio

    2010-09-01

    The aim of the present study was to assess the effects of acute dynamic resistance exercise on resting blood pressure (BP) and on endothelial function of vascular bed of spontaneously hypertensive rats. Hemodynamic measurements were performed before and after acute dynamic resistance exercise in conscious animals. After exercise, the tail artery was cannulated for mean perfusion pressure with constant flow measurement and for performing concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP) and dose-response curves to phenylephrine (PHE). PHE protocol was also repeated with damaged endothelium and after L-NAME and indomethacin perfusion on the tail. The maximal response (E(max)) and sensitivity (pD(2)) were evaluated to these drugs. Exercise reduced resting systolic and diastolic BP (Delta -79 +/- 1.8; -23 +/- 2.3 mmHg, respectively; P < 0.05). ACh-induced relaxation increased in the exercise group (pD(2) = 9.8 +/- 0.06, P < 0.05) when compared with control rats (pD(2) = 8.7 +/- 0.1). The E(max) to PHE with intact endothelium decreased following exercise condition (439 +/- 18 mmHg, P < 0.05) when compared with control rats (276 +/- 22 mmHg). This response was abolished after L-NAME and indomethacin administration. After damage of the endothelium, PHE responses were not significantly different between the groups; however, E(max) and pD(2) increased when compared with responses obtained with intact endothelium. The results demonstrated that acute dynamic resistance exercise decreased resting BP and reactivity to PHE and increased endothelium-dependent relaxation. Nitric oxide and vasodilators prostanoids appear to be involved in post-exercise endothelial and pressor responses.

  15. Deleterious vascular effects of indoxyl sulfate and reversal by oral adsorbent AST-120.

    PubMed

    Six, Isabelle; Gross, Priscilla; Rémond, Mathieu C; Chillon, Jean Marc; Poirot, Sabrina; Drueke, Tilman B; Massy, Ziad A

    2015-11-01

    In chronic kidney disease (CKD), blood vessels are permanently exposed to uremic toxins such as indoxyl sulfate (IS). We hypothesized that IS could alter vascular tone and that reducing its serum concentration could be beneficial. We studied acute and longer-term effects of IS and AST-120, an oral charcoal adsorbent, on vascular reactivity, endothelium integrity and expression of adhesion molecules VCAM-1 and ICAM-1 in aortic rings of normal and uremic wild type (WT) mice in vitro, and the cardiovascular effects of AST-120 in both WT and apoE-/- mice with CKD in vivo. In vitro, 1.0 mM IS acutely reduced vascular relaxation (64% for IS 1.0 mM vs. 80% for control, p < 0.05). The effect was more marked after 4 days exposure (39% for IS 1.0 mM 4 days; p < 0.001, prolonged vs. acute exposure), and was associated with endothelial cell loss and upregulation of ICAM-1/VCAM-1 expression. In vitro, AST-120 restored normal vascular function and prevented IS induced endothelial cell loss and ICAM-1/VCAM-1 upregulation. In vivo, AST-120 treatment of CKD mice (1) improved vascular relaxation (72% vs. 48% maximal relaxation in treated vs. untreated mice, p < 0.001), (2) reduced aortic VCAM-1 and ICAM-1 expression, (3) decreased aorta systolic expansion rate (9 ± 3% CKD vs. 14 ± 3% CKD + AST-120, p < 0.02), and (4) prevented the increase in pulse wave velocity (3.56 ± 0.17 m/s CKD vs. 3.10 ± 0.08 m/s CKD + AST-120, p < 0.006). Similar changes were observed in apoE-/- mice. IS appears to be an important contributor to the vascular dysfunction associated with CKD. AST-120 treatment ameliorates this dysfunction, possibly via a decrease in serum IS concentration. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Obesity-induced adipokine imbalance impairs mouse pulmonary vascular endothelial function and primes the lung for injury.

    PubMed

    Shah, Dilip; Romero, Freddy; Duong, Michelle; Wang, Nadan; Paudyal, Bishnuhari; Suratt, Benjamin T; Kallen, Caleb B; Sun, Jianxin; Zhu, Ying; Walsh, Kenneth; Summer, Ross

    2015-06-12

    Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese mice expressed higher levels of leukocyte adhesion markers and lower levels of cell-cell junctional proteins when compared to lean mice. We tested whether systemic factors are responsible for these alterations in the pulmonary endothelium; treatment of primary lung endothelial cells with obese serum enhanced the expression of adhesion proteins and reduced the expression of endothelial junctional proteins when compared to lean serum. Alterations in pulmonary endothelial cells observed in obese mice were associated with enhanced susceptibility to LPS-induced lung injury. Restoring serum adiponectin levels reversed the effects of obesity on the lung endothelium and attenuated susceptibility to acute injury. Our work indicates that obesity impairs pulmonary vascular homeostasis and enhances susceptibility to acute injury and provides mechanistic insight into the increased prevalence of ARDS in obese humans.

  17. Obesity-induced adipokine imbalance impairs mouse pulmonary vascular endothelial function and primes the lung for injury

    PubMed Central

    Shah, Dilip; Romero, Freddy; Duong, Michelle; Wang, Nadan; Paudyal, Bishnuhari; Suratt, Benjamin T.; Kallen, Caleb B.; Sun, Jianxin; Zhu, Ying; Walsh, Kenneth; Summer, Ross

    2015-01-01

    Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese mice expressed higher levels of leukocyte adhesion markers and lower levels of cell-cell junctional proteins when compared to lean mice. We tested whether systemic factors are responsible for these alterations in the pulmonary endothelium; treatment of primary lung endothelial cells with obese serum enhanced the expression of adhesion proteins and reduced the expression of endothelial junctional proteins when compared to lean serum. Alterations in pulmonary endothelial cells observed in obese mice were associated with enhanced susceptibility to LPS-induced lung injury. Restoring serum adiponectin levels reversed the effects of obesity on the lung endothelium and attenuated susceptibility to acute injury. Our work indicates that obesity impairs pulmonary vascular homeostasis and enhances susceptibility to acute injury and provides mechanistic insight into the increased prevalence of ARDS in obese humans. PMID:26068229

  18. Calcium Channel Blockers in Secondary Cardiovascular Prevention and Risk of Acute Events: Real-World Evidence from Nested Case-Control Studies on Italian Hypertensive Elderly.

    PubMed

    Bettiol, Alessandra; Lucenteforte, Ersilia; Vannacci, Alfredo; Lombardi, Niccolò; Onder, Graziano; Agabiti, Nera; Vitale, Cristiana; Trifirò, Gianluca; Corrao, Giovanni; Roberto, Giuseppe; Mugelli, Alessandro; Chinellato, Alessandro

    2017-12-01

    Antihypertensive treatment with calcium channel blockers (CCBs) is consolidated in clinical practice; however, different studies observed increased risks of acute events for short-acting CCBs. This study aimed to provide real-world evidence on risks of acute cardiovascular (CV) events, hospitalizations and mortality among users of different CCB classes in secondary CV prevention. Three case-control studies were nested in a cohort of Italian elderly hypertensive CV-compromised CCBs users. Cases were subjects with CV events (n = 25,204), all-cause hospitalizations (n = 19,237), or all-cause mortality (n = 17,996) during the follow-up. Up to four controls were matched for each case. Current or past exposition to CCBs at index date was defined based on molecule, formulation and daily doses of the last CCB delivery. The odds ratio (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. Compared to past users, current CCB users had significant reductions in risks of CV events [OR 0.88 (95% CI: 0.84-0.91)], hospitalization [0.90 (0.88-0.93)] and mortality [0.48 (0.47-0.49)]. Current users of long-acting dihydropyridines (DHPs) had the lowest risk [OR 0.87 (0.84-0.90), 0.86 (0.83-0.90), 0.55 (0.54-0.56) for acute CV events, hospitalizations and mortality], whereas current users of short-acting CCBs had an increased risk of acute CV events [OR 1.77 (1.13-2.78) for short-acting DHPs; 1.19 (1.07-1.31) for short-acting non-DHPs] and hospitalizations [OR 1.84 (0.96-3.51) and 1.23 (1.08-1.42)]. The already-existing warning on short-acting CCBs should be potentiated, addressing clinicians towards the choice of long-acting formulations.

  19. The impact of the catechol-O-methyltransferase genotype on vascular function and blood pressure after acute green tea ingestion.

    PubMed

    Miller, Rosalind J; Jackson, Kim G; Dadd, Tony; Mayes, Andrew E; Brown, A Louise; Lovegrove, Julie A; Minihane, Anne M

    2012-06-01

    Evidence for the benefits of green tea catechins on vascular function is inconsistent, with genotype potentially contributing to the heterogeneity in response. Here, the impact of the catechol-O-methyltransferase (COMT) genotype on vascular function and blood pressure (BP) after green tea extract ingestion are reported. Fifty subjects (n = 25 of the proposed low-activity [AA] and of the high-activity [GG] COMT rs4680 genotype), completed a randomized, double-blind, crossover study. Peripheral arterial tonometry, digital volume pulse (DVP), and BP were assessed at baseline and 90 min after 1.06 g of green tea extract or placebo. A 5.5 h and subsequent 18.5 h urine collection was performed to assess green tea catechin excretion. A genotype × treatment interaction was observed for DVP reflection index (p = 0.014), with green tea extract in the AA COMT group attenuating the increase observed with placebo. A tendency for a greater increase in diastolic BP was evident at 90 min after the green tea extract compared to placebo (p = 0.07). A genotypic effect was observed for urinary methylated epigallocatechin during the first 5.5 h, with the GG COMT group demonstrating a greater concentration (p = 0.049). Differences in small vessel tone according to COMT genotype were evident after acute green tea extract. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Assessment of tumor response to radiation and vascular targeting therapy in mice using quantitative ultrasound spectroscopy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    El Kaffas, Ahmed; Sadeghi-Naini, Ali; Falou, Omar

    Purpose: It is now recognized that the tumor vasculature is in part responsible for regulating tumor responses to radiation therapy. However, the extent to which radiation-based vascular damage contributes to tumor cell death remains unknown. In this work, quantitative ultrasound spectroscopy (QUS) methods were used to investigate the acute responses of tumors to radiation-based vascular treatments. Methods: Tumor xenografts (MDA-MB-231) were treated with single radiation doses of 2 or 8 Gy alone, or in combination with pharmacological agents that modulate vascular radiosensitivity. The midband fit, the slope, and the 0-MHz intercept QUS parameters were obtained from a linear-regression fit tomore » the averaged power spectrum of frequency-dependent ultrasound backscatter and were used to quantify acute tumor responses following treatment administration. Power spectrums were extracted from raw volumetric radio-frequency ultrasound data obtained before and 24 h following treatment administration. These parameters have previously been correlated to tumor cell death. Staining using in situ end labeling, carbonic anhydrase 9 and cluster of differentiation 31 of tumor sections were used to assess cell death, oxygenation, and vasculature distributions, respectively. Results: Results indicate a significant midband fit QUS parameter increases of 3.2 ± 0.3 dBr and 5.4 ± 0.5 dBr for tumors treated with 2 and 8 Gy radiation combined with the antiangiogenic agent Sunitinib, respectively. In contrast, tumors treated with radiation alone demonstrated a significant midband fit increase of 4.4 ± 0.3 dBr at 8 Gy only. Preadministration of basic fibroblast growth factor, an endothelial radioprotector, acted to minimize tumor response following single large doses of radiation. Immunohistochemical analysis was in general agreement with QUS findings; an R{sup 2} of 0.9 was observed when quantified cell death was correlated with changes in midband fit. Conclusions: Results from QUS

  1. Association of vascular fluoride uptake with vascular calcification and coronary artery disease.

    PubMed

    Li, Yuxin; Berenji, Gholam R; Shaba, Wisam F; Tafti, Bashir; Yevdayev, Ella; Dadparvar, Simin

    2012-01-01

    The feasibility of a fluoride positron emission tomography/computed tomography (PET/CT) scan for imaging atherosclerosis has not been well documented. The purpose of this study was to assess fluoride uptake of vascular calcification in various major arteries, including coronary arteries. We retrospectively reviewed the imaging data and cardiovascular history of 61 patients who received whole-body sodium [¹⁸F]fluoride PET/CT studies at our institution from 2009 to 2010. Fluoride uptake and calcification in major arteries, including coronary arteries, were analyzed by both visual assessment and standardized uptake value measurement. Fluoride uptake in vascular walls was demonstrated in 361 sites of 54 (96%) patients, whereas calcification was observed in 317 sites of 49 (88%) patients. Significant correlation between fluoride uptake and calcification was observed in most of the arterial walls, except in those of the abdominal aorta. Fluoride uptake in coronary arteries was demonstrated in 28 (46%) patients and coronary calcifications were observed in 34 (56%) patients. There was significant correlation between history of cardiovascular events and presence of fluoride uptake in coronary arteries. The coronary fluoride uptake value in patients with cardiovascular events was significantly higher than in patients without cardiovascular events. sodium [¹⁸F]fluoride PET/CT might be useful in the evaluation of the atherosclerotic process in major arteries, including coronary arteries. An increased fluoride uptake in coronary arteries may be associated with an increased cardiovascular risk.

  2. Clinical Risk Factors for In-Hospital Adverse Cardiovascular Events After Acute Drug Overdose

    PubMed Central

    Manini, Alex F.; Hoffman, Robert S.; Stimmel, Barry; Vlahov, David

    2015-01-01

    Objectives It was recently demonstrated that adverse cardiovascular events (ACVE) complicate a high proportion of hospitalizations for patients with acute drug overdoses. The aim of this study was to derive independent clinical risk factors for ACVE in patients with acute drug overdoses. Methods This prospective cohort study was conducted over 3 years at two urban university hospitals. Patients were adults with acute drug overdoses enrolled from the ED. In-hospital ACVE was defined as any of myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest. Results There were 1,562 patients meeting inclusion/exclusion criteria (mean age, 41.8 years; female, 46%; suicidal, 38%). ACVE occurred in 82 (5.7%) patients (myocardial injury, 61; shock, 37; dysrhythmia, 23; cardiac arrests, 22) and there were 18 (1.2%) deaths. On univariate analysis, ACVE risk increased with age, lower serum bicarbonate, prolonged QTc interval, prior cardiac disease, and altered mental status. In a multivariable model adjusting for these factors as well as patient sex and hospital site, independent predictors were: QTc > 500 msec (3.8% prevalence, odds ratio [OR] 27.6), bicarbonate < 20 mEql/L (5.4% prevalence, OR 4.4), and prior cardiac disease (7.1% prevalence, OR 9.5). The derived prediction rule had 51.6% sensitivity, 93.7% specificity, and 97.1% negative predictive value; while presence of two or more risk factors had 90.9% positive predictive value. Conclusions The authors derived independent clinical risk factors for ACVE in patients with acute drug overdose, which should be validated in future studies as a prediction rule in distinct patient populations and clinical settings. PMID:25903997

  3. Gastric Necrosis due to Acute Massive Gastric Dilatation.

    PubMed

    Aydin, Ibrahim; Pergel, Ahmet; Yucel, Ahmet Fikret; Sahin, Dursun Ali; Ozer, Ender

    2013-01-01

    Gastric necrosis due to acute massive gastric dilatation is relatively rare. Vascular reasons, herniation, volvulus, acute gastric dilatation, anorexia, and bulimia nervosa play a role in the etiology of the disease. Early diagnosis and treatment are highly important as the associated morbidity and mortality rates are high. In this case report, we present a case of gastric necrosis due to acute gastric dilatation accompanied with the relevant literature.

  4. Gastric Necrosis due to Acute Massive Gastric Dilatation

    PubMed Central

    Pergel, Ahmet; Yucel, Ahmet Fikret; Sahin, Dursun Ali; Ozer, Ender

    2013-01-01

    Gastric necrosis due to acute massive gastric dilatation is relatively rare. Vascular reasons, herniation, volvulus, acute gastric dilatation, anorexia, and bulimia nervosa play a role in the etiology of the disease. Early diagnosis and treatment are highly important as the associated morbidity and mortality rates are high. In this case report, we present a case of gastric necrosis due to acute gastric dilatation accompanied with the relevant literature. PMID:23983714

  5. Factors associated with emergency medical services scope of practice for acute cardiovascular events.

    PubMed

    Williams, Ishmael; Valderrama, Amy L; Bolton, Patricia; Greek, April; Greer, Sophia; Patterson, Davis G; Zhang, Zefeng

    2012-01-01

    To examine prehospital emergency medical services (EMS) scope of practice for acute cardiovascular events and characteristics that may affect scope of practice; and to describe variations in EMS scope of practice for these events and the characteristics associated with that variability. In 2008, we conducted a telephone survey of 1,939 eligible EMS providers in nine states to measure EMS agency characteristics, medical director involvement, and 18 interventions authorized for prehospital care of acute cardiovascular events by three levels of emergency medical technician (EMT) personnel. A total of 1,292 providers responded to the survey, for a response rate of 67%. EMS scope of practice interventions varied by EMT personnel level, with the proportion of authorized interventions increasing as expected from EMT-Basic to EMT-Paramedic. Seven of eight statistically significant associations indicated that EMS agencies in urban settings were less likely to authorize interventions (odds ratios <0.7) for any level of EMS personnel. Based on the subset of six statistically significant associations, fire department-based EMS agencies were two to three times more likely to authorize interventions for EMT-Intermediate personnel. Volunteer EMS agencies were more than twice as likely as nonvolunteer agencies to authorize interventions for EMT-Basic and EMT-Intermediate personnel but were less likely to authorize any one of the 11 interventions for EMT-Paramedics. Greater medical director involvement was associated with greater likelihood of authorization of seven of the 18 interventions for EMT-Basic and EMT-Paramedic personnel but had no association with EMT-Intermediate personnel. We noted statistically significant variations in scope of practice by rural vs. urban setting, medical director involvement, and type of EMS service (fire department-based/non-fire department-based; volunteer/paid). These variations highlight local differences in the composition and capacity of EMS

  6. VEGF signaling inside vascular endothelial cells and beyond

    PubMed Central

    Eichmann, Anne; Simons, Michael

    2014-01-01

    Vascular endothelial growth factor-A (VEGF-A) has long been recognized as the key regulator of vascular development and function in health and disease. VEGF is a secreted polypeptide that binds to transmembrane tyrosine kinase VEGF receptors on the plasma membrane, inducing their dimerization, activation and assembly of a membrane-proximal signaling complex. Recent studies have revealed that many key events of VEGFR signaling occur inside the endothelial cell and are regulated by endosomal receptor trafficking. Plasma membrane VEGFR interacting molecules, including vascular guidance receptors Neuropilins and Ephrins also regulate VEGFR endocytosis and trafficking. VEGF signaling is increasingly recognized for its roles outside of the vascular system, notably during neural development, and blood vessels regulate epithelial branching morphogenesis. We review here recent advances in our understanding of VEGF signaling and its biological roles. PMID:22366328

  7. Endothelial dysfunction, vascular disease and stroke: the ARTICO study.

    PubMed

    Roquer, J; Segura, T; Serena, J; Castillo, J

    2009-01-01

    Endothelial dysfunction is a fundamental step in the atherosclerotic disease process. Its presence is a risk factor for the development of clinical events, and may represent a marker of atherothrombotic burden. Also, endothelial dysfunction contributes to enhanced plaque vulnerability, may trigger plaque rupture, and favors thrombus formation. The assessment of endothelial vasomotion is a useful marker of atherosclerotic vascular disease. There are different methods to assess endothelial function: endothelium-dependent vasodilatation brachial flow-mediated dilation, cerebrovascular reactivity to L-arginine, and the determination of some biomarkers such as microalbuminuria, platelet function, and C-reactive protein. Endothelial dysfunction has been observed in stroke patients and has been related to stroke physiopathology, stroke subtypes, clinical severity and outcome. Resting ankle-brachial index (ABI) is also considered an indicator of generalized atherosclerosis, and a low ABI is associated with an increase in stroke incidence in the elderly. Despite all these data, there are no studies analyzing the predictive value of ABI for new cardiovascular events in patients after suffering an acute ischemic stroke. ARTICO is an ongoing prospective, observational, multicenter study being performed in 50 Spanish hospitals. The aim of the ARTICO study is to evaluate the prognostic value of a pathological ABI (event during a 1-year follow-up after first-ever ischemic stroke. Secondary objectives include the evaluation of the predictive value for major cardiovascular events of the carotid intima-media thickness, carotid duplex findings, and certain biomarkers. Data from the ARTICO study will increase the knowledge of patient outcome after ischemic stroke and may help to improve our ability to detect patients at high risk of stroke recurrence or major cardiovascular events. (c) 2009 S. Karger AG, Basel.

  8. Multi-modal in vivo imaging of brain blood oxygenation, blood flow and neural calcium dynamics during acute seizures

    NASA Astrophysics Data System (ADS)

    Ringuette, Dene; Jeffrey, Melanie A.; Carlen, Peter L.; Levi, Ofer

    2016-03-01

    Dysfunction of the vascular endothelium has been implicated in the development of epilepsy. To better understand the relation between vascular function and seizure and provide a foundation for interpreting results from functional imaging in chronic disease models, we investigate the relationship between intracellular calcium dynamics and local cerebral blood flow and blood oxygen saturation during acute seizure-like events and pharmacological seizure rescue. To probe the relation between the aforementioned physiological markers in an acute model of epilepsy in rats, we integrated three different optical modalities together with electrophysiological recordings: Laser speckle contrast imaging (LSCI) was used to study changes in flow speeds, Intrinsic optical signal imaging (IOSI) was used to monitor changes in oxygenated, de-oxygenated, and total hemoglobin concentration, and Calcium-sensitive dye imaging was used to monitor intracellular calcium dynamics. We designed a dedicated cortical flow chamber to remove superficial blood and dye resulting from the injection procedure, which reduced spurious artifacts. The near infrared light used for IOSI and LSCI was delivered via a light pipe integrated with the flow chamber to minimize the effect of fluid surface movement on illumination stability. Calcium-sensitive dye was injected via a glass electrode used for recording the local field potential. Our system allowed us to observe and correlate increases in intracellular calcium, blood flow and blood volume during seizure-like events and provide a quantitative analysis of neurovascular coupling changes associated with seizure rescue via injection of an anti-convulsive agent.

  9. Monitoring pulmonary vascular permeability using radiolabeled transferrin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Basran, G.S.; Hardy, J.G.

    1988-07-01

    A simple, noninvasive technique for monitoring pulmonary vascular permeability in patients in critical care units is discussed. High vascular permeability is observed in patients with clinically defined adult respiratory distress syndrome (ARDS) but not in patients with hydrostatic pulmonary edema or in patients with minor pulmonary insults who are considered to be at risk of developing ARDS. The technique has been used in the field of therapeutics and pharmacology to test the effects of the putative antipermeability agents methylprednisolone and terbutaline sulfate. There appears to be a good correlation between the acute inhibitory effect of either drug on transferrin exudationmore » and patient prognosis. Thus, a byproduct of such drug studies may be an index of survival in patients with established ARDS.« less

  10. VESGEN Software for Mapping and Quantification of Vascular Regulators

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, Patricia A.; Vickerman, Mary B.; Keith, Patricia A.

    2012-01-01

    VESsel GENeration (VESGEN) Analysis is an automated software that maps and quantifies effects of vascular regulators on vascular morphology by analyzing important vessel parameters. Quantification parameters include vessel diameter, length, branch points, density, and fractal dimension. For vascular trees, measurements are reported as dependent functions of vessel branching generation. VESGEN maps and quantifies vascular morphological events according to fractal-based vascular branching generation. It also relies on careful imaging of branching and networked vascular form. It was developed as a plug-in for ImageJ (National Institutes of Health, USA). VESGEN uses image-processing concepts of 8-neighbor pixel connectivity, skeleton, and distance map to analyze 2D, black-and-white (binary) images of vascular trees, networks, and tree-network composites. VESGEN maps typically 5 to 12 (or more) generations of vascular branching, starting from a single parent vessel. These generations are tracked and measured for critical vascular parameters that include vessel diameter, length, density and number, and tortuosity per branching generation. The effects of vascular therapeutics and regulators on vascular morphology and branching tested in human clinical or laboratory animal experimental studies are quantified by comparing vascular parameters with control groups. VESGEN provides a user interface to both guide and allow control over the users vascular analysis process. An option is provided to select a morphological tissue type of vascular trees, network or tree-network composites, which determines the general collections of algorithms, intermediate images, and output images and measurements that will be produced.

  11. Brain Perivascular Spaces as Biomarkers of Vascular Risk: Results from the Northern Manhattan Study.

    PubMed

    Gutierrez, J; Elkind, M S V; Dong, C; Di Tullio, M; Rundek, T; Sacco, R L; Wright, C B

    2017-05-01

    Dilated perivascular spaces in the brain are associated with greater arterial pulsatility. We hypothesized that perivascular spaces identify individuals at higher risk for systemic and cerebral vascular events. Stroke-free participants in the population-based Northern Manhattan Study had brain MR imaging performed and were followed for myocardial infarction, any stroke, and death. Imaging analyses distinguished perivascular spaces from lesions presumably ischemic. Perivascular spaces were further subdivided into lesions with diameters of ≤3 mm (small perivascular spaces) and >3 mm (large perivascular spaces). We calculated relative rates of events with Poisson models and hazard ratios with Cox proportional models. The Northern Manhattan Study participants who had MR imaging data available for review ( n = 1228; 59% women, 65% Hispanic; mean age, 71 ± 9 years) were followed for an average of 9 ± 2 years. Participants in the highest tertile of the small perivascular space score had a higher relative rate of all deaths (relative rate, 1.38; 95% CI, 1.01-1.91), vascular death (relative rate, 1.87; 95% CI, 1.12-3.14), myocardial infarction (relative rate, 2.08; 95% CI, 1.01-4.31), any stroke (relative rate, 1.79; 95% CI, 1.03-3.11), and any vascular event (relative rate, 1.74; 95% CI, 1.18-2.56). After we adjusted for confounders, there was a higher risk of vascular death (hazard ratio, 1.06; 95% CI, 1.01-1.11), myocardial infarction (hazard ratio, 2.22; 95% CI, 1.12-4.42), and any vascular event (hazard ratio, 1.04; 95% CI, 1.01-1.08) with higher small perivascular space scores. In this multiethnic, population-based study, participants with a high burden of small perivascular spaces had increased risk of vascular events. By gaining pathophysiologic insight into the mechanism of perivascular space dilation, we may be able to propose novel therapies to better prevent vascular disorders in the population. © 2017 by American Journal of Neuroradiology.

  12. Acute cardiac events and deployment of emergency medical teams and automated external defibrillators in large football stadiums in the Netherlands.

    PubMed

    van de Sandt, Femke; Umans, Victor

    2009-10-01

    The incidence of acute cardiac events - including out-of-hospital cardiac arrest - may be increased in visitors of large sports stadiums when compared with the general population. This study sought to investigate the incidence of acute cardiac events inside large Dutch football stadiums, as well as the emergency response systems deployed in these stadiums and the success rate for in-stadium resuscitation. Retrospective cohort study using a questionnaire sent to the 20 Dutch stadiums that hosted professional matches during the 2006-2007 and 2007-2008 football seasons. Stadium capacity ranged from 3600 to 51 600 spectators. Nearly 13 million spectators attended 686 'Eredivisie' (Honorary Division) and European football matches. All stadiums distribute multiple emergency medical teams among the spectators. Eighty-five percent of the stadiums have an ambulance standby during matches, 95% of the stadiums were equipped with automated external defibrillators (AEDs) during the study period. On an average, one AED was available for every 7576 spectators (range 1800-29 600). Ninety-three cardiac events were reported (7.3 per 1 million spectators). An AED was used 22 times (1.7 per 1 million spectators). Resuscitation was successful in 18 cases (82%, 95% confidence interval: 61-93). The incidence of out-of-hospital cardiac arrest inside large football stadiums in the Netherlands, albeit increased when compared with the general population, is low. The success rate for in-stadium resuscitation by medical teams equipped with AEDs is high. Dutch stadiums appear vigilant in regard to acute cardiac events. This report highlights the importance of adequate emergency medical response systems (including AEDs) in large sports venues.

  13. The clinical usefulness of extravascular lung water and pulmonary vascular permeability index to diagnose and characterize pulmonary edema: a prospective multicenter study on the quantitative differential diagnostic definition for acute lung injury/acute respiratory distress syndrome

    PubMed Central

    2012-01-01

    Introduction Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria. Methods The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO2/FiO2 ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy. Results Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P < 0.01). PVPI was higher in ALI/ARDS patients than in cardiogenic edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P < 0.01). In ALI/ARDS patients, EVLWI increased with increasing pulmonary vascular permeability (r = 0.729, P < 0.01) and was weakly

  14. Central diabetes insipidus in children with acute brain insult.

    PubMed

    Yang, Yun-Hsuan; Lin, Jainn-Jim; Hsia, Shao-Hsuan; Wu, Chang-Teng; Wang, Huei-Shyong; Hung, Po-Cheng; Chou, Min-Liang; Hsieh, Meng-Ying; Lin, Kuang-Lin

    2011-12-01

    Central diabetes insipidus occurs in patients with overwhelming central nervous system injuries, and may be associated with brain death. The clinical picture of children with acquired central diabetes insipidus after acute brain insult is seldom reported. We retrospectively reviewed cases dating from January 2000-February 2008 at a tertiary pediatric intensive care unit. Fifty-four patients (28 girls, 26 boys), aged 3 months to 18 years, were enrolled. Etiologies included severe central nervous system infection (35.2%), hypoxic-ischemic events (31.5%), head injury (18.5%), and vascular lesions (14.8%). In 39 (72.2%) patients, diabetes insipidus was diagnosed during the first 2 days after acute central nervous system injury, and 40 (74.0%) developed maximum serum sodium concentrations of >160 mEq/L. In 16, sequential cerebral salt wasting syndrome developed after their initial diabetes insipidus presentation. Overall mortality at 2 months after admission was 77.8%. Our results demonstrate that patients who develop central diabetes insipidus after acute central nervous system injury manifest high mortality. Development of central diabetes insipidus within the first 2 days and a maximum plasma sodium >160 mEq/L were significant predictors of outcomes. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Statin withdrawal: clinical implications and molecular mechanisms.

    PubMed

    Cubeddu, Luigi X; Seamon, Matthew J

    2006-09-01

    Retrospective analyses of data from the Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM), the National Registry of Myocardial Infarction 4, and the Global Registry of Acute Coronary Events (GRACE) trials revealed that the benefits of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) on acute coronary outcomes are rapidly lost and outcomes worsened if statins are discontinued during a patient's hospitalization for an acute coronary syndrome. Withdrawal of statin therapy in the first 24 hours of hospitalization for non-ST-elevation myocardial infarction increased the hospital morbidity and mortality rate versus continued therapy (11.9% vs 5.7%, p<0.01). Data from the Treating New Targets (TNT) study, however, suggested that short-term discontinuation of statin therapy in patients with stable cardiac conditions may not substantially increase the risk of acute coronary syndromes. In patients with acute coronary syndromes who discontinue statins, the rapid increase in risk of an event may result not only from the lost benefits from the therapy, but also from rebound inhibition of vascular protective substances and activation of vascular deleterious substances. Statins inhibit cholesterol synthesis in vascular cells. By reducing levels of isoprenoid intermediates, statins increase the production of nitric oxide and downregulate angiotensin II AT(1) receptors, endothelin-1, vascular inflammatory adhesion molecules, and inflammatory cytokines. These benefits are rapidly lost and often transiently reversed when statins are acutely discontinued. Acute removal of pleiotropic effects and rebound vascular dysfunction may be more important in an acute coronary event, where inflammation promotes rupture of atherosclerotic plaques and inflammatory and prothrombosis markers are present in high concentration, than in stable chronic vascular disease. In the absence of data from randomized controlled trials, current information suggests that

  16. Computed Tomography Imaging Features in Acute Uncomplicated Stanford Type-B Aortic Dissection Predict Late Adverse Events.

    PubMed

    Sailer, Anna M; van Kuijk, Sander M J; Nelemans, Patricia J; Chin, Anne S; Kino, Aya; Huininga, Mark; Schmidt, Johanna; Mistelbauer, Gabriel; Bäumler, Kathrin; Chiu, Peter; Fischbein, Michael P; Dake, Michael D; Miller, D Craig; Schurink, Geert Willem H; Fleischmann, Dominik

    2017-04-01

    Medical treatment of initially uncomplicated acute Stanford type-B aortic dissection is associated with a high rate of late adverse events. Identification of individuals who potentially benefit from preventive endografting is highly desirable. The association of computed tomography imaging features with late adverse events was retrospectively assessed in 83 patients with acute uncomplicated Stanford type-B aortic dissection, followed over a median of 850 (interquartile range 247-1824) days. Adverse events were defined as fatal or nonfatal aortic rupture, rapid aortic growth (>10 mm/y), aneurysm formation (≥6 cm), organ or limb ischemia, or new uncontrollable hypertension or pain. Five significant predictors were identified using multivariable Cox regression analysis: connective tissue disease (hazard ratio [HR] 2.94, 95% confidence interval [CI]: 1.29-6.72; P =0.01), circumferential extent of false lumen in angular degrees (HR 1.03 per degree, 95% CI: 1.01-1.04, P =0.003), maximum aortic diameter (HR 1.10 per mm, 95% CI: 1.02-1.18, P =0.015), false lumen outflow (HR 0.999 per mL/min, 95% CI: 0.998-1.000; P =0.055), and number of intercostal arteries (HR 0.89 per n, 95% CI: 0.80-0.98; P =0.024). A prediction model was constructed to calculate patient specific risk at 1, 2, and 5 years and to stratify patients into high-, intermediate-, and low-risk groups. The model was internally validated by bootstrapping and showed good discriminatory ability with an optimism-corrected C statistic of 70.1%. Computed tomography imaging-based morphological features combined into a prediction model may be able to identify patients at high risk for late adverse events after an initially uncomplicated type-B aortic dissection. © 2017 American Heart Association, Inc.

  17. Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients With Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study.

    PubMed

    Paciaroni, Maurizio; Agnelli, Giancarlo; Caso, Valeria; Tsivgoulis, Georgios; Furie, Karen L; Tadi, Prasanna; Becattini, Cecilia; Falocci, Nicola; Zedde, Marialuisa; Abdul-Rahim, Azmil H; Lees, Kennedy R; Alberti, Andrea; Venti, Michele; Acciarresi, Monica; D'Amore, Cataldo; Mosconi, Maria Giulia; Cimini, Ludovica Anna; Procopio, Antonio; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Cappellari, Manuel; Putaala, Jukka; Tomppo, Liisa; Tatlisumak, Turgut; Bandini, Fabio; Marcheselli, Simona; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Masotti, Luca; Vannucchi, Vieri; Sohn, Sung-Il; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Acampa, Maurizio; Martini, Giuseppe; Ntaios, George; Karagkiozi, Efstathia; Athanasakis, George; Makaritsis, Kostantinos; Vadikolias, Kostantinos; Liantinioti, Chrysoula; Chondrogianni, Maria; Mumoli, Nicola; Consoli, Domenico; Galati, Franco; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Corea, Francesco; Ageno, Walter; Bellesini, Marta; Colombo, Giovanna; Silvestrelli, Giorgio; Ciccone, Alfonso; Scoditti, Umberto; Denti, Licia; Mancuso, Michelangelo; Maccarrone, Miriam; Orlandi, Giovanni; Giannini, Nicola; Gialdini, Gino; Tassinari, Tiziana; De Lodovici, Maria Luisa; Bono, Giorgio; Rueckert, Christina; Baldi, Antonio; D'Anna, Sebastiano; Toni, Danilo; Letteri, Federica; Giuntini, Martina; Lotti, Enrico Maria; Flomin, Yuriy; Pieroni, Alessio; Kargiotis, Odysseas; Karapanayiotides, Theodore; Monaco, Serena; Baronello, Mario Maimone; Csiba, Laszló; Szabó, Lilla; Chiti, Alberto; Giorli, Elisa; Del Sette, Massimo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Michel, Patrik; Vanacker, Peter; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Gourbali, Vanessa; Yaghi, Shadi

    2017-03-01

    This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P =0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P =0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P =0.10) for major bleedings. The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P =0.009) for ischemic outcome events and 0.407 (0.275-0.540; P =0.14) for hemorrhagic outcome events. In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings. © 2017 American Heart Association, Inc.

  18. Evaluation of Clinical Outcomes and Renal Vascular Pathology among Patients with Lupus

    PubMed Central

    Barber, Claire; Herzenberg, Andrew; Aghdassi, Ellie; Su, Jiandong; Lou, Wendy; Qian, Gan; Yip, Jonathan; Nasr, Samih H.; Thomas, David; Scholey, James W.; Wither, Joan; Urowitz, Murray; Gladman, Dafna; Reich, Heather

    2012-01-01

    Summary Background and objectives The objective of this study was to determine the clinical significance of renal vascular lesions in lupus nephritis. Design, setting, participants, & measurements Renal vascular lesions defined as thrombotic microangiopathy, lupus vasculopathy, uncomplicated vascular immune deposits, and arterial sclerosis were evaluated in relation to renal and vascular morbidity and overall mortality. Results Biopsies from 161 patients revealed thrombotic microangiopathy (13), lupus vasculopathy (5), and arterial sclerosis (93). No renal vascular lesions were found in 24.8% of patients. At the time of biopsy, arterial sclerosis or lupus vasculopathy patients were older (arterial sclerosis=37.9±13.0 and lupus vasculopathy=44.4±8.9 versus controls=33.1±8.9 years, P<0.05), and the mean arterial pressure was higher in all groups compared with controls. Nephritis subtype, activity indices, and proteinuria were similar between groups, estimated GFR was lower in arterial sclerosis (70.5±33.3 versus 84.5±26.6 ml/min per 1.73 m2, P=0.03), and chronicity index (thrombotic microangiopathy=3.5, lupus vasculopathy=4.5, and arterial sclerosis=2.5) was higher in all renal vascular lesions subgroups versus controls (1.0, P<0.05). In 133 patients with similar follow-up, the association between renal vascular lesions and vascular events was significant (Fisher exact test, P=0.002) and remained so after multivariate analysis (exact conditional scores test, P=0.04), where the difference between arterial sclerosis and uncomplicated vascular immune deposits was most noticeable (odds ratio [95% confidence interval]=8.35[0.98, 83.12], P=0.05). The associations between renal vascular lesions, renal outcomes, and death were not significant, likely because of insufficient power. Conclusions Renal vascular lesions are common in SLE patients with nephritis and may be associated with arterial vascular events. PMID:22442181

  19. Genetic and epigenetic mechanisms in the early development of the vascular system

    PubMed Central

    Ribatti, Domenico

    2006-01-01

    The cardiovascular system plays a critical role in vertebrate development and homeostasis. Vascular development is a highly organized sequence of events that requires the correct spatial and temporal expression of specific sets of genes leading to the development of a primary vascular network. There have been intensive efforts to determine the molecular mechanisms regulating vascular growth and development, and much of the rationale for this has stemmed from the increasing clinical importance and therapeutic potential of modulating vascular formation during various disease states. PMID:16441559

  20. Nitric oxide (NO) in normal and hypoxic vascular regulation of the spiny dogfish, Squalus acanthias.

    PubMed

    Swenson, Kai E; Eveland, Randy L; Gladwin, Mark T; Swenson, Erik R

    2005-02-01

    Nitric oxide (NO) is a potent vasodilator in terrestrial vertebrates, but whether vascular endothelial-derived NO plays a role in vascular regulation in fish remains controversial. To explore this issue, a study was made of spiny dogfish sharks (Squalus acanthias) in normoxia and acute hypoxia (60 min exposure to seawater equilibrated with 3% oxygen) with various agents known to alter NO metabolism or availability. In normoxia, nitroprusside (a NO donor) reduced blood pressure by 20%, establishing that vascular smooth muscle responds to NO. L-arginine, the substrate for NO synthase, had no hemodynamic effect. Acetylcholine, which stimulates endothelial NO and prostaglandin production in mammals, reduced blood pressure, but also caused marked bradycardia. L-NAME, an inhibitor of all NO synthases, caused a small 10% rise in blood pressure, but cell-free hemoglobin (a potent NO scavenger and hypertensive agent in mammals) had no effect. Acute hypoxia caused a 15% fall in blood pressure, which was blocked by L-NAME and cell-free hemoglobin. Serum nitrite, a marker of NO production, rose with hypoxia, but not with L-NAME. Results suggest that NO is not an endothelial-derived vasodilator in the normoxic elasmobranch. The hypertensive effect of L-NAME may represent inhibition of NO production in the CNS and nerves regulating blood pressure. In acute hypoxia, there is a rapid up-regulation of vascular NO production that appears to be responsible for hypoxic vasodilation.

  1. The Oxidized Low-Density Lipoprotein Receptor Mediates Vascular Effects of Inhaled Vehicle Emissions

    PubMed Central

    Lucero, JoAnn; Harman, Melissa; Madden, Michael C.; McDonald, Jacob D.; Seagrave, Jean Clare; Campen, Matthew J.

    2011-01-01

    Rationale: To determine vascular signaling pathways involved in inhaled air pollution (vehicular engine emission) exposure–induced exacerbation of atherosclerosis that are associated with onset of clinical cardiovascular events. Objectives: To elucidate the role of oxidized low-density lipoprotein (oxLDL) and its primary receptor on endothelial cells, the lectin-like oxLDL receptor (LOX-1), in regulation of endothelin-1 expression and matrix metalloproteinase activity associated with inhalational exposure to vehicular engine emissions. Methods: Atherosclerotic apolipoprotein E knockout mice were exposed by inhalation to filtered air or mixed whole engine emissions (250 μg particulate matter [PM]/m3 diesel + 50 μg PM/m3 gasoline exhausts) 6 h/d for 7 days. Concurrently, mice were treated with either mouse IgG or neutralizing antibodies to LOX-1 every other day. Vascular and plasma markers of oxidative stress and expression proatherogenic factors were assessed. In a parallel study, healthy human subjects were exposed to either 100 μg PM/m3 diesel whole exhaust or high-efficiency particulate air and charcoal-filtered “clean” air (control subjects) for 2 hours, on separate occasions. Measurements and Main Results: Mixed emissions exposure increased oxLDL and vascular reactive oxygen species, as well as LOX-1, matrix metalloproteinase-9, and endothelin-1 mRNA expression and also monocyte/macrophage infiltration, each of which was attenuated with LOX-1 antibody treatment. In a parallel study, diesel exhaust exposure in volunteer human subjects induced significant increases in plasma-soluble LOX-1. Conclusions: These findings demonstrate that acute exposure to vehicular source pollutants results in up-regulation of vascular factors associated with progression of atherosclerosis, endothelin-1, and matrix metalloproteinase-9, mediated through oxLDL–LOX-1 receptor signaling, which may serve as a novel target for future therapy. PMID:21493736

  2. [Bone metabolism and cardiovascular function Update. Vascular calcification as a manifestation of bone-vascular axis].

    PubMed

    Kurabayashi, Masahiko

    2014-07-01

    Vascular calcification is the major cause of cardiovascular morbidity and mortality in the patients with type 2 diabetes, chronic kidney disease and in aging patients. Regardless of the morphology and location, most evidence indicates that vascular calcification involves an organized process recapitulating many cellular and molecular events that govern skeletal bone formation. While the large body of evidence that osteoblastic and osteochondrocytic cells contribute to vascular calcification, it remains unclear how osteoclasts are differentiated from their precursors and how osteoclasts play a role in calcium reabsorption in calcifying arteries. It is reassuring that calcium paradox is not merely due to the calcium shift from bone to artery wall, but is likely due to the differential response of both osteoblasts and osteoclasts to oxidative stress between bone and artery. To date, many studies have highlighted the important role for RANK/RANKL/OPG axis as unifying theme for the apparently opposite regulation of calcification between two tissues.

  3. A score including ADAM17 substrates correlates to recurring cardiovascular event in subjects with atherosclerosis.

    PubMed

    Rizza, Stefano; Copetti, Massimiliano; Cardellini, Marina; Menghini, Rossella; Pecchioli, Chiara; Luzi, Alessio; Di Cola, Giovanni; Porzio, Ottavia; Ippoliti, Arnaldo; Romeo, Franco; Pellegrini, Fabio; Federici, Massimo

    2015-04-01

    Atherosclerosis disease is a leading cause for mortality and morbidity. The narrowing/rupture of a vulnerable atherosclerotic plaque is accountable for acute cardiovascular events. However, despite of an intensive research, a reliable clinical method which may disclose a vulnerable patient is still unavailable. We tested the association of ADAM17 (A Disintegrin and Metallo Protease Domain 17) circulating substrates (sICAM-1, sVCAM-1, sIL6R and sTNFR1) with a second major cardiovascular events [MACEs] (cardiovascular death, peripheral artery surgeries, non-fatal myocardial infarction and non-fatal stroke) in 298 patients belonging to the Vascular Diabetes (AVD) study. To evaluate ADAM17 activity we create ADAM17 score through a RECPAM model. Finally we tested the discrimination ability and the reclassification of clinical models. At follow-up (mean 47 months, range 1-118 months), 55 MACEs occurred (14 nonfatal MI, 14 nonfatal strokes, 17 peripheral artery procedures and 10 cardiovascular deaths) (incidence = 7.8% person-years). An increased risk for incident events was observed among the high ADAM17 score individuals both in univariable (HR 19.20, 95% CI 15.82-63.36, p < 0.001) and multivariable analysis (HR 3.42, 95% CI 1.55-7.54, p < 0.001). Finally we found that ADAM17 score significantly increases the prediction accuracy of the Framingham Recurring-Coronary-Heart-Disease-Score, with a significant improvement in discrimination (integrated discrimination improvement = 9%, p = 0.012) and correctly reclassifying 10% of events and 41% of non-events resulting in a cNRI = 0.51 (p = 0.005). We demonstrated a positive role of ADAM17 activity to predicting CV events. We think that an approach that targets strategies beyond classic cardiovascular risk factors control is necessary in individuals with an established vascular atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Intervention Associated Acute Kidney Injury and Long-Term Cardiovascular Outcomes.

    PubMed

    Saratzis, Athanasios; Harrison, Seamus; Barratt, Jonathan; Sayers, Robert D; Sarafidis, Pantelis A; Bown, Matthew J

    2015-01-01

    Acute kidney injury (AKI) has been associated with all-cause short- and long-term mortality. However, its association with cardiovascular (CV) events remains unclear. We sought to investigate this in patients undergoing open (OAR) or endovascular (EVAR) abdominal aortic aneurysm repair, as they are likely to develop both AKI and CV morbidity. A meta-analysis was subsequently performed to confirm this in other CV-interventions. AKI-incidence was assessed in a multicentre-cohort of 1,068 patients undergoing EVAR (947 individuals) or OAR electively using the 'Acute Kidney Injury Network' criteria. A composite-endpoint was used, consisting of non-fatal myocardial infarction (MI), stroke, vascular event, hospitalisation due to heart failure and CV death. A systematic literature review identified studies reporting AKI-incidence and CV events. Risk ratios (RRs) at 1 and 5 years were combined using meta-analysis. During a median follow-up of 62 months (range 11-121), AKI was associated with CV events on adjusted (for CV risk-factors) analyses (Incidence 36% of EVAR, 32% of OAR patients; hazard ratio 1.73, 95% CI 1.06-3.39, p=0.03) for the overall population. In the meta-analysis, 7 studies reported incidence of MI on 23,936 patients 1-year after coronary intervention (PCI) with a pooled RR of 1.76 (95% CI 1.45-2.83, p<0.001); at 2 years, 3 studies reported MI incidence on 17,773 patients after PCI with a pooled RR of 1.34 (95% CI 1.10-1.63, p=0.003). MI-incidence was reported 5 years after cardiac surgery by 3 studies (33,701 patients) with a pooled RR of 1.60 (95% CI 1.43-1.81). AKI is associated with long-term CV events after surgery or endovascular intervention. © 2015 S. Karger AG, Basel.

  5. Acute cellular rejection with isolated v-lesions is not associated with more favorable outcomes than vascular rejection with more tubulointerstitial inflammations.

    PubMed

    Wu, K Y; Budde, K; Schmidt, D; Neumayer, H H; Rudolph, B

    2014-04-01

    The impact of isolated v-lesions on clinical outcome in biopsies with acute cellular rejection (ACR) is unclear. Two hundred and sixty-five biopsies showing the highest ACR severity for each patient were recruited and classified into four groups: (i) acute interstitial rejection (AIR) I with minimal tubulointerstitial inflammation (TI), (ii) AIR II with intensive TI, (iii) acute vascular rejection (AVR) I with minimal TI, and (iv) AVR II with intensive TI. The complete reversal rates of AIR I and AIR II groups were marginally higher than AVR I and AVR II groups (p = 0.16). At eight yr of transplantation, the death-censored graft survival (DCGS) rate of AIR I group (93.3%) was significantly higher compared with the AVR I (72.7%) or AVR II (72.9%) group. AVR I group had a similar DCGS rate with AVR II group (72.7% vs. 74.1%), whereas AVR with v1-lesion showed significantly higher graft survival (GS) rate than those with v2-lesion (70.2% vs. 45.5%). The t-lesion of AIR and v-lesion of AVR group were associated with graft loss. The extent of TI is non-specifically associated with graft loss in biopsies with AVR; the higher grade v-lesion predicts the lower complete reversal rate and poorer long-term graft survival. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Acute ethanol intake induces superoxide anion generation and mitogen-activated protein kinase phosphorylation in rat aorta: A role for angiotensin type 1 receptor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yogi, Alvaro; Callera, Glaucia E.; Mecawi, André S.

    Ethanol intake is associated with increase in blood pressure, through unknown mechanisms. We hypothesized that acute ethanol intake enhances vascular oxidative stress and induces vascular dysfunction through renin–angiotensin system (RAS) activation. Ethanol (1 g/kg; p.o. gavage) effects were assessed within 30 min in male Wistar rats. The transient decrease in blood pressure induced by ethanol was not affected by the previous administration of losartan (10 mg/kg; p.o. gavage), a selective AT{sub 1} receptor antagonist. Acute ethanol intake increased plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity, plasma angiotensin I (ANG I) and angiotensin II (ANG II) levels. Ethanol inducedmore » systemic and vascular oxidative stress, evidenced by increased plasma thiobarbituric acid-reacting substances (TBARS) levels, NAD(P)H oxidase‐mediated vascular generation of superoxide anion and p47phox translocation (cytosol to membrane). These effects were prevented by losartan. Isolated aortas from ethanol-treated rats displayed increased p38MAPK and SAPK/JNK phosphorylation. Losartan inhibited ethanol-induced increase in the phosphorylation of these kinases. Ethanol intake decreased acetylcholine-induced relaxation and increased phenylephrine-induced contraction in endothelium-intact aortas. Ethanol significantly decreased plasma and aortic nitrate levels. These changes in vascular reactivity and in the end product of endogenous nitric oxide metabolism were not affected by losartan. Our study provides novel evidence that acute ethanol intake stimulates RAS activity and induces vascular oxidative stress and redox-signaling activation through AT{sub 1}-dependent mechanisms. These findings highlight the importance of RAS in acute ethanol-induced oxidative damage. -- Highlights: ► Acute ethanol intake stimulates RAS activity and vascular oxidative stress. ► RAS plays a role in acute ethanol-induced oxidative damage via AT{sub 1} receptor activation

  7. Targeting vascular (endothelial) dysfunction

    PubMed Central

    Steven, Sebastian; Weber, Alina; Shuvaev, Vladimir V.; Muzykantov, Vladimir R.; Laher, Ismail; Li, Huige; Lamas, Santiago

    2016-01-01

    Abstract Cardiovascular diseases are major contributors to global deaths and disability‐adjusted life years, with hypertension a significant risk factor for all causes of death. The endothelium that lines the inner wall of the vasculature regulates essential haemostatic functions, such as vascular tone, circulation of blood cells, inflammation and platelet activity. Endothelial dysfunction is an early predictor of atherosclerosis and future cardiovascular events. We review the prognostic value of obtaining measurements of endothelial function, the clinical techniques for its determination, the mechanisms leading to endothelial dysfunction and the therapeutic treatment of endothelial dysfunction. Since vascular oxidative stress and inflammation are major determinants of endothelial function, we have also addressed current antioxidant and anti‐inflammatory therapies. In the light of recent data that dispute the prognostic value of endothelial function in healthy human cohorts, we also discuss alternative diagnostic parameters such as vascular stiffness index and intima/media thickness ratio. We also suggest that assessing vascular function, including that of smooth muscle and even perivascular adipose tissue, may be an appropriate parameter for clinical investigations. Linked Articles This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc PMID:27187006

  8. VEGF signaling inside vascular endothelial cells and beyond.

    PubMed

    Eichmann, Anne; Simons, Michael

    2012-04-01

    Vascular endothelial growth factor-A (VEGF-A) has long been recognized as the key regulator of vascular development and function in health and disease. VEGF is a secreted polypeptide that binds to transmembrane tyrosine kinase VEGF receptors on the plasma membrane, inducing their dimerization, activation and assembly of a membrane-proximal signaling complex. Recent studies have revealed that many key events of VEGFR signaling occur inside the endothelial cell and are regulated by endosomal receptor trafficking. Plasma membrane VEGFR interacting molecules, including vascular guidance receptors Neuropilins and Ephrins also regulate VEGFR endocytosis and trafficking. VEGF signaling is increasingly recognized for its roles outside of the vascular system, notably during neural development, and blood vessels regulate epithelial branching morphogenesis. We review here recent advances in our understanding of VEGF signaling and its biological roles. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Principles for Management of Intraoperative Acute Type A Aortic Dissection.

    PubMed

    Gukop, Philemon; Chandrasekaran, Vankatachalam

    2015-12-01

    Intraoperative Type A aortic dissection is a rare pathology with incidence of 0.06-0.32%. It is associated with a high mortality between 30-50%. Some associated risk factors, including hypertension, enlarged aorta, peripheral vascular disease, advanced age, atheroma, and high arterial pressure on cardiopulmonary bypass, have been identified. Modification of these risk factors could reduce the incidence of this event. Prompt diagnosis and management, with the aid of intraoperative trans-esophageal echocardiography and/or epi-aortic ultrasound has been shown to reduce the mortality to 17%. We illustrate the principles of management of this pathology with the case of a 62-year-old female who developed acute Type A aortic dissection while undergoing minimally invasive mitral valve repair.

  10. Acute hazardous substance releases resulting in adverse health consequences in children: Hazardous Substances Emergency Events Surveillance system, 1996-2003.

    PubMed

    Wattigney, Wendy A; Kaye, Wendy E; Orr, Maureen F

    2007-11-01

    Because of their small size and ongoing organ development, children may be more susceptible than adults to the harmful effects of toxic chemicals. The objective of the study reported here was to identify frequent locations, released substances, and factors contributing to short-term chemical exposures associated with adverse health consequences experienced by children. The study examined the Hazardous Substances Emergency Events Surveillance (HSEES) system data from 1996-2003. Eligible events involved the acute release of a hazardous substance associated with at least one child being injured. The study found that injured children were predominantly at school, home, or a recreational center when events took place. School-related events were associated with the accidental release of acids and the release of pepper spray by pranksters. Carbon monoxide poisonings occurring in the home, retail stores, entertainment facilities, and hotels were responsible for about 10 percent of events involving child victims. Chlorine was one of the top chemicals harmful to children, particularly at public swimming pools. Although human error contributed to the majority of releases involving child victims, equipment failure was responsible for most chlorine and ammonia releases. The authors conclude that chemical releases resulting in injury to children occur mostly in schools, homes, and recreational areas. Surveillance of acute hazardous chemical releases helped identify contributing causes and can guide the development of prevention outreach activities. Chemical accidents cannot be entirely prevented, but efforts can be taken to provide safer environments in which children can live, learn, and play. Wide dissemination of safety recommendations and education programs is required to protect children from needless environmental dangers.

  11. Objective evaluation of acute adverse events and image quality of gadolinium-based contrast agents (gadobutrol and gadobenate dimeglumine) by blinded evaluation. Pilot study.

    PubMed

    Semelka, Richard C; Hernandes, Mateus de A; Stallings, Clifton G; Castillo, Mauricio

    2013-01-01

    The purpose was to objectively evaluate a recently FDA-approved gadolinium-based contrast agent (GBCA) in comparison to our standard GBCA for acute adverse events and image quality by blinded evaluation. Evaluation was made of a recently FDA-approved GBCA, gadobutrol (Gadavist; Bayer), in comparison to our standard GBCA, gadobenate dimeglumine (MultiHance; Bracco), in an IRB- and HIPAA-compliant study. Both the imaging technologist and patient were not aware of the brand of the GBCA used. A total of 59 magnetic resonance studies were evaluated (59 patients, 31 men, 28 women, age range of 5-85 years, mean age of 52 years). Twenty-nine studies were performed with gadobutrol (22 abdominal and 7 brain studies), and 30 studies were performed with gadobenate dimeglumine (22 abdominal and 8 brain studies). Assessment was made of acute adverse events focusing on objective observations of vomiting, hives, and moderate and severe reactions. Adequacy of enhancement was rated as poor, fair and good by one of two experienced radiologists who were blinded to the type of agent evaluated. No patient experienced acute adverse events with either agent. The target minor adverse events of vomiting or hives, and moderate and severe reactions were not observed in any patient. Adequacy of enhancement was rated as good for both agents in all patients. Objective, blinded evaluation is feasible and readily performable for the evaluation of GBCAs. This proof-of-concept study showed that both GBCAs evaluated exhibited consistent good image quality and no noteworthy adverse events. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. [An analysis of the work of vascular service in Smolensk from 2009 to 2014].

    PubMed

    Triasunova, М A; Agafonov, K I; Nehaeva, K A; Miloserdov, M A; Maslova, N N; Rakov, A M; Agulina, N A

    2015-01-01

    Report of the regional vascular service center of Smolensk work and work of vascular service of Smolensk region were analyzed. The aim of the study is to analyze work of the vascular service in Smolensk and Smolensk region in 2009-2014. Mortality and morbidity in patients with cardio-vascular diseases in Smolensk Region are higher than in other regions of Russia. Recently a number of patients hospitalized to vascular service centers are increased. Infectious complications (pneumonia, bedsores, pyoderma) take lead place in mortality. Nowadays it's very important to solve the problem with prophylaxis of infectious complications in patients with acute ischemic stroke, also to solve problem with rehabilitation in patients with mild and severe motor disorders and disorders of praxis, gnosis. Continuous training of doctors and nurses in regional vascular service centers is needed. It will increase quality of medical service and improve rehabilitation prognosis in patients with ischemic stroke.

  13. Predicting the impact of population level risk reduction in cardio-vascular disease and stroke on acute hospital admission rates over a 5 year period--a pilot study.

    PubMed

    Whitfield, Malcolm D; Gillett, Michael; Holmes, Michael; Ogden, Elaine

    2006-12-01

    The brief for this study was to produce a practical, evidence based, financial planning tool, which could be used to present an economic argument for funding a public health-based prevention programme in coronary heart disease (CHD) related illness on the same basis as treatment interventions. To explore the possibility of using multivariate risk prediction equations, derived from the Framingham and other studies, to estimate how many people in a population are likely to be admitted to hospital in the next 5-10 years with cardio vascular disease (CVD) related events such as heart attacks, strokes, heart failure and kidney disease. To estimate the potential financial impact of reductions in hospital admissions, on an 'invest to save' basis, if primary care trusts (PCTs) were to invest in public health based interventions to reduce cardiovascular risk at a population level. The populations of five UK PCTs were entered into a spreadsheet based decision tree model, in terms of age and sex (this equated to around 620,000 adults). An estimation was made to determine how many people, in each age group, were likely to be diabetic. Population risk factors such as smoking rates, mean body mass index (BMI), mean total cholesterol and mean systolic blood pressure were entered by age group. The spreadsheet then used a variant of the Framingham equation to calculate how many non-diabetic people in each age group were likely to have a heart attack or stroke in the next 5 years. In addition heart failure and dialysis admission rates were estimated based upon risk factors for incidence. The United Kingdom Prospective Diabetes Study (UKPDS) risk engines 56 and 60 were used to calculate the risk of CHD and stroke, respectively, in people with type 2 diabetes. The spreadsheet deducted the number of people likely to die before reaching hospital and produced a predicted number of hospital admissions for each category over a 5-year period. The final part of the calculation attached a

  14. Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke

    PubMed Central

    Hu, Xiaoming; De Silva, T. Michael; Chen, Jun; Faraci, Frank M.

    2017-01-01

    The consequences of cerebrovascular disease are among the leading health issues worldwide. Large and small cerebral vessel disease can trigger stroke and contribute to the vascular component of other forms of neurological dysfunction and degeneration. Both forms of vascular disease are driven by diverse risk factors, with hypertension as the leading contributor. Despite the importance of neurovascular disease and subsequent injury following ischemic events, fundamental knowledge in these areas lag behind our current understanding of neuroprotection and vascular biology in general. The goal of this review is to address select key structural and functional changes in the vasculature that promote hypoperfusion and ischemia, while also affecting the extent of injury and effectiveness of therapy. In addition, as damage to the blood-brain barrier (BBB) is one of the major consequences of ischemia, we discuss cellular and molecular mechanisms underlying ischemia-induced changes in BBB integrity and function, including alterations in endothelial cells and the contribution of pericytes, immune cells, and matrix metalloproteinases. Identification of cell types, pathways, and molecules that control vascular changes before and after ischemia may result in novel approaches to slow the progression of cerebrovascular disease and lessen both the frequency and impact of ischemic events. PMID:28154097

  15. Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke.

    PubMed

    Hu, Xiaoming; De Silva, T Michael; Chen, Jun; Faraci, Frank M

    2017-02-03

    The consequences of cerebrovascular disease are among the leading health issues worldwide. Large and small cerebral vessel disease can trigger stroke and contribute to the vascular component of other forms of neurological dysfunction and degeneration. Both forms of vascular disease are driven by diverse risk factors, with hypertension as the leading contributor. Despite the importance of neurovascular disease and subsequent injury after ischemic events, fundamental knowledge in these areas lag behind our current understanding of neuroprotection and vascular biology in general. The goal of this review is to address select key structural and functional changes in the vasculature that promote hypoperfusion and ischemia, while also affecting the extent of injury and effectiveness of therapy. In addition, as damage to the blood-brain barrier is one of the major consequences of ischemia, we discuss cellular and molecular mechanisms underlying ischemia-induced changes in blood-brain barrier integrity and function, including alterations in endothelial cells and the contribution of pericytes, immune cells, and matrix metalloproteinases. Identification of cell types, pathways, and molecules that control vascular changes before and after ischemia may result in novel approaches to slow the progression of cerebrovascular disease and lessen both the frequency and impact of ischemic events. © 2017 American Heart Association, Inc.

  16. Drugs targeting 5-hydroxytryptamine receptors in acute treatments of migraine attacks. A review of new drugs and new administration forms of established drugs.

    PubMed

    Tfelt-Hansen, Peer C; Pihl, Thomas; Hougaard, Anders; Mitsikostas, Dimos D

    2014-03-01

    The development of sumatriptan, more than 20 years ago, added substantially to the characterization of 5-hydroxytryptamine (5-HT) receptors and their relevance to acute migraine therapy. Recently, 5-HT1F receptor agonists, with no vascular effects, have shown efficacy in the treatment of migraines. This evaluation reviews the recent advances in acute migraine therapy targeting the 5-HT receptor. Specifically, the authors review the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of 5-HT1F receptor agonists and new formulations of sumatriptan and dihydroergotamine (DHE). Lasmiditan, a non-vascular acting 5-HT1F receptor agonist, is effective in migraine but causes central nervous system-related adverse events, which may considerably limit its clinical use. The efficacy of transdermal sumatriptan is too low for general use in migraine. Intranasal sumatriptan powder could be a step forward compared with oral sumatriptan, but comparative trials are needed. Orally inhaled DHE has a very quick systemic absorption but the onset of effect in migraine is relatively slow with a maximum effect after 2 h. In contrast, orally inhaled DHE results in a low incidence of recurrence. None of these reviewed treatments are likely to fulfill patients' expectations, and the advancement of acute migraine drugs should likely depend on different mechanisms from current 5-HT-related drugs.

  17. Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections.

    PubMed

    Gerber, Jeffrey S; Ross, Rachael K; Bryan, Matthew; Localio, A Russell; Szymczak, Julia E; Wasserman, Richard; Barkman, Darlene; Odeniyi, Folasade; Conaboy, Kathryn; Bell, Louis; Zaoutis, Theoklis E; Fiks, Alexander G

    2017-12-19

    Acute respiratory tract infections account for the majority of antibiotic exposure in children, and broad-spectrum antibiotic prescribing for acute respiratory tract infections is increasing. It is not clear whether broad-spectrum treatment is associated with improved outcomes compared with narrow-spectrum treatment. To compare the effectiveness of broad-spectrum and narrow-spectrum antibiotic treatment for acute respiratory tract infections in children. A retrospective cohort study assessing clinical outcomes and a prospective cohort study assessing patient-centered outcomes of children between the ages of 6 months and 12 years diagnosed with an acute respiratory tract infection and prescribed an oral antibiotic between January 2015 and April 2016 in a network of 31 pediatric primary care practices in Pennsylvania and New Jersey. Stratified and propensity score-matched analyses to account for confounding by clinician and by patient-level characteristics, respectively, were implemented for both cohorts. Broad-spectrum antibiotics vs narrow-spectrum antibiotics. In the retrospective cohort, the primary outcomes were treatment failure and adverse events 14 days after diagnosis. In the prospective cohort, the primary outcomes were quality of life, other patient-centered outcomes, and patient-reported adverse events. Of 30 159 children in the retrospective cohort (19 179 with acute otitis media; 6746, group A streptococcal pharyngitis; and 4234, acute sinusitis), 4307 (14%) were prescribed broad-spectrum antibiotics including amoxicillin-clavulanate, cephalosporins, and macrolides. Broad-spectrum treatment was not associated with a lower rate of treatment failure (3.4% for broad-spectrum antibiotics vs 3.1% for narrow-spectrum antibiotics; risk difference for full matched analysis, 0.3% [95% CI, -0.4% to 0.9%]). Of 2472 children enrolled in the prospective cohort (1100 with acute otitis media; 705, group A streptococcal pharyngitis; and 667, acute sinusitis), 868

  18. Acute Cardiovascular Events after Herpes Zoster: A Self-Controlled Case Series Analysis in Vaccinated and Unvaccinated Older Residents of the United States.

    PubMed

    Minassian, Caroline; Thomas, Sara L; Smeeth, Liam; Douglas, Ian; Brauer, Ruth; Langan, Sinéad M

    2015-12-01

    Herpes zoster is common and can have serious consequences. Additionally, emerging data suggest an increased risk of acute cardiovascular events following herpes zoster. However, to our knowledge, existing association studies compare outcomes between individuals and are therefore vulnerable to between-person confounding. In this study, we used a within-person study design to quantify any short-term increased risk of acute cardiovascular events (stroke and myocardial infarction [MI]) after zoster and to assess whether zoster vaccination modifies this association. The self-controlled case series method was used to estimate rates of stroke and acute MI in defined periods after herpes zoster compared to other time periods, within individuals. Participants were fully eligible Medicare beneficiaries aged ≥ 65 y with a herpes zoster diagnosis and either an ischemic stroke (n = 42,954) or MI (n = 24,237) between 1 January 2006 and 31 December 2011. Age-adjusted incidence ratios (IRs) for stroke and MI during predefined periods up to 12 mo after zoster relative to unexposed time periods were calculated using conditional Poisson regression. We observed a marked increase in the rate of acute cardiovascular events in the first week after zoster diagnosis: a 2.4-fold increased ischemic stroke rate (IR 2.37, 95% CI 2.17-2.59) and a 1.7-fold increased MI rate (IR 1.68, 95% CI 1.47-1.92), followed by a gradual resolution over 6 mo. Zoster vaccination did not appear to modify the association with MI (interaction p-value = 0.44). We also found no evidence for a difference in the IR for ischemic stroke between vaccinated (IR 1.14, 95% CI 0.75-1.74) and unvaccinated (IR 1.78, 95% CI 1.68-1.88) individuals during the first 4 wk after zoster diagnosis (interaction p-value = 0.28). The relatively few vaccinated individuals limited the study's power to assess the role of vaccination. Stroke and MI rates are transiently increased after exposure to herpes zoster. We found no evidence for a

  19. Acute Cardiovascular Events after Herpes Zoster: A Self-Controlled Case Series Analysis in Vaccinated and Unvaccinated Older Residents of the United States

    PubMed Central

    Minassian, Caroline; Thomas, Sara L.; Smeeth, Liam; Douglas, Ian; Brauer, Ruth; Langan, Sinéad M.

    2015-01-01

    Background Herpes zoster is common and can have serious consequences. Additionally, emerging data suggest an increased risk of acute cardiovascular events following herpes zoster. However, to our knowledge, existing association studies compare outcomes between individuals and are therefore vulnerable to between-person confounding. In this study, we used a within-person study design to quantify any short-term increased risk of acute cardiovascular events (stroke and myocardial infarction [MI]) after zoster and to assess whether zoster vaccination modifies this association. Methods and Findings The self-controlled case series method was used to estimate rates of stroke and acute MI in defined periods after herpes zoster compared to other time periods, within individuals. Participants were fully eligible Medicare beneficiaries aged ≥65 y with a herpes zoster diagnosis and either an ischemic stroke (n = 42,954) or MI (n = 24,237) between 1 January 2006 and 31 December 2011. Age-adjusted incidence ratios (IRs) for stroke and MI during predefined periods up to 12 mo after zoster relative to unexposed time periods were calculated using conditional Poisson regression. We observed a marked increase in the rate of acute cardiovascular events in the first week after zoster diagnosis: a 2.4-fold increased ischemic stroke rate (IR 2.37, 95% CI 2.17–2.59) and a 1.7-fold increased MI rate (IR 1.68, 95% CI 1.47–1.92), followed by a gradual resolution over 6 mo. Zoster vaccination did not appear to modify the association with MI (interaction p-value = 0.44). We also found no evidence for a difference in the IR for ischemic stroke between vaccinated (IR 1.14, 95% CI 0.75–1.74) and unvaccinated (IR 1.78, 95% CI 1.68–1.88) individuals during the first 4 wk after zoster diagnosis (interaction p-value = 0.28). The relatively few vaccinated individuals limited the study’s power to assess the role of vaccination. Conclusions Stroke and MI rates are transiently increased after

  20. Synchronous inhibitory potentials precede seizure-like events in acute models of focal limbic seizures.

    PubMed

    Uva, Laura; Breschi, Gian Luca; Gnatkovsky, Vadym; Taverna, Stefano; de Curtis, Marco

    2015-02-18

    Interictal spikes in models of focal seizures and epilepsies are sustained by the synchronous activation of glutamatergic and GABAergic networks. The nature of population spikes associated with seizure initiation (pre-ictal spikes; PSs) is still undetermined. We analyzed the networks involved in the generation of both interictal and PSs in acute models of limbic cortex ictogenesis induced by pharmacological manipulations. Simultaneous extracellular and intracellular recordings from both principal cells and interneurons were performed in the medial entorhinal cortex of the in vitro isolated guinea pig brain during focal interictal and ictal discharges induced in the limbic network by intracortical and brief arterial infusions of either bicuculline methiodide (BMI) or 4-aminopyridine (4AP). Local application of BMI in the entorhinal cortex did not induce seizure-like events (SLEs), but did generate periodic interictal spikes sensitive to the glutamatergic non-NMDA receptor antagonist DNQX. Unlike local applications, arterial perfusion of either BMI or 4AP induced focal limbic SLEs. PSs just ahead of SLE were associated with hyperpolarizing potentials coupled with a complete blockade of firing in principal cells and burst discharges in putative interneurons. Interictal population spikes recorded from principal neurons between two SLEs correlated with a depolarizing potential. We demonstrate in two models of acute limbic SLE that PS events are different from interictal spikes and are sustained by synchronous activation of inhibitory networks. Our findings support a prominent role of synchronous network inhibition in the initiation of a focal seizure. Copyright © 2015 the authors 0270-6474/15/353048-08$15.00/0.

  1. Essential thrombocythemia in young individuals: frequency and risk factors for vascular events and evolution to myelofibrosis in 126 patients.

    PubMed

    Alvarez-Larrán, A; Cervantes, F; Bellosillo, B; Giralt, M; Juliá, A; Hernández-Boluda, J C; Bosch, A; Hernández-Nieto, L; Clapés, V; Burgaleta, C; Salvador, C; Arellano-Rodrigo, E; Colomer, D; Besses, C

    2007-06-01

    The frequency of vascular events and evolution to myelofibrosis (MF) in young individuals with essential thrombocythemia (ET) is not well known. The incidence and predisposing factors to such complications was studied in 126 subjects diagnosed with ET at a median age of 31 years (range: 5-40). Overall survival and probability of survival free of thrombosis, bleeding and MF were analyzed by the Kaplan-Meier method and the presence of the Janus Kinase 2 (JAK2) V617F mutation correlated with the appearance of such complications. The JAK2 mutation (present in 43% of patients) was associated with higher hemoglobin (Hb) (P<0.001) and lower platelets at diagnosis. With a median follow-up of 10 years (range: 4-25), 31 thrombotic events were registered (incidence rate: 2.2 thromboses/100 patients/year). When compared with the general population, young ET patients showed a significant increase in stroke (odds ratio 50, 95% CI: 21.5-115) and venous thromboses (odds ratio 5.3, 95% CI: 3.9-10.6). Thrombosis-free survival was 84% at 10 years, with tobacco use being associated with higher risk of thrombosis. Actuarial freedom from evolution to MF was 97% at 10 years. In conclusion, young ET patients have thrombotic events, especially stroke and venous thrombosis, more frequently than generally considered, whereas they rarely transform to MF.

  2. Relationship Between Acute Benzodiazepine Poisoning and Acute Pancreatitis Risk

    PubMed Central

    Liaw, Geng-Wang; Hung, Dong-Zong; Chen, Wei-Kung; Lin, Cheng-Li; Lin, I-Ching; Kao, Chia-Hung

    2015-01-01

    Abstract We designed a population-based retrospective cohort study to investigate the association between the event of benzodiazepine (BZD) poisoning and the risk of acute pancreatitis. In the present study, 12,893 patients with BZD poisoning during 2000 to 2011 were enrolled and matched with 4 comparison patients according to mean age and sex. We determined the cumulative incidences and adjusted hazard ratios of acute pancreatitis. A significant association was observed between BZD poisoning and acute pancreatitis. After adjustment for potential risk factors, the patients with BZD poisoning had a 5.33-fold increased risk of acute pancreatitis compared with the controls without BZD poisoning (HR = 5.33, 95% CI = 2.26–12.60). The results revealed that acute pancreatitis in patients with BZD poisoning occurred in a follow-up time of ≤1 month (HR = 50.0, P < .001), and the risk of acute pancreatitis was no different between the patients with and without BZD poisoning when the follow-up time was >1 month (HR = 1.07, P > .05). This population-based study revealed the positive correlation between the event of BZD poisoning and an increased risk of acute pancreatitis. The findings warrant further large-scale and in-depth investigation. PMID:26717383

  3. [Intraoperative monitoring of oxygen tissue pressure: Applications in vascular neurosurgery].

    PubMed

    Arikan, Fuat; Vilalta, Jordi; Torne, Ramon; Chocron, Ivette; Rodriguez-Tesouro, Ana; Sahuquillo, Juan

    2014-01-01

    Ischemic lesions related to surgical procedures are a major cause of postoperative morbidity in patients with cerebral vascular disease. There are different systems of neuromonitoring to detect intraoperative ischemic events, including intraoperative monitoring of oxygen tissue pressure (PtiO2). The aim of this article was to describe, through the discussion of 4 cases, the usefulness of intraoperative PtiO2 monitoring during vascular neurosurgery. In presenting these cases, we demonstrate that monitoring PtiO2 is a reliable way to detect early ischemic events during surgical procedures. Continuous monitoring of PtiO2 in an area at risk allows the surgeon to resolve the cause of the ischemic event before it evolves to an established cerebral infarction. Copyright © 2014 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  4. Contemporary management of acute coronary syndromes: does the practice match the evidence? The global registry of acute coronary events (GRACE).

    PubMed

    Carruthers, K F; Dabbous, O H; Flather, M D; Starkey, I; Jacob, A; Macleod, D; Fox, K A A

    2005-03-01

    To determine to what extent evidence based guidelines are followed in the management of acute coronary syndromes (ACS) in the UK, elsewhere in Europe, and multinationally, and what the outcomes are. Multinational, prospective, observational registry (GRACE, global registry of acute coronary events) with six months' follow up. Patients presenting to a cluster of hospitals. The study was designed to collect data representative of the full spectrum of ACS in specific geographic populations. Patients admitted with a working diagnosis of unstable angina or suspected myocardial infarction (MI). Death during hospitalisation and at six months' follow up (adjusted for baseline risks). In ST elevation MI, reperfusion was applied more often in the UK (71%) than in Europe (65%) and multinationally (59%) (p < 0.01). However, this was almost entirely by lytic treatment, in contrast with elsewhere (primary percutaneous coronary intervention 1%, 29%, 16%, respectively). Statins were applied more frequently in the UK for all classes of patients with ACS (p < 0.0001). In contrast there was lower use of revascularisation procedures in non-ST MI (20% v 37% v 28%, respectively) and glycoprotein IIb/IIIa antagonists (6% v 25% v 26%, respectively). In-hospital death rates, adjusted for baseline risk, were not significantly different but six month death rates were higher in the UK for ST elevation MI (7.2% UK, 4.3% Europe, 5.3% multinationally; p < 0.0001) and non-ST elevation MI (7.5%, 6.2%, and 6.7%, respectively; p = 0.012, UK v Europe). Current management of ACS in the UK more closely follows the recommendations of the National Service Framework than British or European guidelines. Differences in practice may account for the observed higher event rates in the UK after hospital discharge.

  5. [The balance of markers of regulation vascular tone and fibrinogen in the prognosis of hemorrhagic transformation and fatal outcome in the acute period of ischemic stroke].

    PubMed

    Liang, O V; Kochetov, A G; Arkhipkin, A A; Novozhenova, Iu V; Shamalov, N A; Ramazanov, G R; Chuĭko, M R; Ogurtsov, P P; Skvortsova, V I

    2012-01-01

    The markers of regulation vascular tone, such as rennin, endothelin-1, and C-type natriuretic peptide, are of great value for prognosis of hemorrhagic transformation and fatal outcome of ischemic stroke. A change in the vascular tone in case of hemorrhagic transformation at the affected site precedes activation of the coagulation component of hemostasis as a mechanism preventing blood loss and increasing fibrinogen level. This work was aimed to study the balance of the above markers and fibrinogen in the prognosis of hemorrhagic transformation and fatal outcome in the acute period of ischemic stroke. It included 62 patients receiving no thrombolytic therapy. It was shown that symptomatic hemorrhagic transformation was associated with elevated rennin levels without a marked fall in the level of C-type natriuretic peptide and asymptomatic hemorrhagic transformation with elevated endothelin-1 levels and decreased concentration of natriuretic peptide. Fibrinogen level on day 4 of the observation proved to be a reliable predictor of negative prognosis. Asymptomatic hemorrhagic transformation without fatal outcome was associated with systemic and local vasoconstriction and inhibition of local vasodilation. Symptomatic hemorrhagic transformation with the fatal outcome was accompanied by dysregulation of vascular tone in the form of activation of systemic and local vasoconstriction, insufficient inhibition of local vasodilation and compensatory reaction in the form of activation of hemostatic mechanisms manifest as elevated fibrinogen levels on day 4. The lethal outcome without hemorrhagic transformation was associated with systemic vasoconstriction, activation of local vasodilation and vasoconstriction leading to local "biochemical paralysis" of vascular tone regulation.

  6. Impact of aspirin on presentation and hospital outcomes in patients with acute coronary syndromes (The Global Registry of Acute Coronary Events [GRACE]).

    PubMed

    Spencer, Frederick A; Santopinto, Jose J; Gore, Joel M; Goldberg, Robert J; Fox, Keith A A; Moscucci, Mauro; White, Kami; Gurfinkel, Enrique P

    2002-11-15

    The long-term use of aspirin (ASA) reduces the risk of subsequent acute coronary syndromes in patients with coronary artery disease (CAD). It is less clear whether ASA therapy benefits patients who develop an acute coronary syndrome despite its use. Baseline characteristics, type of acute coronary syndrome, and in-hospital events were compared on the basis of previous use of ASA in 11,388 patients with and without a history of CAD presenting to 94 multinational hospitals. A total of 73.0% of patients with a history of CAD (n = 4,974) were previously on long-term ASA therapy compared with 19.4% of patients without a history of CAD (n = 6,414). After multivariate regression analysis controlling for various potentially confounding factors, patients with a history of CAD who were previously taking ASA were significantly less likely to present with ST-segment elevation myocardial infarction (MI) (adjusted odds ratio [OR] 0.52, 95% confidence intervals [CI] 0.44 to 0.61) or die during hospitalization (OR 0.69, 95% CI 0.50 to 0.95) in comparison to patients who were not taking ASA. Patients without a history of CAD and who were previously taking ASA also had a lower risk of developing ST-segment elevation MI (OR 0.35, 95% CI 0.30 to 0.40) and a trend toward a decreased hospital death rate (OR 0.77, 95% CI 0.55 to 1.07). These results demonstrate that patients with a history of CAD who present with an acute coronary syndrome despite prior ASA use have less severe clinical presentation, fewer hospital complications, and lower in-hospital death rates than patients not previously taking ASA.

  7. Socio-Economic and Clinical Factors as Predictors of Disease Evolution and Acute Events in COPD Patients

    PubMed Central

    Pandolfi, Paolo; Zanasi, Alessandro; Musti, Muriel Assunta; Stivanello, Elisa; Pisani, Lara; Angelini, Sabrina; Maffei, Francesca; Hrelia, Silvana; Angeloni, Cristina; Zenesini, Corrado; Hrelia, Patrizia

    2015-01-01

    Background Socio-economic, cultural and environmental factors are becoming increasingly important determinants of chronic obstructive pulmonary disease (COPD). We conducted a study to investigate socio-demographic, lifestyle and clinical factors, and to assess their role as predictors of acute events (mortality or hospitalization for respiratory causes) in a group of COPD patients. Methods Subjects were recruited among outpatients who were undertaking respiratory function tests at the Pneumology Unit of the Sant’Orsola-Malpighi Hospital, Bologna. Patients were classified according to the GOLD Guidelines. Results 229 patients with COPD were included in the study, 44 with Mild, 68 Moderate, 52 Severe and 65 Very Severe COPD (GOLD stage). Significant differences among COPD stage, in terms of smoking status and fragility index, were detected. COPD stage significantly affected the values of all clinical tests (spirometry and ABG analysis). Kaplan-Meier estimates showed a significant difference between survival curves by COPD stage with lower event-free probability in very severe COPD stage. Significant risk factors for acute events were: underweight (HR = 4.08; 95% CI 1.01–16.54), having two or more comorbidities (HR = 4.71; 95% CI 2.52–8.83), belonging to moderate (HR = 3.50; 95% CI 1.01–12.18) or very severe COPD stage (HR = 8.23; 95% CI 2.35–28.85). Conclusions Our findings indicate that fragility is associated with COPD stage and that comorbidities and the low body mass index are predictors of mortality or hospitalization. Besides spirometric analyses, FeNO measure and comorbidities, body mass index could also be considered in the management and monitoring of COPD patients. PMID:26252571

  8. The Renin-Angiotensin-Aldosterone System in Vascular Inflammation and Remodeling

    PubMed Central

    Pacurari, Maricica; Kafoury, Ramzi; Tchounwou, Paul B.; Ndebele, Kenneth

    2014-01-01

    The RAAS through its physiological effectors plays a key role in promoting and maintaining inflammation. Inflammation is an important mechanism in the development and progression of CVD such as hypertension and atherosclerosis. In addition to its main role in regulating blood pressure and its role in hypertension, RAAS has proinflammatory and profibrotic effects at cellular and molecular levels. Blocking RAAS provides beneficial effects for the treatment of cardiovascular and renal diseases. Evidence shows that inhibition of RAAS positively influences vascular remodeling thus improving CVD outcomes. The beneficial vascular effects of RAAS inhibition are likely due to decreasing vascular inflammation, oxidative stress, endothelial dysfunction, and positive effects on regeneration of endothelial progenitor cells. Inflammatory factors such as ICAM-1, VCAM-1, TNFα, IL-6, and CRP have key roles in mediating vascular inflammation and blocking RAAS negatively modulates the levels of these inflammatory molecules. Some of these inflammatory markers are clinically associated with CVD events. More studies are required to establish long-term effects of RAAS inhibition on vascular inflammation, vascular cells regeneration, and CVD clinical outcomes. This review presents important information on RAAS's role on vascular inflammation, vascular cells responses to RAAS, and inhibition of RAAS signaling in the context of vascular inflammation, vascular remodeling, and vascular inflammation-associated CVD. Nevertheless, the review also equates the need to rethink and rediscover new RAAS inhibitors. PMID:24804145

  9. Dermatopathology effects of simulated solar particle event radiation exposure in the porcine model.

    PubMed

    Sanzari, Jenine K; Diffenderfer, Eric S; Hagan, Sarah; Billings, Paul C; Gridley, Daila S; Seykora, John T; Kennedy, Ann R; Cengel, Keith A

    2015-07-01

    The space environment exposes astronauts to risks of acute and chronic exposure to ionizing radiation. Of particular concern is possible exposure to ionizing radiation from a solar particle event (SPE). During an SPE, magnetic disturbances in specific regions of the Sun result in the release of intense bursts of ionizing radiation, primarily consisting of protons that have a highly variable energy spectrum. Thus, SPE events can lead to significant total body radiation exposures to astronauts in space vehicles and especially while performing extravehicular activities. Simulated energy profiles suggest that SPE radiation exposures are likely to be highest in the skin. In the current report, we have used our established miniature pig model system to evaluate the skin toxicity of simulated SPE radiation exposures that closely resemble the energy and fluence profile of the September, 1989 SPE using either conventional radiation (electrons) or proton simulated SPE radiation. Exposure of animals to electron or proton radiation led to dose-dependent increases in epidermal pigmentation, the presence of necrotic keratinocytes at the dermal-epidermal boundary and pigment incontinence, manifested by the presence of melanophages in the derm is upon histological examination. We also observed epidermal hyperplasia and a reduction in vascular density at 30 days following exposure to electron or proton simulated SPE radiation. These results suggest that the doses of electron or proton simulated SPE radiation results in significant skin toxicity that is quantitatively and qualitatively similar. Radiation-induced skin damage is often one of the first clinical signs of both acute and non-acute radiation injury where infection may occur, if not treated. In this report, histopathology analyses of acute radiation-induced skin injury are discussed. Copyright © 2015 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

  10. Management and outcomes following an acute coronary event in patients with chronic heart failure 1999-2007.

    PubMed

    Ranasinghe, Isuru; Naoum, Chris; Aliprandi-Costa, Bernadette; Sindone, Andrew P; Steg, P Gabriel; Elliott, John; McGarity, Bruce; Lefkovits, Jeffrey; Brieger, David

    2012-05-01

    The outcome of patients with chronic heart failure (CHF) following an ischaemic event is poorly understood. We evaluated the management and outcomes of CHF patients presenting with an acute coronary syndrome (ACS) and explored changes in outcomes over time. A total of 5556 patients enrolled in the Australia-New Zealand population of the Global Registry of Acute Coronary Events (GRACE) between 1999 and 2007 were included. Patients with CHF (n = 609) were compared with those without CHF (n = 4947). Patients with CHF were on average 10 years older, were more likely to be female, had more co-morbidities and cardiac risk factors, and were more likely to have a prior history of angina, myocardial infarction, and revascularization by coronary artery bypass graft (CABG) when compared with those without CHF. CHF was associated with a substantial increase in in-hospital renal failure [odds ratio (OR) 1.76, 95% confidence interval (CI) 1.15-2.71], readmission post-discharge (OR 1.47, 95% CI 1.17-1.90), and 6-month mortality (OR 2.25, 95% CI 1.55-3.27). Over the 9 year study period, in-hospital and 6 month mortality in those with CHF declined by absolute rates of 7.5% and 14%, respectively. This was temporally associated with an increase in prescription of thienopyridines, beta-blockers, statins, and angiotensin II receptor blockers, increased rates of coronary angiography, and 31.8% absolute increase in referral rates for cardiac rehabilitation. Acute coronary syndrome patients with pre-existing CHF are a very high risk group and carry a disproportionate mortality burden. Encouragingly, there was a marked temporal improvement in outcomes over a 9 year period with an increase in evidence-based treatments and secondary preventative measures.

  11. Transient ischemic attack and minor stroke are the most common manifestations of acute cerebrovascular disease: a prospective, population-based study--the Aarhus TIA study.

    PubMed

    von Weitzel-Mudersbach, Paul; Andersen, Grethe; Hundborg, Heidi H; Johnsen, Søren P

    2013-01-01

    Severity of acute vascular illness may have changed in the last decades due to improvements in primary and secondary prevention. Population-based data on the severity of acute ischemic cerebrovascular disease are sparse. We aimed to examine incidence, characteristics and severity of acute ischemic cerebrovascular disease in a well-defined population. All patients admitted with transient ischemic attack (TIA) or acute ischemic stroke from March 1, 2007, to February 29, 2008, with residence in the Aarhus area, were included. Incidence rates and characteristics of TIA and ischemic stroke were compared. TIA accounted for 30%, TIA and minor stroke combined for 65% of all acute ischemic cerebrovascular events. Age-adjusted incidence rates of TIA and ischemic stroke were 72.2/100,000 and 129.5/100,000 person-years, respectively. TIA patients were younger than stroke patients (66.3 vs. 72.7 years; p < 0.001). Atrial fibrillation, previous myocardial infarction and previous stroke were significantly more frequent in stroke patients; no differences in other baseline characteristics were found. Minor events are the most common in ischemic cerebrovascular disease, and may constitute a larger proportion than previously reported. TIA and stroke patients share many characteristics; however, TIA patients are younger and have fewer manifestations of atherosclerotic diseases, indicating a high potential for secondary prevention. Copyright © 2012 S. Karger AG, Basel.

  12. Phytochemical genistein in the regulation of vascular function: new insights.

    PubMed

    Si, Hongwei; Liu, Dongmin

    2007-01-01

    Genistein, a natural bioactive compound derived from legumes, has drawn wide attention during the last decade because of its potentially beneficial effects on some human degenerative diseases. It has a weak estrogenic effect and is a well-known non-specific tyrosine kinase inhibitor at pharmacological doses. Epidemiological studies show that genistein intake is inversely associated with the risk of cardiovascular diseases. Data from animal and in vitro studies suggest a protective role of genistein in cardiovascular events. However, the mechanisms of the genistein action on vascular protective effects are unclear. Past extensive studies exploring its hypolipidemic effect resulted in contradictory data. Genistein also is a relatively poor antioxidant. However, genistein protects against pro-inflammatory factor-induced vascular endothelial barrier dysfunction and inhibits leukocyte-endothelium interaction, thereby modulating vascular inflammation, a major event in the pathogenesis of atherosclerosis. Recent studies found that genistein exerts a novel non-genomic action by targeting on important signaling molecules in vascular endothelial cells (ECs). Genistein rapidly activates endothelial nitric oxide synthase and production of nitric oxide in ECs. This genistein effect is novel since it is independent of its known effects, but mediated by the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) cascade. Further studies demonstrated that genistein directly stimulates the plasma membrane-associated adenylate cyclases, leading to activation of the cAMP signaling pathway. In addition, genistein activates peroxisome proliferator-activated receptors, ligand-activated nuclear receptors important to normal vascular function. Furthermore, genistein reduces reactive oxygen species (ROS) by attenuating the expression of ROS-producing enzymes. These new findings reveal the novel roles for genistein in the regulation of vascular function and provide a basis for further

  13. [A cohort study on the predictive value of factors influencing cardio-cerebro vascular death among people over 40 years of age].

    PubMed

    Yang, Jian-min; Lu, Fang-hong; Jin, Shi-kuan; Sun, Shang-wen; Zhao, Ying-xin; Wang, Shu-jian; Zhou, Xiao-hong

    2007-02-01

    To explore the factors influencing cardio-cerebro vascular death events among people over 40 years of age in Shandong area, China. Baseline survey was carried out in 1991. A total number of 11,008 adults over 40 years old had been studied in Shandong province. Data on cardiocerebro death was collected. The correlation between influencing factors and cardio-cerebro vascular death events was analyzed by Cox regression model. Totally, 434 cardio-cerebro death events occurred among the 11,008 subjects during the 8-year follow-up study. Cardio-cerebro death events were related to systolic blood pressure, diastolic blood pressure, smoking, stroke history and age. Data from Cox regression analysis showed that the relative risk (RR) for cardio-cerebro vascular death events increased by 2.862 [95% confidence interval (CI): 1.976-4.144] times for those people having stroke history. When systolic blood pressure, diastolic blood pressure increased by every 10 mm Hg, the relative risk for cardio-cerebro vascular death events increased by 1.171 (95% CI: 1.033-1.328), 1.214 (95% CI: 1.044-1.413) respectively. it was found that a 1.239 (95% CI: 1.088-1.553) times higher in smokers than non-smokers on relative risk for cardio-cerebro vascular death events. However, the predictive values of the influencing factors for cardio-cerebro vascular death were different among population of different years of age. The relative risk for cardio-cerebro vascular death events increased by 1.366 (95% CI: 1.102-1.678) times for each 10 mm Hg increase of diastolic blood pressure in 40-59 years old population. However, the effect was taken place by systolic blood pressure in 60-74 years old population,with a relative risk of 1.201 (95% CI: 1.017-1.418) for each 10 mm Hg increase. Age seemed the only significant factor for cardio-cerebro vascular death events on population aged more than 75 years old. Conclusion The predictive values of the risk factors were different among age groups. The different

  14. Vascular disease, ESRD, and death: interpreting competing risk analyses.

    PubMed

    Grams, Morgan E; Coresh, Josef; Segev, Dorry L; Kucirka, Lauren M; Tighiouart, Hocine; Sarnak, Mark J

    2012-10-01

    Vascular disease, a common condition in CKD, is a risk factor for mortality and ESRD. Optimal patient care requires accurate estimation and ordering of these competing risks. This is a prospective cohort study of screened (n=885) and randomized participants (n=837) in the Modification of Diet in Renal Disease study (original study enrollment, 1989-1992), evaluating the association of vascular disease with ESRD and pre-ESRD mortality using standard survival analysis and competing risk regression. The method of analysis resulted in markedly different estimates. Cumulative incidence by standard analysis (censoring at the competing event) implied that, with vascular disease, the 15-year incidence was 66% and 51% for ESRD and pre-ESRD death, respectively. A more accurate representation of absolute risk was estimated with competing risk regression: 15-year incidence was 54% and 29% for ESRD and pre-ESRD death, respectively. For the association of vascular disease with pre-ESRD death, estimates of relative risk by the two methods were similar (standard survival analysis adjusted hazard ratio, 1.63; 95% confidence interval, 1.20-2.20; competing risk regression adjusted subhazard ratio, 1.57; 95% confidence interval, 1.15-2.14). In contrast, the hazard and subhazard ratios differed substantially for other associations, such as GFR and pre-ESRD mortality. When competing events exist, absolute risk is better estimated using competing risk regression, but etiologic associations by this method must be carefully interpreted. The presence of vascular disease in CKD decreases the likelihood of survival to ESRD, independent of age and other risk factors.

  15. Natural antioxidant ice cream acutely reduces oxidative stress and improves vascular function and physical performance in healthy individuals.

    PubMed

    Sanguigni, Valerio; Manco, Melania; Sorge, Roberto; Gnessi, Lucio; Francomano, Davide

    2017-01-01

    The formation of reactive oxygen species (ROS) contributes to the pathogenesis and progression of several diseases. Polyphenols have been shown to be beneficial against ROS. The aim of this study was to evaluate the effects of a natural antioxidant ice cream on oxidative stress, vascular function, and physical performance. In this controlled, single-blind, crossover study, 14 healthy individuals were randomized to consume 100 g of either antioxidant ice cream containing dark cocoa powder and hazelnut and green tea extracts or milk chocolate ice cream (control ice cream). Participants were studied at baseline and 2 h after ingesting ice cream. Serum polyphenols, antioxidant status (ferric-reducing ability of plasma [FRAP]), nitric oxide (NOx) bioavailability, markers of oxidative stress (determination of reactive oxygen metabolites [d-ROMs] and hydrogen peroxide [H 2 O 2 ]), endothelium function (flow-mediated dilation [FMD] and reactive hyperemia index [RHI]), and exercise tolerance (stress test) were assessed, and the double product was measured. Serum polyphenols (P < 0.001), NOx (P < 0.001), FRAP (P < 0.005), FMD (P < 0.001), and RHI (P < 0.05) increased significantly, oxidative stress decreased (d-Roms, P < 0.001; H 2 O 2 , P < 0.001), and the double product (P < 0.001) was improved only after antioxidant ice cream ingestion. No changes were found after control ice cream ingestion. To our knowledge, this is the first study to demonstrate that a natural ice cream rich in polyphenols acutely improved vascular function and physical performance in healthy individuals through a reduction in oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. ACTINOMYCES NEUII ENDOPHTHALMITIS AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTION.

    PubMed

    Sahni, Sakshi; Watson, Randee Miller; Sheth, Veeral S

    2017-01-01

    To describe a case of acute endophthalmitis caused by Actinomyces neuii after intravitreal anti-vascular endothelial growth factor injection. Observational case report, review of published literature. A 67-year-old white man with wet age-related macular degeneration developed endophthalmitis secondary to A. neuii on the 10th day after intravitreal anti-vascular endothelial growth factor injection. Both anterior chamber and vitreous cultures were positive for A. neuii. He was treated successfully with intravitreal injection of vancomycin and ceftazidime. This is the first published report of culture-positive endophthalmitis caused by A. neuii after intravitreal injection.

  17. Investigation of the vascular reaction of the nasal mucosa in cosmonauts

    NASA Technical Reports Server (NTRS)

    Yakovleva, I. Y.; Baranova, V. P.

    1982-01-01

    Rhinopneumometric examinations in 3 positions of the body were undertaken in 36 cosmonauts aged 25 to 45 years, 14 of whom participated in space flights of various lengths. The nasal vascular response standards were defined in persons of the group examined. A subjective characteristic of the nasal vascular, reactions arising during the flight is provided. Examinations of 14 people were performed before and after the space flight. The rise of intranasal resistance in the horizontal body position permits forecasting different degrees of nasal breathing disturbances during a period of acute adaptation to weightlessness owing to vasomotor alterations of the nasal mucous membrane.

  18. Adverse cardiovascular events in acute coronary syndrome with indications for anticoagulation.

    PubMed

    Knight, Stacey; McCubrey, Raymond O; Yuan, Zhong; Woller, Scott C; Horne, Benjamin D; Bunch, T Jared; Le, Viet T; Mills, Roger M; Muhlestein, Joseph B

    2016-08-01

    Randomized acute coronary syndrome (ACS) trials testing various antithrombotic (AT) regimens have largely excluded patients with coexisting conditions and indications for anticoagulation (AC). The purpose of this study is to examine the 2-year clinical outcomes of patients with ACS with indication for AC due to venous thromboembolism (VTE) during hospitalization for the ACS event or a prior or new diagnosis of atrial fibrillation (AF) with a CHADS2 (Congestive heart failure; Hypertension; Age; Diabetes; previous ischemic Stroke) score ⩾2. ACS patients with AC indication from 2004 to 2009 were identified (n = 619). A Cox proportional hazards model was used to examine the primary efficacy outcome of major adverse cardiovascular events (MACE) including all-cause death, myocardial infarction (MI) or stroke. The primary explanatory variable was at-discharge antithrombotic strategy [single antiplatelet ± AC, dual antiplatelet (DAP) ± AC or AC only; referent DAP + AC]. A total of 261 (42.2%) patients had a MACE event. AT strategy was not a significant factor for MACE (all p > 0.09). The factors associated with MACE were high mortality risk score [hazard ratio (HR)=1.87, 95% confidence interval (CI): 1.39- 2.52; p < 0.001), prior MI (HR = 1.44, 95% CI: 1.03-2.01; p= 0.033) and presentation of ST elevation MI (HR = 2.70, 95% CI: 1.61-4.51; p < 0.001) or non-ST elevation MI (HR = 1.70, 95% CI: 1.15-2.49; p < 0.001) compared with angina. In this real world observational study, the at-discharge AT strategy was not significantly associated with the 2-year risk of MACE. These findings do not negate the need for randomized trials to generate evidence-based approaches to management of this important population. © The Author(s), 2016.

  19. Adverse cardiovascular events in acute coronary syndrome with indications for anticoagulation

    PubMed Central

    Knight, Stacey; McCubrey, Raymond O.; Yuan, Zhong; Woller, Scott C.; Horne, Benjamin D.; Bunch, T. Jared; Le, Viet T.; Mills, Roger M.; Muhlestein, Joseph B.

    2016-01-01

    Objectives: Randomized acute coronary syndrome (ACS) trials testing various antithrombotic (AT) regimens have largely excluded patients with coexisting conditions and indications for anticoagulation (AC). The purpose of this study is to examine the 2-year clinical outcomes of patients with ACS with indication for AC due to venous thromboembolism (VTE) during hospitalization for the ACS event or a prior or new diagnosis of atrial fibrillation (AF) with a CHADS2 (Congestive heart failure; Hypertension; Age; Diabetes; previous ischemic Stroke) score ⩾2. Methods: ACS patients with AC indication from 2004 to 2009 were identified (n = 619). A Cox proportional hazards model was used to examine the primary efficacy outcome of major adverse cardiovascular events (MACE) including all-cause death, myocardial infarction (MI) or stroke. The primary explanatory variable was at-discharge antithrombotic strategy [single antiplatelet ± AC, dual antiplatelet (DAP) ± AC or AC only; referent DAP + AC]. Results: A total of 261 (42.2%) patients had a MACE event. AT strategy was not a significant factor for MACE (all p > 0.09). The factors associated with MACE were high mortality risk score [hazard ratio (HR)=1.87, 95% confidence interval (CI): 1.39– 2.52; p < 0.001), prior MI (HR = 1.44, 95% CI: 1.03–2.01; p= 0.033) and presentation of ST elevation MI (HR = 2.70, 95% CI: 1.61–4.51; p < 0.001) or non-ST elevation MI (HR = 1.70, 95% CI: 1.15–2.49; p < 0.001) compared with angina. Conclusions: In this real world observational study, the at-discharge AT strategy was not significantly associated with the 2-year risk of MACE. These findings do not negate the need for randomized trials to generate evidence-based approaches to management of this important population. PMID:26920371

  20. El Salvador earthquakes: relationships among acute stress disorder symptoms, depression, traumatic event exposure, and resource loss.

    PubMed

    Sattler, David N; de Alvarado, Ana Maria Glower; de Castro, Norma Blandon; Male, Robert Van; Zetino, A M; Vega, Raphael

    2006-12-01

    Four and seven weeks after powerful earthquakes in El Salvador, the authors examined the relationships among demographics, traumatic event exposure, social support, resource loss, acute stress disorder (ASD) symptoms, depression, and posttraumatic growth. Participants were 253 college students (Study 1) and 83 people in the community (Study 2). In Study 1, female gender, traumatic event exposure, low social support, and loss of personal characteristic, condition, and energy resources contributed to ASD symptoms and depression. In Study 2, damage to home and loss of personal characteristic and object resources contributed to ASD symptoms and depression. Posttraumatic growth was not associated with ASD symptoms or depression. Findings support the conservation of resources stress theory (Hobfoll, 1998). Resource loss spirals, excessive demands on coping, and exposure to multiple disasters are discussed.

  1. [An health education program for patients admitted to CCU for an acute coronary event].

    PubMed

    Amodeo, Raffaello; De Ponti, Anna; Sorbara, Loredana; Imperatore, Patrizia Fusar; Berizzi, Margherita; Di Rocco, Egidia; Saltarel, Ivan; Marigliani, Catia; Avanzini, Fausto

    2006-01-01

    In spite of the broad recognition of the importance of health education, time for structured one-to -one initiatives of health education during the hospital stay is limited. The organization of an health education meeting for patients admitted to CCU for an acute coronary event is described. The planning and implementation of the initiative lasted two years and involved 7 nurses and one doctor. The organization required efforts related to the event itself (preparation of training aids, identification or contents and methods for delivery) but also organizative changes. Dietitians in fact had to be involved because the healthy diet recommended was different from the hospital diet. The assessment of the effectiveness of the health education was also planned: administration of a questionnaire to explore lifestyles and knowledge of the illness before and after the meeting; phone interviews after 3, 6 and 12 months from the meeting. Since may 2003, in the first 3 years 74 meetings have been organised, involving 507 patients and 329 relatives. Each meeting lasts 2 hours and contents delivered encompass the coronary event, risk factors and their modification, healthy lifestyles. Initial preliminary results on the impact of the meeting on lifestyle changes are promising. Initiatives are ongoing to include this activity among officially recognised nursing activities.

  2. Vascular Cells in Blood Vessel Wall Development and Disease.

    PubMed

    Mazurek, R; Dave, J M; Chandran, R R; Misra, A; Sheikh, A Q; Greif, D M

    2017-01-01

    The vessel wall is composed of distinct cellular layers, yet communication among individual cells within and between layers results in a dynamic and versatile structure. The morphogenesis of the normal vascular wall involves a highly regulated process of cell proliferation, migration, and differentiation. The use of modern developmental biological and genetic approaches has markedly enriched our understanding of the molecular and cellular mechanisms underlying these developmental events. Additionally, the application of similar approaches to study diverse vascular diseases has resulted in paradigm-shifting insights into pathogenesis. Further investigations into the biology of vascular cells in development and disease promise to have major ramifications on therapeutic strategies to combat pathologies of the vasculature. © 2017 Elsevier Inc. All rights reserved.

  3. Bioprinting for vascular and vascularized tissue biofabrication.

    PubMed

    Datta, Pallab; Ayan, Bugra; Ozbolat, Ibrahim T

    2017-03-15

    Bioprinting is a promising technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision. Bioprinting enables the deposition of various biologics including growth factors, cells, genes, neo-tissues and extra-cellular matrix-like hydrogels. Benefits of bioprinting have started to make a mark in the fields of tissue engineering, regenerative medicine and pharmaceutics. Specifically, in the field of tissue engineering, the creation of vascularized tissue constructs has remained a principal challenge till date. However, given the myriad advantages over other biofabrication methods, it becomes organic to expect that bioprinting can provide a viable solution for the vascularization problem, and facilitate the clinical translation of tissue engineered constructs. This article provides a comprehensive account of bioprinting of vascular and vascularized tissue constructs. The review is structured as introducing the scope of bioprinting in tissue engineering applications, key vascular anatomical features and then a thorough coverage of 3D bioprinting using extrusion-, droplet- and laser-based bioprinting for fabrication of vascular tissue constructs. The review then provides the reader with the use of bioprinting for obtaining thick vascularized tissues using sacrificial bioink materials. Current challenges are discussed, a comparative evaluation of different bioprinting modalities is presented and future prospects are provided to the reader. Biofabrication of living tissues and organs at the clinically-relevant volumes vitally depends on the integration of vascular network. Despite the great progress in traditional biofabrication approaches, building perfusable hierarchical vascular network is a major challenge. Bioprinting is an emerging technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision

  4. The course of posttraumatic stress symptoms and functional impairment following a disaster: what is the lasting influence of acute vs. ongoing traumatic events and stressors?

    PubMed Central

    Cerdá, M.; Bordelois, P.M.; Galea, S.; Norris, F.; Tracy, M.; Koenen, K.C.

    2012-01-01

    Purpose Ongoing traumatic events and stressors, rather than acute sources of trauma, may shape long-term post-disaster mental health. The purpose of this study was to compare the influence of acute hurricane-related exposures and ongoing post-hurricane exposures on the short- and long-term course of posttraumatic stress symptoms (PTSS) and functional impairment (FI). Methods A random sample of adults (n=658) in Galveston and Chambers Counties, Texas, was selected 2–6 months after Hurricane Ike and interviewed 3 times over eighteen months. Hurricane-related exposures included traumatic events such as death of a family member due to the hurricane and stressors such as loss/damage to personal property due to the hurricane. Post-hurricane exposures included traumatic events such as sexual assault and stressors such as divorce or serious financial problems. Results Experiencing an acute hurricane-related traumatic event or stressor was associated with initial post-hurricane PTSS [RR=1.92(95% CI=1.13–3.26) and RR=1.62(1.36–1.94), respectively] and FI [RR=1.76; (1.05–2.97) and RR=1.74(1.46–2.08)], respectively, and acute hurricane-related stressors were associated with a higher rate of increase in FI over time [RR=1.09; (1.01–1.19)]. In contrast, ongoing post-hurricane daily stressors were not associated within initial PTSS and FI, but were associated with PTSS and FI at the second and third interviews. Conclusions While immediate postdisaster interventions may influence short-term mental health, investment in the prevention of ongoing stressors may be instrumental to manage long-term mental health status. PMID:22878832

  5. Optimal combination treatment and vascular outcomes in recent ischemic stroke patients by premorbid risk level.

    PubMed

    Park, Jong-Ho; Ovbiagele, Bruce

    2015-08-15

    Optimal combination of secondary stroke prevention treatment including antihypertensives, antithrombotic agents, and lipid modifiers is associated with reduced recurrent vascular risk including stroke. It is unclear whether optimal combination treatment has a differential impact on stroke patients based on level of vascular risk. We analyzed a clinical trial dataset comprising 3680 recent non-cardioembolic stroke patients aged ≥35 years and followed for 2 years. Patients were categorized by appropriateness levels 0 to III depending on the number of the drugs prescribed divided by the number of drugs potentially indicated for each patient (0=none of the indicated medications prescribed and III=all indicated medications prescribed [optimal combination treatment]). High-risk was defined as having a history of stroke or coronary heart disease (CHD) prior to the index stroke event. Independent associations of medication appropriateness level with a major vascular event (stroke, CHD, or vascular death), ischemic stroke, and all-cause death were analyzed. Compared with level 0, for major vascular events, the HR of level III in the low-risk group was 0.51 (95% CI: 0.20-1.28) and 0.32 (0.14-0.70) in the high-risk group; for stroke, the HR of level III in the low-risk group was 0.54 (0.16-1.77) and 0.25 (0.08-0.85) in the high-risk group; and for all-cause death, the HR of level III in the low-risk group was 0.66 (0.09-5.00) and 0.22 (0.06-0.78) in the high-risk group. Optimal combination treatment is related to a significantly lower risk of future vascular events and death among high-risk patients after a recent non-cardioembolic stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Do androgens play a beneficial role in the regulation of vascular tone? Nongenomic vascular effects of testosterone metabolites

    PubMed Central

    Perusquía, Mercedes

    2010-01-01

    The marked sexual dimorphism that exists in human cardiovascular diseases has led to the dogmatic concept that testosterone (Tes) has deleterious effects and exacerbates the development of cardiovascular disease in males. While some animal studies suggest that Tes does exert deleterious effects by enhancing vascular tone through acute or chronic mechanisms, accumulating evidence suggests that Tes and other androgens exert beneficial effects by inducing rapid vasorelaxation of vascular smooth muscle through nongenomic mechanisms. While this effect frequently has been observed in large arteries at micromolar concentrations, more recent studies have reported vasorelaxation of smaller resistance arteries at nanomolar (physiological) concentrations. The key mechanism underlying Tes-induced vasorelaxation appears to be the modulation of vascular smooth muscle ion channel function, particularly the inactivation of L-type voltage-operated Ca2+ channels and/or the activation of voltage-operated and Ca2+-activated K+ channels. Studies employing Tes analogs and metabolites reveal that androgen-induced vasodilation is a structurally specific nongenomic effect that is fundamentally different than the genomic effects on reproductive targets. For example, 5α-dihydrotestosterone exhibits potent genomic-androgenic effects but only moderate vasorelaxing activity, whereas its isomer 5β-dihydrotestosterone is devoid of androgenic effects but is a highly efficacious vasodilator. These findings suggest that the dihydro-metabolites of Tes or other androgen analogs devoid of androgenic or estrogenic effects could have useful therapeutic roles in hypertension, erectile dysfunction, prostatic ischemia, or other vascular dysfunctions. PMID:20228257

  7. Emotional stressors trigger cardiovascular events.

    PubMed

    Schwartz, B G; French, W J; Mayeda, G S; Burstein, S; Economides, C; Bhandari, A K; Cannom, D S; Kloner, R A

    2012-07-01

    To describe the relation between emotional stress and cardiovascular events, and review the literature on the cardiovascular effects of emotional stress, in order to describe the relation, the underlying pathophysiology, and potential therapeutic implications. Targeted PUBMED searches were conducted to supplement the authors' existing database on this topic. Cardiovascular events are a major cause of morbidity and mortality in the developed world. Cardiovascular events can be triggered by acute mental stress caused by events such as an earthquake, a televised high-drama soccer game, job strain or the death of a loved one. Acute mental stress increases sympathetic output, impairs endothelial function and creates a hypercoagulable state. These changes have the potential to rupture vulnerable plaque and precipitate intraluminal thrombosis, resulting in myocardial infarction or sudden death. Therapies targeting this pathway can potentially prevent acute mental stressors from initiating plaque rupture. Limited evidence suggests that appropriately timed administration of beta-blockers, statins and aspirin might reduce the incidence of triggered myocardial infarctions. Stress management and transcendental meditation warrant further study. © 2012 Blackwell Publishing Ltd.

  8. Reduction in Total Cardiovascular Events With Ezetimibe/Simvastatin Post-Acute Coronary Syndrome: The IMPROVE-IT Trial.

    PubMed

    Murphy, Sabina A; Cannon, Christopher P; Blazing, Michael A; Giugliano, Robert P; White, Jennifer A; Lokhnygina, Yuliya; Reist, Craig; Im, KyungAh; Bohula, Erin A; Isaza, Daniel; Lopez-Sendon, Jose; Dellborg, Mikael; Kher, Uma; Tershakovec, Andrew M; Braunwald, Eugene

    2016-02-02

    Intensive low-density lipoprotein cholesterol therapy with ezetimibe/simvastatin in IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) significantly reduced the first primary endpoint (PEP) in patients post-acute coronary syndrome (ACS) compared to placebo/simvastatin. This analysis tested the hypothesis that total events, including those beyond the first event, would also be reduced with ezetimibe/simvastatin therapy. All PEP events (cardiovascular [CV] death, myocardial infarction [MI], stroke, unstable angina [UA] leading to hospitalization, coronary revascularization ≥30 days post-randomization) during a median 6-year follow-up were analyzed in patients randomized to receive ezetimibe/simvastatin or placebo/simvastatin in IMPROVE-IT. Negative binomial regression was used for the primary analysis. Among 18,144 patients, there were 9,545 total PEP events (56% were first events and 44% subsequent events). Total PEP events were significantly reduced by 9% with ezetimibe/simvastatin vs placebo/simvastatin (incidence-rate ratio [RR]: 0.91; 95% confidence interval [CI]: 0.85 to 0.97; p = 0.007), as were the 3 pre-specified secondary composite endpoints and the exploratory composite endpoint of CV death, MI, or stroke (RR: 0.88; 95% CI: 0.81 to 0.96; p = 0.002). The reduction in total events was driven by decreases in total nonfatal MI (RR: 0.87; 95% CI: 0.79 to 0.96; p = 0.004) and total NF stroke (RR: 0.77; 95% CI: 0.65 to 0.93; p = 0.005). Lipid-lowering therapy with ezetimibe plus simvastatin improved clinical outcomes. Reductions in total PEP events, driven by reductions in MI and stroke, more than doubled the number of events prevented compared with examining only the first event. These data support continuation of intensive combination lipid-lowering therapy after an initial CV event. (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878). Copyright © 2016 American College of

  9. Vascular Disease, ESRD, and Death: Interpreting Competing Risk Analyses

    PubMed Central

    Coresh, Josef; Segev, Dorry L.; Kucirka, Lauren M.; Tighiouart, Hocine; Sarnak, Mark J.

    2012-01-01

    Summary Background and objectives Vascular disease, a common condition in CKD, is a risk factor for mortality and ESRD. Optimal patient care requires accurate estimation and ordering of these competing risks. Design, setting, participants, & measurements This is a prospective cohort study of screened (n=885) and randomized participants (n=837) in the Modification of Diet in Renal Disease study (original study enrollment, 1989–1992), evaluating the association of vascular disease with ESRD and pre-ESRD mortality using standard survival analysis and competing risk regression. Results The method of analysis resulted in markedly different estimates. Cumulative incidence by standard analysis (censoring at the competing event) implied that, with vascular disease, the 15-year incidence was 66% and 51% for ESRD and pre-ESRD death, respectively. A more accurate representation of absolute risk was estimated with competing risk regression: 15-year incidence was 54% and 29% for ESRD and pre-ESRD death, respectively. For the association of vascular disease with pre-ESRD death, estimates of relative risk by the two methods were similar (standard survival analysis adjusted hazard ratio, 1.63; 95% confidence interval, 1.20–2.20; competing risk regression adjusted subhazard ratio, 1.57; 95% confidence interval, 1.15–2.14). In contrast, the hazard and subhazard ratios differed substantially for other associations, such as GFR and pre-ESRD mortality. Conclusions When competing events exist, absolute risk is better estimated using competing risk regression, but etiologic associations by this method must be carefully interpreted. The presence of vascular disease in CKD decreases the likelihood of survival to ESRD, independent of age and other risk factors. PMID:22859747

  10. Cluster-randomized, controlled trial of computer-based decision support for selecting long-term anti-thrombotic therapy after acute ischaemic stroke.

    PubMed

    Weir, C J; Lees, K R; MacWalter, R S; Muir, K W; Wallesch, C-W; McLelland, E V; Hendry, A

    2003-02-01

    Identifying the appropriate long-term anti-thrombotic therapy following acute ischaemic stroke is a challenging area in which computer-based decision support may provide assistance. To evaluate the influence on prescribing practice of a computer-based decision support system (CDSS) that provided patient-specific estimates of the expected ischaemic and haemorrhagic vascular event rates under each potential anti-thrombotic therapy. Cluster-randomized controlled trial. We recruited patients who presented for a first investigation of ischaemic stroke or TIA symptoms, excluding those with a poor prognosis or major contraindication to anticoagulation. After observation of routine prescribing practice (6 months) in each hospital, centres were randomized for 6 months to either control (routine practice observed) or intervention (practice observed while the CDSS provided patient-specific information). We compared, between control and intervention centres, the risk reduction (estimated by the CDSS) in ischaemic and haemorrhagic vascular events achieved by long-term anti-thrombotic therapy, and the proportions of subjects prescribed the optimal therapy identified by the CDSS. Sixteen hospitals recruited 1952 subjects. When the CDSS provided information, the mean relative risk reduction attained by prescribing increased by 2.7 percentage units (95%CI -0.3 to 5.7) and the odds ratio for the optimal therapy being prescribed was 1.32 (0.83 to 1.80). Some 55% (5/9) of clinicians believed the CDSS had influenced their prescribing. Cluster-randomized trials provide excellent frameworks for evaluating novel clinical management methods. Our CDSS was feasible to implement and acceptable to clinicians, but did not substantially influence prescribing practice for anti-thrombotic drugs after acute ischaemic stroke.

  11. Modest blood pressure reduction with valsartan in acute ischemic stroke: a prospective, randomized, open-label, blinded-end-point trial.

    PubMed

    Oh, Mi Sun; Yu, Kyung-Ho; Hong, Keun-Sik; Kang, Dong-Wha; Park, Jong-Moo; Bae, Hee-Joon; Koo, Jaseong; Lee, Juneyoung; Lee, Byung-Chul

    2015-07-01

    To assess the efficacy and safety of modest blood pressure (BP) reduction with valsartan within 48 h after symptom onset in patients with acute ischemic stroke and high BP. This was a multicenter, prospective, randomized, open-label, blinded-end-point trial. A total of 393 subjects were recruited at 28 centers and then randomly assigned in a 1:1 ratio to receive valsartan (n = 195) or no treatment (n = 198) for seven-days after presentation. The primary outcome was death or dependency, defined as a score of 3-6 on the modified Rankin Scale (mRS) at 90 days after symptom onset. Early neurological deterioration (END) within seven-days and 90-day major vascular events were also assessed. There were 372 patients who completed the 90-day follow-up. The valsartan group had 46 of 187 patients (24·6%) with a 90-day mRS 3-6, compared with 42 of 185 patients (22·6%) in the control group (odds ratio [OR], 1·11; 95% confidence interval [CI], 0·69-1·79; P = 0·667). The rate of major vascular events did not differ between groups (OR, 1·41; 95% CI, 0·44-4·49; P = 0·771). There was a significant increase of END in the valsartan group (OR, 2·43; 95% CI, 1·25-4·73; P = 0·008). Early reduction of BP with valsartan did not reduce death or dependency and major vascular events at 90 days, but increased the risk of END. © 2015 World Stroke Organization.

  12. Evidence Report: Risk of Acute Radiation Syndromes Due to Solar Particle Events

    NASA Technical Reports Server (NTRS)

    Carnell, Lisa; Blattnig, Steve; Hu, Shaowen; Huff, Janice; Kim, Myung-Hee; Norman, Ryan; Patel, Zarana; Simonsen, Lisa; Wu, Honglu

    2016-01-01

    Crew health and performance may be impacted by a major solar particle event (SPE), multiple SPEs, or the cumulative effect of galactic cosmic rays (GCR) and SPEs. Beyond low-Earth orbit, the protection of the Earth's magnetosphere is no longer available, such that increased shielding and protective mechanisms are necessary in order to prevent acute radiation sickness and impacts to mission success or crew survival. While operational monitoring and shielding are expected to minimize radiation exposures, there are EVA scenarios outside of low-Earth orbit where the risk of prodromal effects, including nausea, vomiting, anorexia, and fatigue, as well as skin injury and depletion of the blood-forming organs (BFO), may occur. There is a reasonable concern that a compromised immune system due to high skin doses from a SPE or due to synergistic space flight factors (e.g., microgravity) may lead to increased risk to the BFO. The primary data available at present are derived from analyses of medical patients and persons accidentally exposed to acute, high doses of low-linear energy transfer (LET) (or terrestrial) radiation. Data more specific to the space flight environment must be compiled to quantify the magnitude of increase of this risk and to develop appropriate protection strategies. In particular, information addressing the distinct differences between solar proton exposures and terrestrial exposure scenarios, including radiation quality, dose-rate effects, and non-uniform dose distributions, is required for accurate risk estimation.

  13. Protective Role for Antioxidants in Acute Kidney Disease

    PubMed Central

    Dennis, Joanne M.; Witting, Paul K.

    2017-01-01

    Acute kidney injury causes significant morbidity and mortality in the community and clinic. Various pathologies, including renal and cardiovascular disease, traumatic injury/rhabdomyolysis, sepsis, and nephrotoxicity, that cause acute kidney injury (AKI), induce general or regional decreases in renal blood flow. The ensuing renal hypoxia and ischemia promotes the formation of reactive oxygen species (ROS) such as superoxide radical anions, peroxides, and hydroxyl radicals, that can oxidatively damage biomolecules and membranes, and affect organelle function and induce renal tubule cell injury, inflammation, and vascular dysfunction. Acute kidney injury is associated with increased oxidative damage, and various endogenous and synthetic antioxidants that mitigate source and derived oxidants are beneficial in cell-based and animal studies. However, the benefit of synthetic antioxidant supplementation in human acute kidney injury and renal disease remains to be realized. The endogenous low-molecular weight, non-proteinaceous antioxidant, ascorbate (vitamin C), is a promising therapeutic in human renal injury in critical illness and nephrotoxicity. Ascorbate may exert significant protection by reducing reactive oxygen species and renal oxidative damage via its antioxidant activity, and/or by its non-antioxidant functions in maintaining hydroxylase and monooxygenase enzymes, and endothelium and vascular function. Ascorbate supplementation may be particularly important in renal injury patients with low vitamin C status. PMID:28686196

  14. Impaired vascular function in physically active premenopausal women with functional hypothalamic amenorrhea is associated with low shear stress and increased vascular tone.

    PubMed

    O'Donnell, Emma; Goodman, Jack M; Mak, Susanna; Harvey, Paula J

    2014-05-01

    Exercise-trained hypoestrogenic premenopausal women with functional hypothalamic amenorrhea (ExFHA) exhibit impaired endothelial function. The vascular effects of an acute bout of exercise, a potent nitric oxide stimulus, in these women are unknown. Three groups were studied: recreationally active ExFHA women (n = 12; 24.2 ± 1.2 years of age; mean ± SEM), and recreationally active (ExOv; n = 14; 23.5 ± 1.2 years of age) and sedentary (SedOv; n = 15; 23.1 ± 0.5 years of age) ovulatory eumenorrheic women. Calf blood flow (CBF) and brachial artery flow-mediated dilation (FMD) were evaluated using plethysmographic and ultrasound techniques, respectively, both before and 1 hour after 45 minutes of moderate-intensity exercise. Endothelium-independent dilation was assessed at baseline using glyceryl trinitrate. Calf vascular resistance (CVR) and brachial peak shear rate, as determined by the area under the curve (SRAUCpk), were also calculated. FMD and glyceryl trinitrate responses were lower (P < .05) in ExFHA (2.8% ± 0.4% and 11.6% ± 0.7%, respectively) than ExOv (8.8% ± 0.7% and 16.7% ± 1.3%) and SedOv (8.0% ± 0.5% and 17.1% ± 1.8%). SRAUCpk was also lower (P < .05) in ExFHA. Normalization of FMD for SRAUCpk (FMD/SRAUCpk) did not alter (P > .05) the findings. CBF was lower (P < .05) and CVR higher (P < .05) in ExFHA. After exercise, FMD and SRAUCpk were augmented (P < .05), but remained lower (P < .05), in ExFHA. FMD/SRAUCpk no longer differed (P > .05) between the groups. CBF in ExFHA was increased (P < .05) and CVR decreased (P < .05) to levels observed in ovulatory women. Acute dynamic exercise improves vascular function in ExFHA women. Although the role of estrogen deficiency per se is unclear, our findings suggest that low shear rate and increased vasoconstrictor tone may play a role in impaired basal vascular function in these women.

  15. Short- and long-term major cardiovascular adverse events in carotid artery interventions: a nationwide population-based cohort study in Taiwan.

    PubMed

    Tsai, Ming-Lung; Mao, Chun-Tai; Chen, Dong-Yi; Hsieh, I-Chang; Wen, Ming-Shien; Chen, Tien-Hsing

    2015-01-01

    Carotid artery stenosis is one of the leading causes of ischemic stroke. Carotid artery stenting has become well-established as an effective treatment option for carotid artery stenosis. For this study, we aimed to determine the efficacy and safety of carotid stenting in a population-based large cohort of patients by analyzing the Taiwan National Healthcare Insurance (NHI) database. 2,849 patients who received carotid artery stents in the NHI database from 2004 to 2010 were identified. We analyzed the risk factors of outcomes including major adverse cardiovascular events including death, acute myocardial infarction, and cerebral vascular accidents at 30 days, 1 year, and overall period and further evaluated cause of death after carotid artery stenting. The periprocedural stroke rate was 2.7% and the recurrent stroke rate for the overall follow-up period was 20.3%. Male, diabetes mellitus, and heart failure were significant risk factors for overall recurrent stroke (Hazard Ratio (HR) = 1.35, p = 0.006; HR = 1.23, p = 0.014; HR = 1.61, p < 0.001, respectively). The periprocedural acute myocardial infarction rate was 0.3%. Age and Diabetes mellitus were the significant factors to predict periprocedural myocardial infarction (HR = 3.06, p = 0.019; HR = 1.68, p < 0.001, respectively). Periprocedural and overall mortality rates were 1.9% and 17.3%, respectively. The most significant periprocedural mortality risk factor was acute renal failure. Age, diabetes mellitus, acute or chronic renal failure, heart failure, liver disease, and malignancy were factors correlated to the overall period mortality. Periprocedural acute renal failure significantly increased the mortality rate and the number of major adverse cardiovascular events, and the predict power persisted more than one year after the procedure. Age and diabetes mellitus were significant risk factors to predict acute myocardial infarction after carotid artery stenting.

  16. Descriptive study of relationship between cardio-ankle vascular index and biomarkers in vascular-related diseases.

    PubMed

    Liu, Jinbo; Liu, Huan; Zhao, Hongwei; Shang, Guangyun; Zhou, Yingyan; Li, Lihong; Wang, Hongyu

    2017-01-01

    Cardio-ankle vascular index (CAVI) was supposed to be an independent predictor for vascular-related events. Biomarkers such as homocysteine (Hcy), N-terminal pro-brain natriuretic peptide (NT-proBNP), and urine albumin(microalbumin) (UAE) have involved the pathophysiological development of arteriosclerosis. The present study was to investigate relationship between CAVI and biomarkers in vascular-related diseases. A total of 656 subjects (M/F 272/384) from department of Vascular Medicine were enrolled into our study. They were divided into four groups according to the numbers of suffered diseases, healthy group (group 0: subjects without diseases of hypertension, diabetes mellitus (DM), coronary heart disease (CHD); n = 186), group 1 (with one of diseases of hypertension, CHD, DM; n = 237), group 2 (with two of diseases of hypertension, CHD, DM; n = 174), and group 3 (with all diseases of hypertension, CHD, DM; n = 59). CAVI was measured by VS-1000 apparatus. CAVI was increasing with increasing numbers of suffered vascular-related diseases. Similar results were found in the parameters of biomarkers such as Hcy, log NT-ProBNP, and log UAE. There were positive correlation between log NT-proBNP, Hcy, log UAE, and CAVI in the entire study group and nonhealthy group. Positive correlation between log UAE and CAVI were found in the entire study group after adjusting for age, body mass index (BMI), blood pressure, uric acid, and lipids. Multivariate analysis showed that log UAE was an independent associating factor of CAVI in all subjects. CAVI was significantly higher in subjects with hypertension, CHD, and DM. There was correlation between arterial stiffness and biomarkers such as NT-proBNP, Hcy, and UAE.

  17. The FReedom from Ischemic Events-New Dimensions for Survival (FRIENDS) registry: design of a prospective cohort study of patients with advanced peripheral artery disease.

    PubMed

    Keo, Hong H; Duval, Sue; Baumgartner, Iris; Oldenburg, Niki C; Jaff, Michael R; Goldman, JoAnne; Peacock, James M; Tretinyak, Alexander S; Henry, Timothy D; Luepker, Russell V; Hirsch, Alan T

    2013-12-19

    Advanced lower extremity peripheral artery disease (PAD), whether presenting as acute limb ischemia (ALI) or chronic critical limb ischemia (CLI), is associated with high rates of cardiovascular ischemic events, amputation, and death. Past research has focused on strategies of revascularization, but few data are available that prospectively evaluate the impact of key process of care factors (spanning pre-admission, acute hospitalization, and post-discharge) that might contribute to improving short and long-term health outcomes. The FRIENDS registry is designed to prospectively evaluate a range of patient and health system care delivery factors that might serve as future targets for efforts to improve limb and systemic outcomes for patients with ALI or CLI. This hypothesis-driven registry was designed to evaluate the contributions of: (i) pre-hospital limb ischemia symptom duration, (ii) use of leg revascularization strategies, and (iii) use of risk-reduction pharmacotherapies, as pre-specified factors that may affect amputation-free survival. Sequential patients would be included at an index "vascular specialist-defined" ALI or CLI episode, and patients excluded only for non-vascular etiologies of limb threat. Data including baseline demographics, functional status, co-morbidities, pre-hospital time segments, and use of medical therapies; hospital-based use of revascularization strategies, time segments, and pharmacotherapies; and rates of systemic ischemic events (e.g., myocardial infarction, stroke, hospitalization, and death) and limb ischemic events (e.g., hospitalization for revascularization or amputation) will be recorded during a minimum of one year follow-up. The FRIENDS registry is designed to evaluate the potential impact of key factors that may contribute to adverse outcomes for patients with ALI or CLI. Definition of new "health system-based" therapeutic targets could then become the focus of future interventional clinical trials for individuals with

  18. Intragraft vascular occlusive sickle crisis with early renal allograft loss in occult sickle cell trait.

    PubMed

    Kim, Lisa; Garfinkel, Marc R; Chang, Anthony; Kadambi, Pradeep V; Meehan, Shane M

    2011-07-01

    Early renal allograft failure due to sickle cell trait is rare. We present clinical and pathologic findings in 2 cases of early renal allograft failure associated with renal vein thrombosis and extensive erythrocyte sickling. Hemoglobin AS was identified in retrospect. In case 1, a 41-year-old female recipient of a deceased donor renal transplant developed abdominal pain and acute allograft failure on day 16, necessitating immediate nephrectomy. In case 2, the transplanted kidney in a 58-year-old female recipient was noted to be mottled blue within minutes of reperfusion. At 24 hours, the patient was oliguric; and the graft was removed. Transplant nephrectomies had diffuse enlargement with diffuse, nonhemorrhagic, cortical, and medullary necrosis. Extensive sickle vascular occlusion was evident in renal vein branches; interlobar, interlobular, and arcuate veins; vasa recta; and peritubular capillaries. The renal arteries had sickle vascular occlusion in case 1. Glomeruli had only focal sickle vascular occlusion. The erythrocytes in sickle vascular occlusion had abundant cytoplasmic filaments by electron microscopy. Acute rejection was not identified in either case. Protein C and S levels, factor V Leiden, and lupus anticoagulant assays were within normal limits. Hemoglobin analysis revealed hemoglobin S of 21.8% and 25.6%, respectively. Renal allograft necrosis with intragraft sickle crisis, characterized by extensive vascular occlusive erythrocyte sickling and prominent renal vein thrombosis, was observed in 2 patients with sickle cell trait. Occult sickle cell trait may be a risk factor for early renal allograft loss. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Possible influence of solar extreme events and related geomagnetic disturbances on human cardio-vascular state: Results of collaborative Bulgarian-Azerbaijani studies

    NASA Astrophysics Data System (ADS)

    Dimitrova, S.; Mustafa, F. R.; Stoilova, I.; Babayev, E. S.; Kazimov, E. A.

    2009-02-01

    This collaborative study is based on the analysis and comparison of results of coordinated experimental investigations conducted in Bulgaria and Azerbaijan for revealing a possible influence of solar activity changes and related geomagnetic activity variations on the human cardio-vascular state. Arterial blood pressure and heart rate of 86 healthy volunteers were measured on working days during a period of comparatively high solar and geomagnetic activity (2799 measurements in autumn 2001 and spring 2002) in Sofia. Daily experimental investigations of parameters of cardio-vascular health state were performed in Azerbaijan with a permanent group of examined persons. Heart rate and electrocardiograms were digitally registered (in total 1532 records) for seven functionally healthy persons on working days and Saturdays, in the Laboratory of Heliobiology at the Medical Center INAM in Baku, from 15.07.2006 to 13.11.2007. Obtained digital recordings were subjected to medical, statistical and spectral analyses. Special attention was paid to effects of solar extreme events, particularly those of November 2001 and December 2006. The statistical method of the analysis of variance (ANOVA) and post hoc analysis were applied to check the significance of the influence of geomagnetic activity on the cardio-vascular parameters under consideration. Results revealed statistically significant increments for the mean systolic and diastolic blood pressure values of the group with geomagnetic activity increase. Arterial blood pressure values started increasing two days prior to geomagnetic storms and kept their high values up to two days after the storms. Heart rate reaction was ambiguous and not significant for healthy persons examined (for both groups) under conditions with geomagnetic activity changes. It is concluded that heart rate for healthy persons at middle latitudes can be considered as a more stable physiological parameter which is not so sensitive to environmental changes

  20. The pharmacokinetics and clinical efficacy of AVP-825: a potential advancement for acute treatment of migraine.

    PubMed

    Cady, Roger

    2015-01-01

    Oral triptans have dominated the prescription market for acute treatment of migraine for nearly 25 years. Today, patients often express dissatisfaction with prescribed acute treatment in part because they do not have confidence that the therapy will provide consistent efficacy over time. Major limitations to sustained successful use of oral triptans are their relatively slow onset of meaningful clinical benefit and variable absorption/efficacy due to impaired gastrointestinal function during migraine. AVP-825, a new intranasal delivery system for sumatriptan , may be an effective alternative to oral triptans. This article reviews AVP-825, which deposits low-dose sumatriptan powder deep into the vascular mucosa of the posterior nose, allowing rapid absorption of drug into the systemic circulation. Studies suggest that AVP-825 is a highly effective, well-tolerated acute treatment for episodic migraine. Oral triptans are limited in providing effective patient-centered outcomes to migraine patients. Failed or suboptimal abortive treatment of migraine is a major driver of migraine chronification and increases in healthcare costs. AVP-825 is an easy to use, novel, breath-powered intranasal delivery system that provides early onset of efficacy with low systemic drug exposure and few triptan-associated adverse events. AVP-825 will be a welcomed therapeutic tool for the acute treatment of migraine.

  1. KLF2 and KLF4 control endothelial identity and vascular integrity

    PubMed Central

    Sangwung, Panjamaporn; Zhou, Guangjin; Nayak, Lalitha; Chan, E. Ricky; Kang, Dong-Won; Zhang, Rongli; Lu, Yuan; Sugi, Keiki; Fujioka, Hisashi; Shi, Hong; Lapping, Stephanie D.; Ghosh, Chandra C.; Higgins, Sarah J.; Parikh, Samir M.; Jain, Mukesh K.

    2017-01-01

    Maintenance of vascular integrity in the adult animal is needed for survival, and it is critically dependent on the endothelial lining, which controls barrier function, blood fluidity, and flow dynamics. However, nodal regulators that coordinate endothelial identity and function in the adult animal remain poorly characterized. Here, we show that endothelial KLF2 and KLF4 control a large segment of the endothelial transcriptome, thereby affecting virtually all key endothelial functions. Inducible endothelial-specific deletion of Klf2 and/or Klf4 reveals that a single allele of either gene is sufficient for survival, but absence of both (EC-DKO) results in acute death from myocardial infarction, heart failure, and stroke. EC-DKO animals exhibit profound compromise in vascular integrity and profound dysregulation of the coagulation system. Collectively, these studies establish an absolute requirement for KLF2/4 for maintenance of endothelial and vascular integrity in the adult animal. PMID:28239661

  2. Effects of cranberry juice consumption on vascular function in patients with coronary artery disease

    USDA-ARS?s Scientific Manuscript database

    Cranberry juice contains polyphenolic compounds that could improve endothelial function and reduce cardiovascular disease risk. The objective was to examine the effects of cranberry juice on vascular function in subjects with coronary artery disease. We completed an acute pilot study with no placebo...

  3. [Ultrasonography in acute pelvic pain].

    PubMed

    Kupesić, Sanja; Aksamija, Alenka; Vucić, Niksa; Tripalo, Ana; Kurjak, Asim

    2002-01-01

    accurate diagnosis of this entity since it enables differentiation between acute and chronic stages based on analysis of the vascular resistance. Hemorrhagic ovarian cysts may be presented by variety of ultrasound findings since intracystic echoes depend upon the quality and quantity of the blood clots. Color Doppler investigation demonstrates moderate to low vascular resistance typical of luteal flow. Leiomyomas undergoing degenerative changes are another cause of acute pelvic pain commonly present in patients of reproductive age. Color flow detects regularly separated vessels at the periphery of the leiomyoma, which exhibit moderate vascular resistance. Although the classic symptom of endometriosis is chronic pelvic pain, in some patients acute pelvic pain does occur. Most of these patients demonstrate an endometrioma or "chocolate" cyst containing diffuse carpet-like echoes. Sometimes, solid components may indicate even ovarian malignancy, but if color Doppler ultrasound is applied it is less likely to obtain false positive results. One should be aware that pericystic and/or hillar type of ovarian endometrioma vascularization facilitate correct recognition of this entity. Pelvic congestion syndrome is another condition that can cause an attack of acute pelvic pain. It is usually consequence of dilatation of venous plexuses, arteries or both systems. By switching color Doppler gynecologist can differentiate pelvic congestion syndrome from multilocular cysts, pelvic inflammatory disease or adenomyosis. Ovarian vein thrombosis is a potentially fatal disorder occurring most often in the early postpartal period. Hypercoagulability, infection and stasis are main etiologic factors, and transvaginal color Doppler ultrasound is an excellent diagnostic tool to diagnose it. Acute pelvic pain may occur even in normal intrauterine pregnancy. This may be explained by hormonal changes, rapid growth of the uterus and increased blood flow. Ultrasound is mandatory for distinguishing

  4. Vascular alterations in PDAPP mice after anti-Aβ immunotherapy: Implications for amyloid-related imaging abnormalities.

    PubMed

    Zago, Wagner; Schroeter, Sally; Guido, Teresa; Khan, Karen; Seubert, Peter; Yednock, Ted; Schenk, Dale; Gregg, Keith M; Games, Dora; Bard, Frédérique; Kinney, Gene G

    2013-10-01

    Clinical studies of β-amyloid (Aβ) immunotherapy in Alzheimer's disease (AD) patients have demonstrated reduction of central Aβ plaque by positron emission tomography (PET) imaging and the appearance of amyloid-related imaging abnormalities (ARIA). To better understand the relationship between ARIA and the pathophysiology of AD, we undertook a series of studies in PDAPP mice evaluating vascular alterations in the context of central Aβ pathology and after anti-Aβ immunotherapy. We analyzed PDAPP mice treated with either 3 mg/kg/week of 3D6, the murine form of bapineuzumab, or isotype control antibodies for periods ranging from 1 to 36 weeks and evaluated the vascular alterations in the context of Aβ pathology and after anti-Aβ immunotherapy. The number of mice in each treatment group ranged from 26 to 39 and a total of 345 animals were analyzed. The central vasculature displayed morphological abnormalities associated with vascular Aβ deposits. Treatment with 3D6 antibody induced clearance of vascular Aβ that was spatially and temporally associated with a transient increase in microhemorrhage and in capillary Aβ deposition. Microhemorrhage resolved over a time period that was associated with a recovery of vascular morphology and a decrease in capillary Aβ accumulation. These data suggest that vascular leakage events, such as microhemorrhage, may be related to the removal of vascular Aβ. With continued treatment, this initial susceptibility period is followed by restoration of vascular morphology and reduced vulnerability to further vascular leakage events. The data collectively suggested a vascular amyloid clearance model of ARIA, which accounts for the currently known risk factors for the incidence of ARIA in clinical studies. Copyright © 2013. Published by Elsevier Inc.

  5. Hypertonic Saline Reduces Vascular Leakage in a Mouse Model of Severe Dengue

    PubMed Central

    Tan, Kar Wai; Angeli, Veronique; Moochhala, Shabbir; Ooi, Eng Eong; Alonso, Sylvie

    2013-01-01

    Dengue (DEN) is a mosquito-borne viral disease and represents a serious public health threat and an economical burden throughout the tropics. Dengue clinical manifestations range from mild acute febrile illness to severe DEN hemorrhagic fever/DEN shock syndrome (DHF/DSS). Currently, resuscitation with large volumes of isotonic fluid remains the gold standard of care for DEN patients who develop vascular leakage and shock. Here, we investigated the ability of small volume of hypertonic saline (HTS) suspensions to control vascular permeability in a mouse model of severe DEN associated with vascular leakage. Several HTS treatment regimens were considered and our results indicated that a single bolus of 7.5% NaCl at 4 mL per kg of body weight administered at the onset of detectable vascular leakage rapidly and significantly reduced vascular leak for several days after injection. This transient reduction of vascular leakage correlated with reduced intestine and liver damage with restoration of the hepatic functions, and resulted in delayed death of the infected animals. Mechanistically, we showed that HTS did not directly impact on the viral titers but resulted in lower immune cells counts and decreased systemic levels of soluble mediators involved in vascular permeability. In addition, we demonstrated that neutrophils do not play a critical role in DEN-associated vascular leakage and that the therapeutic effect of HTS is not mediated by its impact on the neutrophil counts. Together our data indicate that HTS treatment can transiently but rapidly reduce dengue-associated vascular leakage, and support the findings of a recent clinical trial which evaluated the efficacy of a hypertonic suspension to impact on vascular permeability in DSS children. PMID:23637867

  6. Geospatial relationships of air pollution and acute asthma events across the Detroit-Windsor international border: study design and preliminary results.

    PubMed

    Lemke, Lawrence D; Lamerato, Lois E; Xu, Xiaohong; Booza, Jason C; Reiners, John J; Raymond Iii, Delbert M; Villeneuve, Paul J; Lavigne, Eric; Larkin, Dana; Krouse, Helene J

    2014-07-01

    The Geospatial Determinants of Health Outcomes Consortium (GeoDHOC) study investigated ambient air quality across the international border between Detroit, Michigan, USA and Windsor, Ontario, Canada and its association with acute asthma events in 5- to 89-year-old residents of these cities. NO2, SO2, and volatile organic compounds (VOCs) were measured at 100 sites, and particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) at 50 sites during two 2-week sampling periods in 2008 and 2009. Acute asthma event rates across neighborhoods in each city were calculated using emergency room visits and hospitalizations and standardized to the overall age and gender distribution of the population in the two cities combined. Results demonstrate that intra-urban air quality variations are related to adverse respiratory events in both cities. Annual 2008 asthma rates exhibited statistically significant positive correlations with total VOCs and total benzene, toluene, ethylbenzene and xylene (BTEX) at 5-digit zip code scale spatial resolution in Detroit. In Windsor, NO2, VOCs, and PM10 concentrations correlated positively with 2008 asthma rates at a similar 3-digit postal forward sortation area scale. The study is limited by its coarse temporal resolution (comparing relatively short term air quality measurements to annual asthma health data) and interpretation of findings is complicated by contrasts in population demographics and health-care delivery systems in Detroit and Windsor.

  7. Unintended inhalation of nitric oxide by contamination of compressed air: physiologic effects and interference with intended nitric oxide inhalation in acute lung injury.

    PubMed

    Benzing, A; Loop, T; Mols, G; Geiger, K

    1999-10-01

    Compressed air from a hospital's central gas supply may contain nitric oxide as a result of air pollution. Inhaled nitric oxide may increase arterial oxygen tension and decrease pulmonary vascular resistance in patients with acute lung injury and acute respiratory distress syndrome. Therefore, the authors wanted to determine whether unintentional nitric oxide inhalation by contamination of compressed air influences arterial oxygen tension and pulmonary vascular resistance and interferes with the therapeutic use of nitric oxide. Nitric oxide concentrations in the compressed air of a university hospital were measured continuously by chemiluminescence during two periods (4 and 2 weeks). The effects of unintended nitric oxide inhalation on arterial oxygen tension (n = 15) and on pulmonary vascular resistance (n = 9) were measured in patients with acute lung injury and acute respiratory distress syndrome by changing the source of compressed air of the ventilator from the hospital's central gas supply to a nitric oxide-free gas tank containing compressed air. In five of these patients, the effects of an additional inhalation of 5 ppm nitric oxide were evaluated. During working days, compressed air of the hospital's central gas supply contained clinically effective nitric oxide concentrations (> 80 parts per billion) during 40% of the time. Change to gas tank-supplied nitric oxide-free compressed air decreased the arterial oxygen tension by 10% and increased pulmonary vascular resistance by 13%. The addition of 5 ppm nitric oxide had a minimal effect on arterial oxygen tension and pulmonary vascular resistance when added to hospital-supplied compressed air but improved both when added to tank-supplied compressed air. Unintended inhalation of nitric oxide increases arterial oxygen tension and decreases pulmonary vascular resistance in patients with acute lung injury and acute respiratory distress syndrome. The unintended nitric oxide inhalation interferes with the

  8. [Management of Acute Type A Dissection Complicated with Acute Mesenteric Ischemia].

    PubMed

    Abe, Tomonobu; Usui, Akihiko

    2017-07-01

    Acute mesenteric ischemia as malperfusion syndrome associated with acute aortic dissection is a difficult situation. The incidence is approximately 3~4% in acute type A dissection. Traditionally, most of these patients underwent immediate simple central aortic repair expecting that mesenteric artery obstruction and intestinal ischemia would be resolved by simple central aortic repair. However, short term mortality has been reported very high in this strategy. With the aid of rapidly progressing imaging techniques and newer endovascular repair techniques, results seem to be improving in recent years. Newer management strategy include aggressive and patient specific revascularization to the mesenteric arteries, delayed central aortic repair, and meticulous intensive care. Diagnosis and management of this condition require high level of expertise. Cardiac surgeons, vascular surgeons, interventional radiologists, gastroenterologists, general surgeons, anesthesiologists, intensivists must corporate to save these patients' lives. Since this is a relatively rare condition, scientific evidence is insufficient to make robust recommendations. Further studies are warranted.

  9. [Value of DC and DRs in prediction of cardiovascular events in acute myocardial infarction patients].

    PubMed

    Gao, L; Chen, Y D; Shi, Y J; Xue, H; Wang, J L

    2016-05-24

    To investigate the value of deceleration capacity of rate (DC) and heart rate deceleration runs(DRs) in predicting cardiovascular events in patient with acute myocardial infarction (AMI). This study included 166 patients with AMI, who underwent ECG with sinus rhythm.These patients were followed-up for major adverse cardiac events (MACE). The receiver operating characteristic curve (ROC) was drawn to determine the best values for estimating the MACE. The mean follow-up time was (20.5±2.8) months, with 13 cases of cardiac death.There was statistically significant difference of DC, DRs and standard diviation of NN intervals(SDNN-24) between the death group and survival group.The area under the curve (AUC) of DC, DR4 and DR8 were larger than SDNN-24 (0.874, 0.804 vs 0.727). The values of DC, DR2, DR4 and root mean square of the successive differences(RMSSD) in the group of patients who underwent cardiac adverse events were smaller than the group of patients who didn't, and the AUC of DC was slightly higher than that of RMSSD. DC and DRs have important predictive value for cardiac death and MACE and can screen high-risk patients in patients with AMI.

  10. Is bioresorbable vascular scaffold acute recoil affected by baseline renal function and scaffold selection?

    PubMed

    Gunes, Haci Murat; Yılmaz, Filiz Kizilirmak; Gokdeniz, Tayyar; Demir, Gultekin Gunhan; Guler, Ekrem; Guler, Gamze Babur; Karaca, Oğuz; Cakal, Beytullah; İbişoğlu, Ersin; Boztosun, Bilal

    2016-12-01

    The aim of the present study was to investigate the relationship between glomerular filtration rate (GFR) and acute post-scaffold recoil (PSR) in patients undergoing bioresorbable scaffold (BVS) implantation. We included 130 patients who underwent everolimus-eluting BVS device (Absorb BVS; Abbott Vascular, Santa Clara, CA, USA) or the novolimus-eluting BVS device (Elixir Medical Corporation) implantations for single or multi-vessel disease. Clinical, angiographic variables and procedural characteristics were defined and pre-procedural GFR was calculated for each patient. Post-procedural angiographic parameters of each patient were analyzed. Primary objective of the study was to evaluate the effect of GFR on angiographic outcomes after BVS implantation while secondary objective was to compare post-procedural angiographic results between the two BVS device groups. Baseline clinical characteristics and angiographic parameters were similar between the two BVS groups. Post-procedural angiographic analysis revealed significantly lower PSR in the DESolve group than the Absorb group (0.10±0.04 vs. 0.13±0.05, p: 0.003). When PSR in the whole study population was evaluated, it was positively correlated with age, tortuosity , calcification and PBR as there was a negative correlation between GFR. Besides GFR were found to be independent predictors for PSR in all groups and the whole study population. In patients undergoing BVS implantation, pre-procedural low GFR is associated with increased post-procedural PSR. Calcification, age, PBR, dyslipidemia and tortuosity are other independent risk factors for PSR. DESolve has lower PSR when compared with Absorb. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Effects of acute and chronic cilazapril treatment in spontaneously hypertensive rats

    PubMed Central

    Fischli, W.; Hefti, F.; Clozel, J.-P.

    1989-01-01

    1 The effects of acute and chronic treatment with cilazapril, a new ACE inhibitor, on peripheral vasculature and renal excretory function were assessed in spontaneously hypertensive rats. Regional blood flow and cardiac output were measured by the radio-active microspheres technique. 2 Acute treatment (3 mg kg-1 intravenously) reduced mean arterial blood pressure from 171 ± 7 to 140 241 ± 7 mm Hg (P < 0.001), chronic treatment (1 × 10 mg kg-1 day-1 orally for 9 weeks) from 191 ± 5 to 122 ± 3 mm Hg P < 0.001). With both kinds of treatments cardiac output was unchanged. Heart rate was slightly decreased (-9%, P < 0.05) with chronic treatment. Acutely, the main effect of cilazapril was a decrease of the renal vascular resistance (-41%, P < 0.001) associated with an increase of the fraction of the cardiac output distributed to the kidney (+46%, P < 0.001). Chronically, cilazapril decreased regional vascular resistance in most of the peripheral vascular beds except the heart. 3 With a high dose of cilazapril (10 mg kg-1 orally) both acute and chronic treatment increased diuresis (+107% and +92%, P < 0.001) and natriuresis (+124% and +111%, P < 0.001) with a slight increase in kaliuresis. However, with a low dose (1 mg kg-1 orally) the kidneys responded only to chronic treatment. 4 It is concluded that chronic treatment with cilazapril decreases arterial blood pressure more than acute treatment. This effect seems to be due to a greater peripheral vasodilation. In addition, diuretic and natriuretic effects of cilazapril probably contribute to blood pressure reduction. PMID:2527529

  12. Hemoglobin induced lung vascular oxidation, inflammation, and remodeling contributes to the progression of hypoxic pulmonary hypertension and is attenuated in rats with repeat dose haptoglobin administration

    PubMed Central

    Baek, Jin Hyen; Hassell, Kathryn; Nuss, Rachelle; Eigenberger, Paul; Lisk, Christina; Loomis, Zoe; Maltzahn, Joanne; Stenmark, Kurt R; Nozik-Grayck, Eva

    2015-01-01

    Objective Haptoglobin (Hp) is an approved treatment in Japan with indications for trauma, burns and massive transfusion related hemolysis. Additional case reports suggest uses in other acute hemolytic events that lead to acute kidney injury. However, Hp's protective effects on the pulmonary vasculature have not been evaluated within the context of mitigating the consequences of chronic hemoglobin (Hb) exposure in the progression of pulmonary hypertension (PH) secondary to hemolytic diseases. This study was performed to assess the utility of chronic Hp therapy in a preclinical model of Hb and hypoxia mediated PH. Approach and results Rats were simultaneously exposed to chronic Hb-infusion (35 mg per day) and hypobaric hypoxia for five weeks in the presence or absence of Hp treatment (90 mg/kg twice a week). Hp inhibited the Hb plus hypoxia-mediated non-heme iron accumulation in lung and heart tissue, pulmonary vascular inflammation and resistance, and right ventricular hypertrophy, which suggest a positive impact on impeding the progression of PH. In addition, Hp therapy was associated with a reduction in critical mediators of PH, including lung adventitial macrophage population and endothelial ICAM-1 expression. Conclusions By preventing Hb-mediated pathology, Hp infusions: (1) demonstrate a critical role for Hb in vascular remodeling associated with hypoxia; and (2) suggest a novel therapy for chronic hemolysis associated PH. PMID:25656991

  13. Hemoglobin-induced lung vascular oxidation, inflammation, and remodeling contribute to the progression of hypoxic pulmonary hypertension and is attenuated in rats with repeated-dose haptoglobin administration.

    PubMed

    Irwin, David C; Baek, Jin Hyen; Hassell, Kathryn; Nuss, Rachelle; Eigenberger, Paul; Lisk, Christina; Loomis, Zoe; Maltzahn, Joanne; Stenmark, Kurt R; Nozik-Grayck, Eva; Buehler, Paul W

    2015-05-01

    Haptoglobin (Hp) is an approved treatment in Japan for trauma, burns, and massive transfusion-related hemolysis. Additional case reports suggest uses in other acute hemolytic events that lead to acute kidney injury. However, Hp's protective effects on the pulmonary vasculature have not been evaluated within the context of mitigating the consequences of chronic hemoglobin (Hb) exposure in the progression of pulmonary hypertension (PH) secondary to hemolytic diseases. This study was performed to assess the utility of chronic Hp therapy in a preclinical model of Hb and hypoxia-mediated PH. Rats were simultaneously exposed to chronic Hb infusion (35 mg per day) and hypobaric hypoxia for 5 weeks in the presence or absence of Hp treatment (90 mg/kg twice a week). Hp inhibited the Hb plus hypoxia-mediated nonheme iron accumulation in lung and heart tissue, pulmonary vascular inflammation and resistance, and right-ventricular hypertrophy, which suggests a positive impact on impeding the progression of PH. In addition, Hp therapy was associated with a reduction in critical mediators of PH, including lung adventitial macrophage population and endothelial ICAM-1 expression. By preventing Hb-mediated pathology, Hp infusions: (1) demonstrate a critical role for Hb in vascular remodeling associated with hypoxia and (2) suggest a novel therapy for chronic hemolysis-associated PH. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. GSK-3Beta-Dependent Activation of GEF-H1/ROCK Signaling Promotes LPS-Induced Lung Vascular Endothelial Barrier Dysfunction and Acute Lung Injury.

    PubMed

    Yi, Lei; Huang, Xiaoqin; Guo, Feng; Zhou, Zengding; Chang, Mengling; Huan, Jingning

    2017-01-01

    The bacterial endotoxin or lipopolysaccharide (LPS) leads to the extensive vascular endothelial cells (EC) injury under septic conditions. Guanine nucleotide exchange factor-H1 (GEF-H1)/ROCK signaling not only involved in LPS-induced overexpression of pro-inflammatory mediator in ECs but also implicated in LPS-induced endothelial hyper-permeability. However, the mechanisms behind LPS-induced GEF-H1/ROCK signaling activation in the progress of EC injury remain incompletely understood. GEF-H1 localized on microtubules (MT) and is suppressed in its MT-bound state. MT disassembly promotes GEF-H1 release from MT and stimulates downstream ROCK-specific GEF activity. Since glycogen synthase kinase (GSK-3beta) participates in regulating MT dynamics under pathologic conditions, we examined the pivotal roles for GSK-3beta in modulating LPS-induced activation of GEF-H1/ROCK, increase of vascular endothelial permeability and severity of acute lung injury (ALI). In this study, we found that LPS induced human pulmonary endothelial cell (HPMEC) monolayers disruption accompanied by increase in GSK-3beta activity, activation of GEF-H1/ROCK signaling and decrease in beta-catenin and ZO-1 expression. Inhibition of GSK-3beta reduced HPMEC monolayers hyper-permeability and GEF-H1/ROCK activity in response to LPS. GSK-3beta/GEF-H1/ROCK signaling is implicated in regulating the expression of beta-catenin and ZO-1. In vivo , GSK-3beta inhibition attenuated LPS-induced activation of GEF-H1/ROCK pathway, lung edema and subsequent ALI. These findings present a new mechanism of GSK-3beta-dependent exacerbation of lung micro-vascular hyper-permeability and escalation of ALI via activation of GEF-H1/ROCK signaling and disruption of intracellular junctional proteins under septic condition.

  15. Recurrent acute transverse myelopathy: association with antiphospholipid antibody syndrome.

    PubMed

    Shaharao, Vijaya; Bartakke, Sandip; Muranjan, Mamta N; Bavdekar, Manisha S; Bavdekar, Sandeep B; Udani, Vrajesh P

    2004-06-01

    A seven-year-old boy presented with a second episode of acute transverse myelopathy. The first episode had responded dramatically to methylprednisolone. The manifestations of the second episode did not respond to methylprednisolone or IVIG. He showed persistently raised levels of antiphospholipid antibodies in the serum. Primary conditions like collagen vascular diseases, malignancy, exposure to drugs and HIV infection, which are known to be associated with the raised titers of these antibodies were ruled out clinically and by investigations. Recurrent transverse myelopathy is a rare event in childhood and reports of its association with Antiphospholipid Antibody Syndrome (APLAS) are scanty. The etiological role for these antibodies remains to be established. However, once the diagnosis is established, it may be prudent to treat the condition with agents and procedures to bring about a decrease in their titers. Long-term therapy to prevent thromboembolic complications of APLAS may also be instituted.

  16. Altered Arterial Stiffness and Subendocardial Viability Ratio in Young Healthy Light Smokers after Acute Exercise

    PubMed Central

    Doonan, Robert J.; Scheffler, Patrick; Yu, Alice; Egiziano, Giordano; Mutter, Andrew; Bacon, Simon; Carli, Franco; Daskalopoulos, Marios E.; Daskalopoulou, Stella S.

    2011-01-01

    Background Studies showed that long-standing smokers have stiffer arteries at rest. However, the effect of smoking on the ability of the vascular system to respond to increased demands (physical stress) has not been studied. The purpose of this study was to estimate the effect of smoking on arterial stiffness and subendocardial viability ratio, at rest and after acute exercise in young healthy individuals. Methods/Results Healthy light smokers (n = 24, pack-years = 2.9) and non-smokers (n = 53) underwent pulse wave analysis and carotid-femoral pulse wave velocity measurements at rest, and 2, 5, 10, and 15 minutes following an exercise test to exhaustion. Smokers were tested, 1) after 12h abstinence from smoking (chronic condition) and 2) immediately after smoking one cigarette (acute condition). At rest, chronic smokers had higher augmentation index and lower aortic pulse pressure than non-smokers, while subendocardial viability ratio was not significantly different. Acute smoking increased resting augmentation index and decreased subendocardial viability ratio compared with non-smokers, and decreased subendocardial viability ratio compared with the chronic condition. After exercise, subendocardial viability ratio was lower, and augmentation index and aortic pulse pressure were higher in non-smokers than smokers in the chronic and acute conditions. cfPWV rate of recovery of was greater in non-smokers than chronic smokers after exercise. Non-smokers were also able to achieve higher workloads than smokers in both conditions. Conclusion Chronic and acute smoking appears to diminish the vascular response to physical stress. This can be seen as an impaired ‘vascular reserve’ or a blunted ability of the blood vessels to accommodate the changes required to achieve higher workloads. These changes were noted before changes in arterial stiffness or subendocardial viability ratio occurred at rest. Even light smoking in young healthy individuals appears to have

  17. The ARTICO study: identification of patients at high risk of vascular recurrence after a first non-cardioembolic stroke.

    PubMed

    Serena, Joaquín; Segura, Tomás; Roquer, Jaume; García-Gil, María; Castillo, José

    2015-03-11

    About 20% of patients with a first ischaemic stroke will experience a new vascular event within the first year. The atherosclerotic burden, an indicator of the extension of atherosclerosis in a patient, has been associated with the risk of new cardiovascular events in the general population. However, no predictive models reliably identify groups at a high risk of recurrence. The ARTICO study prospectively analysed the predictive value for the risk of recurrence of specific atherosclerotic markers. The multicentre ARTICO study included 620 consecutive independent patients older than 60 years suffering from a first non-cardioembolic stroke. We analysed classical stroke risk factors; duplex study of supraaortic trunk including intima-media thickness (IMT) measurement; quantification of internal carotid (ICA) stenosis; number, morphology and surface characteristics of carotid plaques; ankle brachial index (ABI); and the presence of microalbuminuria. Patients were followed up at 6 and 12 months after inclusion. The primary end-point was death or major cardiovascular events. Any vascular event or death at 12 months occurred in 78 (13.8%) patients. In 40 (7.1%) of these the vascular event was a stroke recurrence. Weight, history of diabetes mellitus, history of symptomatic PAD, ABI <0.9 and significant ICA stenosis (>50%) were associated with a higher risk of vascular events on follow-up in the bivariate analysis. In the final Cox regression analysis, body mass index (BMI), systolic blood pressure, history of diabetes mellitus, symptomatic PAD (HR, 2.76; 95% CI, 1.10-6.95; p=0.03), and particularly patients with both ICA stenosis >50% and PAD (HR 4.52; 95% CI, 2.14-9.53; p<0.001) were independently associated with an increased risk of vascular events. Neither isolated ICA stenosis >50% nor isolated abnormal ABI remained associated with an increased risk of recurrence in comparison with the whole population. Symptomatic PAD identifies a high risk group of vascular

  18. Vascular Anomalies (Part I): Classification and Diagnostics of Vascular Anomalies.

    PubMed

    Sadick, Maliha; Müller-Wille, René; Wildgruber, Moritz; Wohlgemuth, Walter A

    2018-06-06

    Vascular anomalies are a diagnostic and therapeutic challenge. They require dedicated interdisciplinary management. Optimal patient care relies on integral medical evaluation and a classification system established by experts in the field, to provide a better understanding of these complex vascular entities.  A dedicated classification system according to the International Society for the Study of Vascular Anomalies (ISSVA) and the German Interdisciplinary Society of Vascular Anomalies (DiGGefA) is presented. The vast spectrum of diagnostic modalities, ranging from ultrasound with color Doppler, conventional X-ray, CT with 4 D imaging and MRI as well as catheter angiography for appropriate assessment is discussed.  Congenital vascular anomalies are comprised of vascular tumors, based on endothelial cell proliferation and vascular malformations with underlying mesenchymal and angiogenetic disorder. Vascular tumors tend to regress with patient's age, vascular malformations increase in size and are subdivided into capillary, venous, lymphatic, arterio-venous and combined malformations, depending on their dominant vasculature. According to their appearance, venous malformations are the most common representative of vascular anomalies (70 %), followed by lymphatic malformations (12 %), arterio-venous malformations (8 %), combined malformation syndromes (6 %) and capillary malformations (4 %).  The aim is to provide an overview of the current classification system and diagnostic characterization of vascular anomalies in order to facilitate interdisciplinary management of vascular anomalies.   · Vascular anomalies are comprised of vascular tumors and vascular malformations, both considered to be rare diseases.. · Appropriate treatment depends on correct classification and diagnosis of vascular anomalies, which is based on established national and international classification systems, recommendations and guidelines.. · In the classification

  19. Oxidative stress and vascular inflammation in aging.

    PubMed

    El Assar, Mariam; Angulo, Javier; Rodríguez-Mañas, Leocadio

    2013-12-01

    Vascular aging, a determinant factor for cardiovascular disease and health status in the elderly, is now viewed as a modifiable risk factor. Impaired endothelial vasodilation is a early hallmark of arterial aging that precedes the clinical manifestations of vascular dysfunction, the first step to cardiovascular disease and influencing vascular outcomes in the elderly. Accordingly, the preservation of endothelial function is thought to be an essential determinant of healthy aging. With special attention on the effects of aging on the endothelial function, this review is focused on the two main mechanisms of aging-related endothelial dysfunction: oxidative stress and inflammation. Aging vasculature generates an excess of the reactive oxygen species (ROS), superoxide and hydrogen peroxide, that compromise the vasodilatory activity of nitric oxide (NO) and facilitate the formation of the deleterious radical, peroxynitrite. Main sources of ROS are mitochondrial respiratory chain and NADPH oxidases, although NOS uncoupling could also account for ROS generation. In addition, reduced antioxidant response mediated by erythroid-2-related factor-2 (Nrf2) and downregulation of mitochondrial manganese superoxide dismutase (SOD2) contributes to the establishment of chronic oxidative stress in aged vessels. This is accompanied by a chronic low-grade inflammatory phenotype that participates in defective endothelial vasodilation. The redox-sensitive transcription factor, nuclear factor-κB (NF-κB), is upregulated in vascular cells from old subjects and drives a proinflammatory shift that feedbacks oxidative stress. This chronic NF-κB activation is contributed by increased angiotensin-II signaling and downregulated sirtuins and precludes adequate cellular response to acute ROS generation. Interventions targeted to recover endogenous antioxidant capacity and cellular stress response rather than exogenous antioxidants could reverse oxidative stress-inflammation vicious cycle in

  20. Mediterranean-style diet and risk of ischemic stroke, myocardial infarction, and vascular death: the Northern Manhattan Study.

    PubMed

    Gardener, Hannah; Wright, Clinton B; Gu, Yian; Demmer, Ryan T; Boden-Albala, Bernadette; Elkind, Mitchell S V; Sacco, Ralph L; Scarmeas, Nikolaos

    2011-12-01

    A dietary pattern common in regions near the Mediterranean appears to reduce risk of all-cause mortality and ischemic heart disease. Data on blacks and Hispanics in the United States are lacking, and to our knowledge only one study has examined a Mediterranean-style diet (MeDi) in relation to stroke. In this study, we examined an MeDi in relation to vascular events. The Northern Manhattan Study is a population-based cohort to determine stroke incidence and risk factors (mean ± SD age of participants: 69 ± 10 y; 64% women; 55% Hispanic, 21% white, and 24% black). Diet was assessed at baseline by using a food-frequency questionnaire in 2568 participants. A higher score on a 0-9 scale represented increased adherence to an MeDi. The relation between the MeDi score and risk of ischemic stroke, myocardial infarction (MI), and vascular death was assessed with Cox models, with control for sociodemographic and vascular risk factors. The MeDi-score distribution was as follows: 0-2 (14%), 3 (17%), 4 (22%), 5 (22%), and 6-9 (25%). Over a mean follow-up of 9 y, 518 vascular events accrued (171 ischemic strokes, 133 MIs, and 314 vascular deaths). The MeDi score was inversely associated with risk of the composite outcome of ischemic stroke, MI, or vascular death (P-trend = 0.04) and with vascular death specifically (P-trend = 0.02). Moderate and high MeDi scores were marginally associated with decreased risk of MI. There was no association with ischemic stroke. Higher consumption of an MeDi was associated with decreased risk of vascular events. Results support the role of a diet rich in fruit, vegetables, whole grains, fish, and olive oil in the promotion of ideal cardiovascular health.

  1. Vascular risk factor burden and new-onset depression in the community.

    PubMed

    Adams, Shayna; Conner, Sarah; Himali, Jayandra J; Beiser, Alexa; Vasan, Ramachandran S; Seshadri, Sudha; Pase, Matthew P

    2018-06-01

    Depression is associated with an increased likelihood of cardiac events and stroke. We hypothesized that the vascular risk factor burden might itself predispose to both cardiovascular events and depression. Therefore, we examined whether aggregate scores of vascular risk factor burden were associated with the new-onset of depression in the community. We studied 2023 depression- and dementia-free Framingham Heart Study (Framingham, USA) Offspring participants who attended both examination cycles 7 (1998-2001) and 8 (2005-2008). The American Heart Association Ideal Cardiovascular Health metric and the Framingham stroke risk profile were calculated at exam seven. New-onset depression was adjudicated at examination cycle eight as antidepressant medication use or Centre for Epidemiologic Studies Depression Scale scores ≥16, after a mean follow-up of 6.6years (standard deviation=0.7). Of the 2023 participants, 269 (13%) developed new-onset depression. Following adjustments for age, sex, education, and the time interval between baseline and follow-up, the odds of new-onset depression decreased by 10% for each one-point increase in ideal cardiovascular health scores (Odds Ratio [OR], 0.90; 95% confidence interval [CI] 0.81-0.99) and increased by 4% for each percentage point increase in the Framingham stroke risk profile (OR, 1.04; CI, 1.00-1.07). Results were not explained by interim clinical stroke or cerebral white matter injury. In conclusion, vascular risk factor burden was associated with the new onset of depression. Shared vascular risk factors may contribute to the increased risk of cardiovascular events observed in persons with depression. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. A taurine-supplemented vegan diet may blunt the contribution of neutrophil activation to acute coronary events.

    PubMed

    McCarty, Mark F

    2004-01-01

    Neutrophils are activated in the coronary circulation during acute coronary events (unstable angina and myocardial infarction), often prior to the onset of ischemic damage. Moreover, neutrophils infiltrate coronary plaque in these circumstances, and may contribute to the rupture or erosion of this plaque, triggering thrombosis. Activated neutrophils secrete proteolytic enzymes in latent forms which are activated by the hypochlorous acid (HOCl) generated by myeloperoxidase. These phenomena may help to explain why an elevated white cell count has been found to be an independent coronary risk factor. Low-fat vegan diets can decrease circulating leukocytes--neutrophils and monocytes--possibly owing to down-regulation of systemic IGF-I activity. Thus, a relative neutropenia may contribute to the coronary protection afforded by such diets. However, vegetarian diets are devoid of taurine - the physiological antagonist of HOCl--and tissue levels of this nutrient are relatively low in vegetarians. Taurine has anti-atherosclerotic activity in animal models, possibly reflecting a role for macrophage-derived myeloperoxidase in the atherogenic process. Taurine also has platelet-stabilizing and anti-hypertensive effects that presumably could reduce coronary risk. Thus, it is proposed that a taurine-supplemented low-fat vegan diet represents a rational strategy for diminishing the contribution of activated neutrophils to acute coronary events; moreover, such a regimen would work in a number of other complementary ways to promote cardiovascular health. Moderate alcohol consumption, the well-tolerated drug pentoxifylline, and 5-lipoxygenase inhibitors--zileuton, boswellic acids, fish oil--may also have potential in this regard. Copyright 2004 Elsevier Ltd.

  3. Exploring ischemia-induced vascular lesions and potential pharmacological intervention strategies.

    PubMed

    Aliev, G; Obrenovich, M E; Seyidova, D; de la Torre, J C

    2005-01-01

    Structural changes in vessels under the influence of ischemia play an important role in the pathogenesis of many diseases, most important of which are stroke and myocardial infarction or myocardial insult. Over the years, information has been gathered, which implicate a role for ischemic vascular changes in the pathogenesis of crush-syndrome, atherosclerosis and other vascular diseases. When blood vessels are damaged they become unresponsive to a stimulus, which normally elicits vasodilatation and can lead to intraluminal thrombosis and ischemic events. The aim of this review is to explore the structural changes seen in vessels affected by ischemia reperfusion injury. With ischemia, the development of observable changes to vascular structure is multifactorial. One key factor is reperfusion ischemic injury. Moreover, the duration of the ischemic event is an important factor when determining both the prognosis and the type of morphological change that is observable in affected vessel walls. In this regard, the deleterious progression of blood flow impairment and its severity depends on the specific organ involved and the type of tissue affected. Further, there are regional differences within affected tissues and the degree of microvascular injury is well correlated with differences in the nature and severity of the ischemic event. Any method aimed at preventing and treating ischemic reperfusion injuries in vessels, based on these investigations, should likewise be able to decrease the early signs of brain, cerebrovascular and heart injury and preserve normal cellular architecture.

  4. Aldosterone Does Not Predict Cardiovascular Events Following Acute Coronary Syndrome in Patients Initially Without Heart Failure.

    PubMed

    Pitts, Reynaria; Gunzburger, Elise; Ballantyne, Christie M; Barter, Philip J; Kallend, David; Leiter, Lawrence A; Leitersdorf, Eran; Nicholls, Stephen J; Shah, Prediman K; Tardif, Jean-Claude; Olsson, Anders G; McMurray, John J V; Kittelson, John; Schwartz, Gregory G

    2017-01-10

    Aldosterone may have adverse effects in the myocardium and vasculature. Treatment with an aldosterone antagonist reduces cardiovascular risk in patients with acute myocardial infarction complicated by heart failure (HF) and left ventricular systolic dysfunction. However, most patients with acute coronary syndrome do not have advanced HF. Among such patients, it is unknown whether aldosterone predicts cardiovascular risk. To address this question, we examined data from the dal-OUTCOMES trial that compared the cholesteryl ester transfer protein inhibitor dalcetrapib with placebo, beginning 4 to 12 weeks after an index acute coronary syndrome. Patients with New York Heart Association class II (with LVEF <40%), III, or IV HF were excluded. Aldosterone was measured at randomization in 4073 patients. The primary outcome was a composite of coronary heart disease death, nonfatal myocardial infarction, stroke, hospitalization for unstable angina, or resuscitated cardiac arrest. Hospitalization for HF was a secondary endpoint. Over a median follow-up of 37 months, the primary outcome occurred in 366 patients (9.0%), and hospitalization for HF occurred in 72 patients (1.8%). There was no association between aldosterone and either the time to first occurrence of a primary outcome (hazard ratio for doubling of aldosterone 0.92, 95% confidence interval 0.78-1.09, P=0.34) or hospitalization for HF (hazard ratio 1.38, 95% CI 0.96-1.99, P=0.08) in Cox regression models adjusted for covariates. In patients with recent acute coronary syndrome but without advanced HF, aldosterone does not predict major cardiovascular events. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00658515. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  5. Predictors of long-term recurrent vascular events after ischemic stroke at young age: the Italian Project on Stroke in Young Adults.

    PubMed

    Pezzini, Alessandro; Grassi, Mario; Lodigiani, Corrado; Patella, Rosalba; Gandolfo, Carlo; Zini, Andrea; Delodovici, Maria Luisa; Paciaroni, Maurizio; Del Sette, Massimo; Toriello, Antonella; Musolino, Rossella; Calabrò, Rocco Salvatore; Bovi, Paolo; Adami, Alessandro; Silvestrelli, Giorgio; Sessa, Maria; Cavallini, Anna; Marcheselli, Simona; Bonifati, Domenico Marco; Checcarelli, Nicoletta; Tancredi, Lucia; Chiti, Alberto; Del Zotto, Elisabetta; Spalloni, Alessandra; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Giacalone, Giacomo; Ferrazzi, Paola; Poli, Loris; Morotti, Andrea; Rasura, Maurizia; Simone, Anna Maria; Gamba, Massimo; Cerrato, Paolo; Micieli, Giuseppe; Melis, Maurizio; Massucco, Davide; De Giuli, Valeria; Iacoviello, Licia; Padovani, Alessandro

    2014-04-22

    Data on long-term risk and predictors of recurrent thrombotic events after ischemic stroke at a young age are limited. We followed 1867 patients with first-ever ischemic stroke who were 18 to 45 years of age (mean age, 36.8±7.1 years; women, 49.0%), as part of the Italian Project on Stroke in Young Adults (IPSYS). Median follow-up was 40 months (25th to 75th percentile, 53). The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. One hundred sixty-three patients had recurrent thrombotic events (average rate, 2.26 per 100 person-years at risk). At 10 years, cumulative risk was 14.7% (95% confidence interval, 12.2%-17.9%) for primary end point, 14.0% (95% confidence interval, 11.4%-17.1%) for brain ischemia, and 0.7% (95% confidence interval, 0.4%-1.3%) for myocardial infarction or other arterial events. Familial history of stroke, migraine with aura, circulating antiphospholipid antibodies, discontinuation of antiplatelet and antihypertensive medications, and any increase of 1 traditional vascular risk factor were independent predictors of the composite end point in multivariable Cox proportional hazards analysis. A point-scoring system for each variable was generated by their β-coefficients, and a predictive score (IPSYS score) was calculated as the sum of the weighted scores. The area under the receiver operating characteristic curve of the 0- to 5-year score was 0.66 (95% confidence interval, 0.61-0.71; mean, 10-fold internally cross-validated area under the receiver operating characteristic curve, 0.65). Among patients with ischemic stroke aged 18 to 45 years, the long-term risk of recurrent thrombotic events is associated with modifiable, age-specific risk factors. The IPSYS score may serve as a simple tool for risk estimation.

  6. Aluminum exposure for one hour decreases vascular reactivity in conductance and resistance arteries in rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schmidt, Patrícia Medeiros; Escobar, Alyne Goulart

    Aims: Aluminum (Al) is an important environmental contaminant; however, there are not enough evidences of Al-induced cardiovascular dysfunction. We investigated the effects of acute exposure to aluminum chloride (AlCl{sub 3}) on blood pressure, vascular reactivity and oxidative stress. Methods and results: Male Wistar rats were divided into two groups: Untreated: vehicle (ultrapure water, ip) and AlCl{sub 3}: single dose of AlCl{sub 3} (100 mg/kg,ip). Concentration-response curves to phenylephrine in the absence and presence of endothelium, the nitric oxide synthase inhibitor L-NAME, the potassium channel blocker tetraethylammonium, and the NADPH oxidase inhibitor apocynin were performed in segments from aortic and mesentericmore » resistance arteries. NO released was assessed in aorta and reactive oxygen species (ROS), malondialdehyde, non-protein thiol levels, antioxidant capacity and enzymatic antioxidant activities were investigated in plasma, aorta and/or mesenteric arteries. After one hour of AlCl{sub 3} exposure serum Al levels attained 147.7 ± 25.0 μg/L. Al treatment: 1) did not affect blood pressure, heart rate and vasodilator responses induced by acetylcholine or sodium nitroprusside; 2) decreased phenylephrine-induced vasoconstrictor responses; 3) increased endothelial modulation of contractile responses, NO release and vascular ROS production from NADPH oxidase; 4) increased plasmatic, aortic and mesenteric malondialdehyde and ROS production, and 5) decreased antioxidant capacity and affected the antioxidant biomarkers non-protein thiol levels, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase enzymatic activities. Conclusion: AlCl{sub 3}-acute exposure reduces vascular reactivity. This effect is associated with increased NO production, probably acting on K{sup +} channels, which seems to occur as a compensatory mechanism against Al-induced oxidative stress. Our results suggest that Al exerts toxic effects to the

  7. Ticagrelor versus clopidogrel in patients with acute coronary syndromes.

    PubMed

    Wallentin, Lars; Becker, Richard C; Budaj, Andrzej; Cannon, Christopher P; Emanuelsson, Håkan; Held, Claes; Horrow, Jay; Husted, Steen; James, Stefan; Katus, Hugo; Mahaffey, Kenneth W; Scirica, Benjamin M; Skene, Allan; Steg, Philippe Gabriel; Storey, Robert F; Harrington, Robert A; Freij, Anneli; Thorsén, Mona

    2009-09-10

    Ticagrelor is an oral, reversible, direct-acting inhibitor of the adenosine diphosphate receptor P2Y12 that has a more rapid onset and more pronounced platelet inhibition than clopidogrel. In this multicenter, double-blind, randomized trial, we compared ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) and clopidogrel (300-to-600-mg loading dose, 75 mg daily thereafter) for the prevention of cardiovascular events in 18,624 patients admitted to the hospital with an acute coronary syndrome, with or without ST-segment elevation. At 12 months, the primary end point--a composite of death from vascular causes, myocardial infarction, or stroke--had occurred in 9.8% of patients receiving ticagrelor as compared with 11.7% of those receiving clopidogrel (hazard ratio, 0.84; 95% confidence interval [CI], 0.77 to 0.92; P<0.001). Predefined hierarchical testing of secondary end points showed significant differences in the rates of other composite end points, as well as myocardial infarction alone (5.8% in the ticagrelor group vs. 6.9% in the clopidogrel group, P=0.005) and death from vascular causes (4.0% vs. 5.1%, P=0.001) but not stroke alone (1.5% vs. 1.3%, P=0.22). The rate of death from any cause was also reduced with ticagrelor (4.5%, vs. 5.9% with clopidogrel; P<0.001). No significant difference in the rates of major bleeding was found between the ticagrelor and clopidogrel groups (11.6% and 11.2%, respectively; P=0.43), but ticagrelor was associated with a higher rate of major bleeding not related to coronary-artery bypass grafting (4.5% vs. 3.8%, P=0.03), including more instances of fatal intracranial bleeding and fewer of fatal bleeding of other types. In patients who have an acute coronary syndrome with or without ST-segment elevation, treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding but with an

  8. FLAIR vascular hyperintensities predict early ischemic recurrence in TIA.

    PubMed

    Nam, Ki-Woong; Kim, Chi Kyung; Kim, Tae Jung; Oh, Kyungmi; Han, Moon-Ku; Ko, Sang-Bae; Yoon, Byung-Woo

    2018-02-27

    To evaluate the relationship between fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) and early ischemic lesion recurrence (follow-up diffusion-weighted imaging [FU-DWI] [+]) in patients with lesion-negative TIA. We recruited consecutive patients with lesion-negative TIA within 24 hours of symptom onset, who underwent follow-up MRI during the acute period. FVH was defined as a focal or serpentine high signal intensity on FLAIR images. Other potential confounders were adjusted to evaluate the relationship between FVH and FU-DWI (+). Furthermore, to compare clinical outcomes between the FU-DWI (+) and FU-DWI (-) groups, we assessed 1-year recurrent ischemic stroke or TIA. Among 392 patients with lesion-negative TIA, 82 patients had FU-DWI (+) on the follow-up MRI. In the multivariate analysis, FVH remained an independent predictor of FU-DWI (+) (adjusted odds ratio [aOR] = 4.77, 95% confidence interval [CI] 2.45-9.29, p < 0.001). The time to initial MRI (aOR = 0.49, 95% CI = 0.33-0.70, p < 0.001) and intracranial atherosclerosis (aOR = 2.07, 95% CI = 1.10-3.92, p = 0.025) were also associated with FU-DWI (+), independent of FVH. In clinical outcomes, the FU-DWI (+) group showed more frequent 1-year recurrent ischemic stroke events than the FU-DWI (-) group (10.7% vs 3.1%, respectively, p = 0.007). FVH is associated with FU-DWI (+) in patients with lesion-negative TIA. As FU-DWI (+) frequently occurs during the acute period and has a subsequent worse outcome after discharge, additional radiologic or clinical markers for it are necessary. © 2018 American Academy of Neurology.

  9. Serial assessment of arterial stiffness by cardio-ankle vascular index for prediction of future cardiovascular events in patients with coronary artery disease.

    PubMed

    Otsuka, Kenichiro; Fukuda, Shota; Shimada, Kenei; Suzuki, Kenji; Nakanishi, Koki; Yoshiyama, Minoru; Yoshikawa, Junichi

    2014-11-01

    Arterial stiffness is a significant predictor of cardiovascular disease (CVD), the risk of which is modified by medications for atherosclerotic risk factors and life-style changes. Cardio-ankle vascular index (CAVI) provides noninvasive, objective information on arterial stiffness, independent of blood pressure. This study aimed to investigate changes in CAVI after management of atherosclerotic risk factors, and the impact of these changes on future CVD outcomes in patients with coronary artery disease (CAD). The study consisted of 211 CAD patients (65 ± 10 years, 118 men) with impaired CAVI. CAVI examination was repeated 6 months later. Impaired CAVI was defined as greater than the mean plus 1 s.d. of the age- and gender-specific normal CAVI values, according to results obtained in 5188 healthy subjects. All patients were followed for > 1 year or until the occurrence of a CVD event. Of the 211 patients, CAVI improved in 106 (50%) patients after 6 months, but remained high in 105 (50%) patients. During follow-up (2.9 ± 1.0 years), CVD events occurred in 28 (13%) patients. Persistently impaired CAVI was an independent predictor of future CVD events (P = 0.01), independent of baseline CAVI. CVD outcomes were worse in patients with persistently impaired CAVI than in those with improved CAVI (P < 0.001). Among patients with a normalized CAVI after treatment (n = 22) only one suffered a CVD event. This study was the first to demonstrate that persistent impairment of arterial stiffness was an independent risk factor of future CVD events. Serial measurements of CAVI provide important prognostic information regarding patients with CAD in clinical practice.

  10. Pulmonary vascular dysfunction in ARDS

    PubMed Central

    2014-01-01

    Acute respiratory distress syndrome (ARDS) is characterised by diffuse alveolar damage and is frequently complicated by pulmonary hypertension (PH). Multiple factors may contribute to the development of PH in this setting. In this review, we report the results of a systematic search of the available peer-reviewed literature for papers that measured indices of pulmonary haemodynamics in patients with ARDS and reported on mortality in the period 1977 to 2010. There were marked differences between studies, with some reporting strong associations between elevated pulmonary arterial pressure or elevated pulmonary vascular resistance and mortality, whereas others found no such association. In order to discuss the potential reasons for these discrepancies, we review the physiological concepts underlying the measurement of pulmonary haemodynamics and highlight key differences between the concepts of resistance in the pulmonary and systemic circulations. We consider the factors that influence pulmonary arterial pressure, both in normal lungs and in the presence of ARDS, including the important effects of mechanical ventilation. Pulmonary arterial pressure, pulmonary vascular resistance and transpulmonary gradient (TPG) depend not alone on the intrinsic properties of the pulmonary vascular bed but are also strongly influenced by cardiac output, airway pressures and lung volumes. The great variability in management strategies within and between studies means that no unified analysis of these papers was possible. Uniquely, Bull et al. (Am J Respir Crit Care Med 182:1123–1128, 2010) have recently reported that elevated pulmonary vascular resistance (PVR) and TPG were independently associated with increased mortality in ARDS, in a large trial with protocol-defined management strategies and using lung-protective ventilation. We then considered the existing literature to determine whether the relationship between PVR/TPG and outcome might be causal. Although we could identify

  11. Hypertrophy of the vasa vasorum: vascular response to the hungry brain.

    PubMed

    Cho, Hyun-Ji; Roh, Hong Gee; Chun, Young Il; Moon, Chang Taek; Chung, Hyun Woo; Kim, Hahn Young

    2012-05-01

    The vasa vasorum is a network of microvessels that supplies nutrients to the vessel wall itself. In pathologic conditions, the vasa vasorum can develop as potential collateral channels. Previous research documents revascularization through hypertrophy of the vasa vasorum after occlusion of the carotid artery. However, the relationship between the cerebral vascular demands and the hypertrophy of the vasa vasorum has not been well delineated by functional studies. A 66-year-old man presented with left hemiparesis, dysarthria, and hemineglect. Magnetic resonance imaging revealed an acute infarction in the vascular territory of the right middle cerebral artery. Transfemoral cerebral angiography revealed occlusion of the right proximal internal carotid artery (ICA). Single-photon emission computed tomography study showed decreased vascular reserve in the right cerebral hemisphere. Right superficial temporal artery-middle cerebral artery bypass surgery was performed in an attempt to improve hemispheric perfusion. Follow-up angiography 1 year later showed revascularization of the distal ICA by the hypertrophied vasa vasorum. Follow-up single-photon emission computed tomography study showed persistent decreased vascular reserve. In cases of ICA occlusion, a 1-year or less hungry period for the cerebral vascular demand may activate potential collateral channels of the vasa vasorum. In addition to the metabolic demand of the occluded vessel wall itself, the vascular demands of the hypoperfused brain may be a trigger factor that leads to hypertrophy of the vasa vasorum as collateral channels.

  12. Pathogenesis of vascular leak in dengue virus infection.

    PubMed

    Malavige, Gathsaurie Neelika; Ogg, Graham S

    2017-07-01

    Endothelial dysfunction leading to vascular leak is the hallmark of severe dengue. Vascular leak typically becomes clinically evident 3-6 days after the onset of illness, which is known as the critical phase. This critical phase follows the period of peak viraemia, and lasts for 24-48 hr and usually shows rapid and complete reversal, suggesting that it is likely to occur as a result of inflammatory mediators, rather than infection of the endothelium. Cytokines such as tumour necrosis factor-α, which are known to be elevated in the critical phase of dengue, are likely to be contributing factors. Dengue NS1, a soluble viral protein, has also been shown to disrupt the endothelial glycocalyx and thus contribute to vascular leak, although there appears to be a discordance between the timing of NS1 antigenaemia and occurrence of vascular leak. In addition, many inflammatory lipid mediators are elevated in acute dengue viral infection such as platelet activating factor (PAF) and leukotrienes. Furthermore, many other inflammatory mediators such as vascular endothelial growth factor and angiopoietin-2 have been shown to be elevated in patients with dengue haemorrhagic fever, exerting their action in part by inducing the activity of phospholipases, which have diverse inflammatory effects including generation of PAF. Platelets have also been shown to significantly contribute to endothelial dysfunction by production of interleukin-1β through activation of the NLRP3 inflammasome and also by inducing production of inflammatory cytokines by monocytes. Drugs that block down-stream immunological mediator pathways such as PAF may also be beneficial in the treatment of severe disease. © 2017 John Wiley & Sons Ltd.

  13. Engineering Pre-vascularized Scaffolds for Bone Regeneration.

    PubMed

    Barabaschi, Giada D G; Manoharan, Vijayan; Li, Qing; Bertassoni, Luiz E

    2015-01-01

    Survival of functional tissue constructs of clinically relevant size depends on the formation of an organized and uniformly distributed network of blood vessels and capillaries. The lack of such vasculature leads to spatio-temporal gradients in oxygen, nutrients and accumulation of waste products inside engineered tissue constructs resulting in negative biological events at the core of the scaffold. Unavailability of a well-defined vasculature also results in ineffective integration of scaffolds to the host vasculature upon implantation. Arguably, one of the greatest challenges in engineering clinically relevant bone substitutes, therefore, has been the development of vascularized bone scaffolds. Various approaches ranging from peptide and growth factor functionalized biomaterials to hyper-porous scaffolds have been proposed to address this problem with reasonable success. An emerging alternative to address this challenge has been the fabrication of pre-vascularized scaffolds by taking advantage of biomanufacturing techniques, such as soft- and photo-lithography or 3D bioprinting, and cell-based approaches, where functional capillaries are engineered in cell-laden scaffolds prior to implantation. These strategies seek to engineer pre-vascularized tissues in vitro, allowing for improved anastomosis with the host vasculature upon implantation, while also improving cell viability and tissue development in vitro. This book chapter provides an overview of recent methods to engineer pre-vascularized scaffolds for bone regeneration. We first review the development of functional blood capillaries in bony structures and discuss controlled delivery of growth factors, co-culture systems, and on-chip studies to engineer vascularized cell-laden biomaterials. Lastly, we review recent studies using microfabrication techniques and 3D printing to engineer pre-vascularized scaffolds for bone tissue engineering.

  14. The pathology and pathophysiology of vascular dementia.

    PubMed

    Kalaria, Raj N

    2017-12-19

    Vascular dementia (VaD) is widely recognised as the second most common type of dementia. Consensus and accurate diagnosis of clinically suspected VaD relies on wide-ranging clinical, neuropsychological and neuroimaging measures in life but more importantly pathological confirmation. Factors defining subtypes of VaD include the nature and extent of vascular pathologies, degree of involvement of extra and intracranial vessels and the anatomical location of tissue changes as well as time after the initial vascular event. Atherosclerotic and cardioembolic diseases combined appear the most common subtypes of vascular brain injury. In recent years, cerebral small vessel disease (SVD) has gained prominence worldwide as an important substrate of cognitive impairment. SVD is characterised by arteriolosclerosis, lacunar infarcts and cortical and subcortical microinfarcts and diffuse white matter changes, which involve myelin loss and axonal abnormalities. Global brain atrophy and focal degeneration of the cerebrum including medial temporal lobe atrophy are also features of VaD similar to Alzheimer's disease. Hereditary arteriopathies have provided insights into the mechanisms of dementia particularly how arteriolosclerosis, a major contributor of SVD promotes cognitive impairment. Recently developed and validated neuropathology guidelines indicated that the best predictors of vascular cognitive impairment were small or lacunar infarcts, microinfarcts, perivascular space dilation, myelin loss, arteriolosclerosis and leptomeningeal cerebral amyloid angiopathy. While these substrates do not suggest high specificity, VaD is likely defined by key neuronal and dendro-synaptic changes resulting in executive dysfunction and related cognitive deficits. Greater understanding of the molecular pathology is needed to clearly define microvascular disease and vascular substrates of dementia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Non-neural BOLD variability in block and event-related paradigms.

    PubMed

    Kannurpatti, Sridhar S; Motes, Michael A; Rypma, Bart; Biswal, Bharat B

    2011-01-01

    Block and event-related stimulus designs are typically used in fMRI studies depending on the importance of detection power or estimation efficiency. The extent of vascular contribution to variability in block and event-related fMRI-BOLD response is not known. With scaling, the extent of vascular variability in the fMRI-BOLD response during block and event-related design tasks was investigated. Blood oxygen level-dependent (BOLD) contrast data from healthy volunteers performing a block design motor task and an event-related memory task requiring performance of a motor response were analyzed from the regions of interest (ROIs) surrounding the primary and supplementary motor cortices. Average BOLD signal change was significantly larger during the block design compared to the event-related design. In each subject, BOLD signal change across voxels in the ROIs had higher variation during the block design task compared to the event-related design task. Scaling using the resting state fluctuation of amplitude (RSFA) and breath-hold (BH), which minimizes BOLD variation due to vascular origins, reduced the within-subject BOLD variability in every subject during both tasks but significantly reduced BOLD variability across subjects only during the block design task. The strong non-neural source of intra- and intersubject variability of BOLD response during the block design compared to event-related task indicates that study designs optimizing for statistical power through enhancement of the BOLD contrast (for, e.g., block design) can be affected by enhancement of non-neural sources of BOLD variability. Copyright © 2011. Published by Elsevier Inc.

  16. Emerging diagnostic and therapeutic molecular imaging applications in vascular disease

    PubMed Central

    Eraso, Luis H; Reilly, Muredach P; Sehgal, Chandra; Mohler, Emile R

    2013-01-01

    Assessment of vascular disease has evolved from mere indirect and direct measurements of luminal stenosis to sophisticated imaging methods to depict millimeter structural changes of the vasculature. In the near future, the emergence of multimodal molecular imaging strategies may enable robust therapeutic and diagnostic (‘theragnostic’) approaches to vascular diseases that comprehensively consider structural, functional, biological and genomic characteristics of the disease in individualized risk assessment, early diagnosis and delivery of targeted interventions. This review presents a summary of recent preclinical and clinical developments in molecular imaging and theragnostic applications covering diverse atherosclerosis events such as endothelial activation, macrophage infammatory activity, plaque neovascularization and arterial thrombosis. The main focus is on molecular targets designed for imaging platforms commonly used in clinical medicine including magnetic resonance, computed tomography and positron emission tomography. A special emphasis is given to vascular ultrasound applications, considering the important role this imaging platform plays in the clinical and research practice of the vascular medicine specialty. PMID:21310769

  17. Acute tamponade alters subendo- and subepicardial pressure-flow relations differently during vasodilation.

    PubMed

    Kingma, J G; Martin, J; Rouleau, J R

    1994-07-01

    Instantaneous diastolic left coronary artery pressure-flow relations (PFR) shift during acute tamponade as pressure surrounding the heart increases. Coronary pressure at zero flow (Pf = 0) on the linear portion of the PFR is the weighted mean of the different myocardial waterfall pressures, the distribution of which varies across the left ventricular wall during diastole. However, instantaneous PFR measured in large epicardial coronary arteries cannot be used to estimate Pf = 0 in the different myocardial tissue layers. During coronary vasodilatation in a capacitance-free model, myocardial PFR differs from subendocardium to subepicardium. Therefore, we studied the effects of acute tamponade during maximal pharmacology induced coronary vasodilatation on myocardial PFR in in situ anesthetized dogs. Tamponade reduced cardiac output, aortic pressure, and coronary blood flow. Results demonstrate that different mechanisms influence distribution of myocardial blood flow during tamponade. Subepicardial vascular resistance is unchanged and the extrapolated Pf = 0 is increased, thereby shifting PFR to a higher intercept on the pressure axis. Subendocardial vascular resistance is increased while the extrapolated Pf = 0 remains unchanged. Results indicate that in the setting of acute tamponade with coronary vasodilatation different mechanisms regulate the distribution of myocardial blood flow: in the subepicardium only outflow pressure increases, whereas in the subendocardium only vascular resistance increases.

  18. Critical role of sphingosine-1-phosphate receptor 2 (S1PR2) in acute vascular inflammation.

    PubMed

    Zhang, Guoqi; Yang, Li; Kim, Gab Seok; Ryan, Kieran; Lu, Shulin; O'Donnell, Rebekah K; Spokes, Katherine; Shapiro, Nathan; Aird, William C; Kluk, Michael J; Yano, Kiichiro; Sanchez, Teresa

    2013-07-18

    The endothelium, as the interface between blood and all tissues, plays a critical role in inflammation. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid, highly abundant in plasma, that potently regulates endothelial responses through interaction with its receptors (S1PRs). Here, we studied the role of S1PR2 in the regulation of the proadhesion and proinflammatory phenotype of the endothelium. By using genetic approaches and a S1PR2-specific antagonist (JTE013), we found that S1PR2 plays a key role in the permeability and inflammatory responses of the vascular endothelium during endotoxemia. Experiments with bone marrow chimeras (S1pr2(+/+) → S1pr2(+/+), S1pr2(+/+) → S1pr2(-/-), and S1pr2(-/-) → S1pr2(+/+)) indicate the critical role of S1PR2 in the stromal compartment, in the regulation of vascular permeability and vascular inflammation. In vitro, JTE013 potently inhibited tumor necrosis factor α-induced endothelial inflammation. Finally, we provide detailed mechanisms on the downstream signaling of S1PR2 in vascular inflammation that include the activation of the stress-activated protein kinase pathway that, together with the Rho-kinase nuclear factor kappa B pathway (NF-kB), are required for S1PR2-mediated endothelial inflammatory responses. Taken together, our data indicate that S1PR2 is a key regulator of the proinflammatory phenotype of the endothelium and identify S1PR2 as a novel therapeutic target for vascular disorders.

  19. CT and MRI imaging at the acute phase of inaugural non-traumatic hepatic haemorrhages.

    PubMed

    Boulouis, G; Marmin, C; Lemaire, S; Boury, S; Sergent, G; Mordon, S; Ernst, O

    2013-03-01

    Although rare, non-traumatic hepatic haemorrhage is a known complication of liver tumors. In cases where the haemorrhage is the first clinical event, diagnostic work-up is critical. This retrospective study was conducted between July 2001 and March 2011. Acute phase CT-scan and MRI imaging in patients diagnosed with non-traumatic liver hematomas were interpreted with particular attention to the radio-semiotic characteristics of hematomas and liver lesions. Those findings were then confronted to the patients' final diagnoses. Twelve patients were included (mean age of 42 years). In seven of them a suspect liver lesion was discovered in the acute CT-Scan or MRI imaging. All lesions were strongly hyper vascular.The haemorrhage revealed hepatocarcinoma in four patients, liver adenoma in two and focal nodular hyperplasia in an other. It is important in spontaneous liver haemorrhage to consider the high probability of hepatocarcinoma or potentially malignant lesions even when the patient has no known hepatic disorders, and especially in young patients. The results of this study show that imaging is a key issue at the acute phase of inaugural non-traumatic hepatic haemorrhages and requires a simple but complete triphasic injected protocol. Copyright © 2012 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

  20. [Aspects of vascular physiology in clinical and vascular surgical practice: basic principles of vascular mechanics].

    PubMed

    Nocke, H; Meyer, F; Lessmann, V

    2014-10-01

    To be able to evaluate properly a vascular problem, basic concepts of vascular physiology need to be considered, as they have been taught in physiology for a long time. This article deals with selected definitions and laws of passive vascular mechanics, subdivided into parameters of vascular filling and parameters of vascular flow. PARAMETERS OF VASCULAR FILLING: During vascular filling the transmural pressure distends the vascular wall until it is balanced by the wall tension. The extent of this distension up to the point of balance depends on the elasticity of the wall. Transmural pressure, wall tension and elasticity are defined, and their respective importance is described by clinical examples, e.g. aneurysm and varix. PARAMETERS OF VASCULAR FLOW: The vascular flow can be divided into stationary and pulsating components. Both components are relevant for the bloodstream. Since the blood flow is directed in the circuit, it can be understood in first approximation as stationary ("direct current").The direct current model uses only the average values of the pulsating variables. The great advantage of the direct current model is that it can be described with simple laws, which are not valid without reservation, but often allow a first theoretical approach to a vascular problem: Ohm's law, driving pressure, flow resistance, Hagen-Poiseuille law, wall shear stress, law of continuity, Bernoulli's equation and Reynold's number are described and associated with clinical examples.The heart is a pressure-suction pump and produces a pulsating flow, the pulse. The pulse runs with pulse wave velocity, which is much larger than the blood flow velocity, through the arterial vascular system. During propagation, the pulse has to overcome the wave resistance (impedance). Wherever the wave resistance changes, e.g., at vascular bifurcations and in the periphery, it comes to reflections. The incident (forward) and reflected (backward) waves are superimposed to yield the resulting

  1. Acute adverse events associated with the administration of Crotalidae polyvalent immune Fab antivenom within the North American Snakebite Registry.

    PubMed

    Kleinschmidt, Kurt; Ruha, Anne-Michelle; Campleman, Sharan; Brent, Jeffrey; Wax, Paul

    2018-04-24

    Crotalidae Polyvalent Immune Fab (Fab Antivenom) is the primary Viperid antivenom used in the United States since 2000. Adverse event data associated with its use are limited. The purpose of this study is to describe the prevalence of acute adverse events associated with the use of Fab antivenom. The American College of Medical Toxicology's Toxicology Investigators Consortium maintains a prospective case registry of poisoned and envenomated patients managed by medical toxicologists at the bedside. This registry includes the North American Snakebite sub-registry. We performed a review of 438 cases entered into the Snakebite sub-registry. A total of 373 (85.2%) received at least one vial of Fab Antivenom. Forty percent were children. Adverse events occurred in 10 patients (2.7%) of whom six were adults. Rash was the most common adverse event. More severe adverse events (hypotension, bronchospasm, and/or angioedema) occurred in four (1.1%) patients. Prophylaxis was administered prior to Fab antivenom in 4.0%. Eight patients received various treatments for their adverse events. Neither the initial number of Fab antivenom vials, atopic history, nor prior envenomation correlated with the prevalence of adverse events. This prevalence of adverse events was lower than in previous studies and in a meta-analysis of 11 studies. The types of adverse events and treatments used are consistent with those in previous reports. There were no prior reports of prophylaxis use with which to compare. The prevalence of Fab antivenom adverse events in the North American Snakebite Registry was 2.7%.

  2. The making of indigenous vascular prosthesis

    PubMed Central

    Unnikrishnan, Madathipat; Viswanathan, Sidharth; Balasubramaniam, K.; Muraleedharan, C.V.; Lal, Arthur Vijayan; Mohanan, P.V.; Mohanty, Meera; Kapilamoorthy, Tirur Raman

    2016-01-01

    Background & objectives: Vascular illnesses are on the rise in India, due to increase in lifestyle diseases and demographic transition, requiring intervention to save life, organ or limbs using vascular prosthesis. The aim of this study was to develop indigenous large diameter vascular graft for treatment of patients with vascular pathologies. Methods: The South India Textile Research Association, at Coimbatore, Tamil Nadu, India, developed seamless woven polyester (Polyethylene terephthalate) graft at its research wing. Further characterization and testing followed by clinical trials were conducted at Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India. Fifteen in vivo experiments were carried out in 1992-1994 in pigs as animal model. Controlled (phase I) clinical trial in ten patients was performed along with control graft. Thereafter, phase II trial involved 22 patients who underwent multi-centre clinical trial in four centres across India. Results: Laboratory testing showed that polyester graft was non-toxic, non-leeching and non-haemolytic with preserved long-term quality, further confirming in pigs by implanting in thoracic aorta, comparable to control Dacron grafts. Perigraft incorporation and smooth neointima formation which are prime features of excellent healing characteristics, were noted at explantation at planned intervals. Subsequently in the phase I and II clinical trials, all patients had excellent recovery without mortality or device-related adverse events. Patients receiving the test graft were followed up for 10 and 5 years, respectively. Serial clinical, duplex scans and CT angiograms performed periodically confirmed excellent graft performance. Interpretation & conclusions: Indigenously developed Chitra vascular graft was comparable to commercially available Dacron graft, ready for clinical use at affordable cost to patients as against costly imported grafts. PMID:27748302

  3. Combining clinical and thallium data optimizes preoperative assessment of cardiac risk before major vascular surgery

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Eagle, K.A.; Coley, C.M.; Newell, J.B.

    1989-06-01

    STUDY OBJECTIVE: To determine whether clinical markers and preoperative dipyridamole-thallium imaging are both useful in predicting ischemic events after vascular surgery. Two hundred fifty-four consecutive patients were referred to a nuclear cardiology laboratory before surgery. Forty-four patients had surgery cancelled or postponed after clinical evaluation and dipyridamole-thallium imaging. Surgery was not confirmed for ten. Two hundred patients receiving prompt vascular surgery were the study group. Thirty patients (15%) had early postoperative cardiac ischemic events, with cardiac death in 6 (3%) and nonfatal myocardial infarction in 9 (4.5%). Logistic regression identified five clinical predictors (Q waves, history of ventricular ectopic activity,more » diabetes, advanced age, angina) and two dipyridamole-thallium predictors of postoperative events. Of patients with none of the clinical variables (n = 64), only 2 (3.1%; 95% CI, 0% to 8%) had ischemic events with no cardiac deaths. Ten of twenty (50%; 95% CI, 29% to 71%) patients with three or more clinical markers had events. Eighteen of one hundred sixteen (15.5%; 95% CI, 7% to 21%) patients with either 1 or 2 clinical predictors had events. Within this group, 2 of 62 (3.2%; 95% CI, 0% to 8%) patients without thallium redistribution had events compared with 16 events in 54 patients (29.6%; 95% CI, 16% to 44%) with thallium redistribution. The multivariate model using both clinical and thallium variables showed significantly higher specificity at equivalent sensitivity levels than models using either clinical or thallium variables alone. Preoperative dipyridamole-thallium imaging appears most useful to stratify vascular patients determined to be at intermediate risk by clinical evaluation.« less

  4. Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs.

    PubMed

    Elomaa, Laura; Yang, Yunzhi Peter

    2017-10-01

    There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

  5. Acute peri-operative beta blockade in intermediate-risk patients.

    PubMed

    Biccard, B M; Sear, J W; Foëx, P

    2006-10-01

    Peri-operative beta-blockade has been shown to reduce the incidence of postoperative cardio- vascular complications including cardiac death in high-risk non-cardiac surgical patients. However, the recent analysis by Lindenauer et al. suggests that it is inappropriate to administer beta-blockers blindly to all surgical patients. In an attempt to determine the appropriateness of peri-operative beta-blocker administration across patients with a spectrum of cardiovascular risks, we have examined studies of intermediate-risk patient groups (that is those undergoing intermediate risk surgery or those with a Lee Revised Cardiac Risk Score of < or =2). We analysed data from randomised prospective studies of the effects of acute peri-operative beta-blockade on the incidence of peri-operative myocardial ischaemia. By examining the demographics and surgical interventions in these patients, we have compared these studies with other studies of peri-operative silent myocardial ischaemia representing patients of similar risk. We thus estimated the expected long-term postoperative cardiovascular complication rate associated with myocardial ischaemia in these patients in terms of number needed to treat for ischaemia prevention and for prevention of major cardiovascular complications. Prevention of peri-operative myocardial ischaemia with acute beta-blockade in non-cardiac surgical patients with 1-2 RCRI clinical risk factors can be achieved with a number needed to treat of 10. It is not associated with a significant increase in drug associated side-effects. However, acute beta-blockade shows no real benefit in the prevention of major cardiovascular complications in intermediate risk non-vascular surgical patients with a number-needed-to-treat of 833. Vascular surgical patients undergoing intermediate-risk surgery may benefit from the protective effects of acute peri-operative beta-blockade, however, with a number-needed-to-treat of 68 it would require a randomised clinical trial of

  6. Effects of acute inhalation of aerosols generated during resistance spot welding with mild-steel on pulmonary, vascular and immune responses in rats.

    PubMed

    Zeidler-Erdely, Patti C; Meighan, Terence G; Erdely, Aaron; Fedan, Jeffrey S; Thompson, Janet A; Bilgesu, Suzan; Waugh, Stacey; Anderson, Stacey; Marshall, Nikki B; Afshari, Aliakbar; McKinney, Walter; Frazer, David G; Antonini, James M

    2014-10-01

    Spot welding is used in the automotive and aircraft industries, where high-speed, repetitive welding is needed to join thin sections of metal. Epoxy adhesives are applied as sealers to the metal seams. Pulmonary function abnormalities and airway irritation have been reported in spot welders, but no animal toxicology studies exist. Therefore, the goal of this study was to investigate vascular, immune and lung toxicity measures after exposure to these metal fumes in an animal model. Male Sprague-Dawley rats were exposed by inhalation to 25 mg/m³ to either mild-steel spot welding aerosols with sparking (high metal, HM) or without sparking (low metal, LM) for 4 h/d for 3, 8 and 13 d. Shams were exposed to filtered air. Bronchoalveolar lavage (BAL), lung gene expression and ex vivo BAL cell challenge were performed to assess lung toxicity. Lung resistance (R(L)) was evaluated before and after challenge with inhaled methacholine (MCh). Functional assessment of the vascular endothelium in isolated rat tail arteries and leukocyte differentiation in the spleen and lymph nodes via flow cytometry was also done. Immediately after exposure, baseline R(L) was significantly elevated in the LM spot welding aerosols, but returned to control level by 24 h postexposure. Airway reactivity to MCh was unaffected. Lung inflammation and cytotoxicity were mild and transient. Lung epithelial permeability was significantly increased after 3 and 8 d, but not after 13 d of exposure to the HM aerosol. HM aerosols also caused vascular endothelial dysfunction and increased CD4+, CD8+ and B cells in the spleen. Only LM aerosols caused increased IL-6 and MCP-1 levels compared with sham after ex vivo LPS stimulation in BAL macrophages. Acute inhalation of mild-steel spot welding fumes at occupationally relevant concentrations may act as an irritant as evidenced by the increased R(L) and result in endothelial dysfunction, but otherwise had minor effects on the lung.

  7. Effects of acute inhalation of aerosols generated during resistance spot welding with mild-steel on pulmonary, vascular and immune responses in rats

    PubMed Central

    Zeidler-Erdely, Patti C.; Meighan, Terence G.; Erdely, Aaron; Fedan, Jeffrey S.; Thompson, Janet A.; Bilgesu, Suzan; Waugh, Stacey; Anderson, Stacey; Marshall, Nikki B.; Afshari, Aliakbar; McKinney, Walter; Frazer, David G.; Antonini, James M.

    2015-01-01

    Spot welding is used in the automotive and aircraft industries, where high-speed, repetitive welding is needed to join thin sections of metal. Epoxy adhesives are applied as sealers to the metal seams. Pulmonary function abnormalities and airway irritation have been reported in spot welders, but no animal toxicology studies exist. Therefore, the goal of this study was to investigate vascular, immune and lung toxicity measures after exposure to these metal fumes in an animal model. Male Sprague-Dawley rats were exposed by inhalation to 25 mg/m3 to either mild-steel spot welding aerosols with sparking (high metal, HM) or without sparking (low metal, LM) for 4 h/d for 3, 8 and 13 d. Shams were exposed to filtered air. Bronchoalveolar lavage (BAL), lung gene expression and ex vivo BAL cell challenge were performed to assess lung toxicity. Lung resistance (RL) was evaluated before and after challenge with inhaled methacholine (MCh). Functional assessment of the vascular endothelium in isolated rat tail arteries and leukocyte differentiation in the spleen and lymph nodes via flow cytometry was also done. Immediately after exposure, baseline RL was significantly elevated in the LM spot welding aerosols, but returned to control level by 24 h postexposure. Airway reactivity to MCh was unaffected. Lung inflammation and cytotoxicity were mild and transient. Lung epithelial permeability was significantly increased after 3 and 8 d, but not after 13 d of exposure to the HM aerosol. HM aerosols also caused vascular endothelial dysfunction and increased CD4+, CD8+ and B cells in the spleen. Only LM aerosols caused increased IL-6 and MCP-1 levels compared with sham after ex vivo LPS stimulation in BAL macrophages. Acute inhalation of mild-steel spot welding fumes at occupationally relevant concentrations may act as an irritant as evidenced by the increased RL and result in endothelial dysfunction, but otherwise had minor effects on the lung. PMID:25140454

  8. Auditory event-related potentials in subcortical vascular cognitive impairment and in Alzheimer's disease.

    PubMed

    Muscoso, E G; Costanzo, E; Daniele, O; Maugeri, D; Natale, E; Caravaglios, G

    2006-11-01

    Few studies exist on ERPs and patients with subcortical vascular cognitive impairment (SVCI). This latter is a quite homogeneous subtype of vascular dementia whose cognitive profile is quite different from that of Alzheimer disease (AD). The present study aims at comparing the ERPs profile both in patients with SVCI and in patients with AD. ERPs and psychometric tests were collected from 39 healthy elderly controls, 51 patients with SVCI and 43 patients with AD. Subjects mentally count high pitched target tones that were randomly intermixed with low pitched frequent tones. We measured ERPs latencies (N1, P2, N2 and P3), and interpeak latencies (N1-P3, N1-P2, N1-N2). Grand averaged potentials in SVCI showed a significant increase of P3 latency. AD patients showed a prolongation of N1, P2, N2, P3 latencies. As far as interpeak latencies are concerned, SVCI patients showed a significant prolongation of N1-P3, AD patients had a significant increase of N1-N2, and N1-P3 intervals. When all patients were considered as a single group, correlation of neuropsychological tests scores showed a significant negative relationship between P300 latency and, respectively, Mini Mental Status Examination, auditive and visual span forward. In both groups, ERPs latency sensitivity, was low, whilst specificity values were quite high. Our finding suggest that these two dementing diseases have different electrophysiologic features that may be related to their specific underlying pathogenetic mechanism; in particular, we hypothesise that, differently from AD, P300 latency prolongation characterizes the early stage of SVCI. So, this ERPs approach could be helpful to detect early alterations of the attentional/working-memory functions in patients with subcortical ischaemic vascular disease.

  9. Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system.

    PubMed

    Sakaeda, Toshiyuki; Kadoyama, Kaori; Okuno, Yasushi

    2011-01-01

    Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and to attempt to determine the rank-order of the association. After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events.

  10. Contemporary Strategies in the Management of Civilian Abdominal Vascular Trauma

    PubMed Central

    Karaolanis, Georgios; Moris, Dimitrios; McCoy, C. Cameron; Tsilimigras, Diamantis I.; Georgopoulos, Sotirios; Bakoyiannis, Chris

    2018-01-01

    The evaluation and management of patients with abdominal vascular trauma or injury requires immediate and effective decision-making in these unfavorable circumstances. The majority of these patients arrive at trauma centers in profound shock, secondary to massive blood loss, which is often unrelenting. Moreover, ischemia, compartment syndrome, thrombosis, and embolization may also be life threatening and require immediate intervention. To minimize the risk of these potentially lethal complications, early understanding of the disease process and emergent therapeutic intervention are necessary. In the literature, the management of acute traumatic vascular injuries is restricted to traditional open surgical techniques. However, in penetrating injuries surgeons often face a potentially contaminated field, which renders the placement of prosthetic grafts inappropriate. Currently, however, there are sparse data on the management of vascular trauma with endovascular techniques. The role of endovascular technique in penetrating abdominal vascular trauma, which is almost always associated with severe active bleeding, is limited. It is worth mentioning that hybrid operating rooms with angiographic radiology capabilities offer more opportunities for the management of this kind of injuries by either temporary control of the devastating bleeding using endovascular balloon tamponade or with embolization and stenting. On the other hand, blunt abdominal injuries are less dangerous and they could be treated at most times by endovascular means. Since surgeons continue to encounter abdominal vascular trauma, open and endovascular techniques will evolve constantly giving us encouraging messages for the near future. PMID:29516005

  11. εPKC confers acute tolerance to cerebral ischemic reperfusion injury

    PubMed Central

    Bright, Rachel; Sun, Guo-Hua; Yenari, Midori A.; Steinberg, Gary K.; Mochly-Rosen, Daria

    2008-01-01

    In response to mild ischemic stress, the brain elicits endogenous survival mechanisms to protect cells against a subsequent lethal ischemic stress, referred to as ischemic tolerance. The molecular signals that mediate this protection are thought to involve the expression and activation of multiple kinases, including protein kinase C (PKC). Here we demonstrate that εPKC mediates cerebral ischemic tolerance in vivo. Systemic delivery of ψεRACK, an εPKC-selective peptide activator, confers neuroprotection against a subsequent cerebral ischemic event when delivered immediately prior to stroke. In addition, activation of εPKC by ψεRACK treatment decreases vascular tone in vivo, as demonstrated by a reduction in microvascular cerebral blood flow. Here we demonstrate the role of acute and transient εPKC in early cerebral tolerance in vivo and suggest that extra-parenchymal mechanisms, such as vasoconstriction, may contribute to the conferred protection. PMID:18586397

  12. Pathophysiological Approaches of Acute Respiratory Distress syndrome: Novel Bases for Study of Lung Injury

    PubMed Central

    Castillo, R.L; Carrasco Loza, R; Romero-Dapueto, C

    2015-01-01

    Experimental approaches have been implemented to research the lung damage related-mechanism. These models show in animals pathophysiological events for acute respiratory distress syndrome (ARDS), such as neutrophil activation, reactive oxygen species burst, pulmonary vascular hypertension, exudative edema, and other events associated with organ dysfunction. Moreover, these approaches have not reproduced the clinical features of lung damage. Lung inflammation is a relevant event in the develop of ARDS as component of the host immune response to various stimuli, such as cytokines, antigens and endotoxins. In patients surviving at the local inflammatory states, transition from injury to resolution is an active mechanism regulated by the immuno-inflammatory signaling pathways. Indeed, inflammatory process is regulated by the dynamics of cell populations that migrate to the lung, such as neutrophils and on the other hand, the role of the modulation of transcription factors and reactive oxygen species (ROS) sources, such as nuclear factor kappaB and NADPH oxidase. These experimental animal models reproduce key components of the injury and resolution phases of human ALI/ARDS and provide a methodology to explore mechanisms and potential new therapies. PMID:26312099

  13. A microengineered model of RBC transfusion-induced pulmonary vascular injury.

    PubMed

    Seo, Jeongyun; Conegliano, David; Farrell, Megan; Cho, Minseon; Ding, Xueting; Seykora, Thomas; Qing, Danielle; Mangalmurti, Nilam S; Huh, Dongeun

    2017-06-13

    Red blood cell (RBC) transfusion poses significant risks to critically ill patients by increasing their susceptibility to acute respiratory distress syndrome. While the underlying mechanisms of this life-threatening syndrome remain elusive, studies suggest that RBC-induced microvascular injury in the distal lung plays a central role in the development of lung injury following blood transfusion. Here we present a novel microengineering strategy to model and investigate this key disease process. Specifically, we created a microdevice for culturing primary human lung endothelial cells under physiological flow conditions to recapitulate the morphology and hemodynamic environment of the pulmonary microvascular endothelium in vivo. Perfusion of the microengineered vessel with human RBCs resulted in abnormal cytoskeletal rearrangement and release of intracellular molecules associated with regulated necrotic cell death, replicating the characteristics of acute endothelial injury in transfused lungs in vivo. Our data also revealed the significant effect of hemodynamic shear stress on RBC-induced microvascular injury. Furthermore, we integrated the microfluidic endothelium with a computer-controlled mechanical stretching system to show that breathing-induced physiological deformation of the pulmonary microvasculature may exacerbate vascular injury during RBC transfusion. Our biomimetic microsystem provides an enabling platform to mechanistically study transfusion-associated pulmonary vascular complications in susceptible patient populations.

  14. Secular trends in acute dialysis after elective major surgery — 1995 to 2009

    PubMed Central

    Siddiqui, Nausheen F.; Coca, Steven G.; Devereaux, Philip J.; Jain, Arsh K.; Li, Lihua; Luo, Jin; Parikh, Chirag R.; Paterson, Michael; Philbrook, Heather Thiessen; Wald, Ron; Walsh, Michael; Whitlock, Richard; Garg, Amit X.

    2012-01-01

    Background: Acute kidney injury is a serious complication of elective major surgery. Acute dialysis is used to support life in the most severe cases. We examined whether rates and outcomes of acute dialysis after elective major surgery have changed over time. Methods: We used data from Ontario’s universal health care databases to study all consecutive patients who had elective major surgery at 118 hospitals between 1995 and 2009. Our primary outcomes were acute dialysis within 14 days of surgery, death within 90 days of surgery and chronic dialysis for patients who did not recover kidney function. Results: A total of 552 672 patients underwent elective major surgery during the study period, 2231 of whom received acute dialysis. The incidence of acute dialysis increased steadily from 0.2% in 1995 (95% confidence interval [CI] 0.15–0.2) to 0.6% in 2009 (95% CI 0.6–0.7). This increase was primarily in cardiac and vascular surgeries. Among patients who received acute dialysis, 937 died within 90 days of surgery (42.0%, 95% CI 40.0–44.1), with no change in 90-day survival over time. Among the 1294 patients who received acute dialysis and survived beyond 90 days, 352 required chronic dialysis (27.2%, 95% CI 24.8–29.7), with no change over time. Interpretation: The use of acute dialysis after cardiac and vascular surgery has increased substantially since 1995. Studies focusing on interventions to better prevent and treat perioperative acute kidney injury are needed. PMID:22733671

  15. Nestin upregulation characterizes vascular remodeling secondary to hypertension in the rat.

    PubMed

    Tardif, Kim; Hertig, Vanessa; Duquette, Natacha; Villeneuve, Louis; El-Hamamsy, Ismail; Tanguay, Jean-François; Calderone, Angelino

    2015-05-15

    Proliferation and hypertrophy of vascular smooth muscle cells represent hallmark features of vessel remodeling secondary to hypertension. The intermediate filament protein nestin was recently identified in vascular smooth muscle cells and in other cell types directly participated in proliferation. The present study tested the hypothesis that vessel remodeling secondary to hypertension was characterized by nestin upregulation in vascular smooth muscle cells. Two weeks after suprarenal abdominal aorta constriction of adult male Sprague-Dawley rats, elevated mean arterial pressure increased the media area and thickness of the carotid artery and aorta and concomitantly upregulated nestin protein levels. In the normal adult rat carotid artery, nestin immunoreactivity was observed in a subpopulation of vascular smooth muscle cells, and the density significantly increased following suprarenal abdominal aorta constriction. Filamentous nestin was detected in cultured rat carotid artery- and aorta-derived vascular smooth muscle cells and an analogous paradigm observed in human aorta-derived vascular smooth muscle cells. ANG II and EGF treatment of vascular smooth muscle cells stimulated DNA and protein synthesis and increased nestin protein levels. Lentiviral short-hairpin RNA-mediated nestin depletion of carotid artery-derived vascular smooth muscle cells inhibited peptide growth factor-stimulated DNA synthesis, whereas protein synthesis remained intact. These data have demonstrated that vessel remodeling secondary to hypertension was characterized in part by nestin upregulation in vascular smooth muscle cells. The selective role of nestin in peptide growth factor-stimulated DNA synthesis has revealed that the proliferative and hypertrophic responses of vascular smooth muscle cells were mediated by divergent signaling events. Copyright © 2015 the American Physiological Society.

  16. Myocardial Bridge and Acute Plaque Rupture

    PubMed Central

    Perl, Leor; Daniels, David; Schwartz, Jonathan; Tanaka, Shige; Yeung, Alan; Tremmel, Jennifer A.; Schnittger, Ingela

    2016-01-01

    A myocardial bridge (MB) is a common anatomic variant, most frequently located in the left anterior descending coronary artery, where a portion of the coronary artery is covered by myocardium. Importantly, MBs are known to result in a proximal atherosclerotic lesion. It has recently been postulated that these lesions predispose patients to acute coronary events, even in cases of otherwise low-risk patients. One such mechanism may involve acute plaque rupture. In this article, we report 2 cases of patients with MBs who presented with acute coronary syndromes despite having low cardiovascular risk. Their presentation was life-risking and both were treated urgently and studied with coronary angiographies and intravascular ultrasound. This latter modality confirmed a rupture of an atherosclerotic plaque proximal to the MB as a likely cause of the acute events. These cases, of unexplained acute coronary syndrome in low-risk patients, raise the question of alternative processes leading to the event and the role MB play as an underlying cause of ruptured plaques. In some cases, an active investigation for this entity may be warranted, due to the prognostic implications of the different therapeutic modalities, should an MB be discovered. PMID:28251167

  17. Myocardial Bridge and Acute Plaque Rupture.

    PubMed

    Perl, Leor; Daniels, David; Schwartz, Jonathan; Tanaka, Shige; Yeung, Alan; Tremmel, Jennifer A; Schnittger, Ingela

    2016-01-01

    A myocardial bridge (MB) is a common anatomic variant, most frequently located in the left anterior descending coronary artery, where a portion of the coronary artery is covered by myocardium. Importantly, MBs are known to result in a proximal atherosclerotic lesion. It has recently been postulated that these lesions predispose patients to acute coronary events, even in cases of otherwise low-risk patients. One such mechanism may involve acute plaque rupture. In this article, we report 2 cases of patients with MBs who presented with acute coronary syndromes despite having low cardiovascular risk. Their presentation was life-risking and both were treated urgently and studied with coronary angiographies and intravascular ultrasound. This latter modality confirmed a rupture of an atherosclerotic plaque proximal to the MB as a likely cause of the acute events. These cases, of unexplained acute coronary syndrome in low-risk patients, raise the question of alternative processes leading to the event and the role MB play as an underlying cause of ruptured plaques. In some cases, an active investigation for this entity may be warranted, due to the prognostic implications of the different therapeutic modalities, should an MB be discovered.

  18. [Experience of Regional Vascular Centre in assisting patients with severe cerebrovascular accidents in Novosibirsk].

    PubMed

    Doronin, B M; Marushak, A A; Popova, T F; Gribacheva, I A; Petrova, E V

    2016-01-01

    The analysis of the work of the neurological department of the Novosibirsk regional vascular center of City Clinical Hospital #1 for the period from 2013 to 2015 was done. We analyzed the annual reports of the regional vascular center, dynamics of cerebrovascular disease patterns, lethality, about the provision of medical care to patients with stroke, the use of high-tech methods of diagnosis and treatment. Ascertain the progress achieved and the perspectives of further improving the quality of care to patients with stroke due to wider use of methods of rehabilitation in the acute stage of stroke.

  19. Transient ventricular dysfunction after an asphyxiation event: stress or hypoxia?

    PubMed

    Valletta, Mary E; Haque, Ikram; Al-Mousily, Faris; Udassi, Jai; Saidi, Arwa

    2008-11-01

    This report of a pediatric patient with acute upper airway obstruction causing asphyxiation emphasizes the need to maintain clinical suspicion for acquired myocardial dysfunction, despite the presumed role of noncardiogenic causes for pulmonary edema after an acute upper airway obstruction. Case report. A tertiary pediatric intensive care unit. A 10-year-old girl with no significant medical history who developed flash pulmonary edema and acute myocardial dysfunction after an acute upper airway obstruction. Serial echocardiograms, exercise stress test, and coronary angiography were performed. Serial pro-brain natriuretic peptide, troponins, and CK-MB levels were also followed. Troponin level normalized approximately 7 days after the acute event. CK-MB and pro-brain natriuretic peptide levels decreased but had not completely normalized by time of discharge. The patient was discharged home 10 days after the event on an anticipated 6-month course of metoprolol without any signs or symptoms of cardiac dysfunction. Myocardial dysfunction is rarely documented in children after an acute upper airway obstruction or an asphyxiation event. Pediatric intensivists and hospitalists should maintain a high degree of clinical suspicion and screen for possible myocardial dysfunction in the pediatric patient with an acute severe hypoxic event especially when accompanied by pulmonary edema. Prompt evaluation ensures appropriate support. Additionally, some role may exist for early adrenergic receptor blockade.

  20. Secoiridoids delivered as olive leaf extract induce acute improvements in human vascular function and reduction of an inflammatory cytokine: a randomised, double-blind, placebo-controlled, cross-over trial.

    PubMed

    Lockyer, Stacey; Corona, Giulia; Yaqoob, Parveen; Spencer, Jeremy P E; Rowland, Ian

    2015-07-14

    The leaves of the olive plant (Olea europaea) are rich in polyphenols, of which oleuropein and hydroxytyrosol (HT) are most characteristic. Such polyphenols have been demonstrated to favourably modify a variety of cardiovascular risk factors. The aim of the present intervention was to investigate the influence of olive leaf extract (OLE) on vascular function and inflammation in a postprandial setting and to link physiological outcomes with absorbed phenolics. A randomised, double-blind, placebo-controlled, cross-over, acute intervention trial was conducted with eighteen healthy volunteers (nine male, nine female), who consumed either OLE (51 mg oleuropein; 10 mg HT), or a matched control (separated by a 4-week wash out) on a single occasion. Vascular function was measured by digital volume pulse (DVP), while blood collected at baseline, 1, 3 and 6 h was cultured for 24 h in the presence of lipopolysaccharide in order to investigate effects on cytokine production. Urine was analysed for phenolic metabolites by HPLC. DVP-stiffness index and ex vivo IL-8 production were significantly reduced (P< 0.05) after consumption of OLE compared to the control. These effects were accompanied by the excretion of several phenolic metabolites, namely HT and oleuropein derivatives, which peaked in urine after 8-24 h. The present study provides the first evidence that OLE positively modulates vascular function and IL-8 production in vivo, adding to growing evidence that olive phenolics could be beneficial for health.

  1. Alcoholism and traumatic subarachnoid hemorrhage: an experimental study on vascular morphology and biomechanics.

    PubMed

    Wang, Haipeng; Yu, Xiaojun; Xu, Guohui; Xu, Guangtao; Gao, Guishan; Xu, Xiaohu

    2011-01-01

    Traumatic subarachnoid hemorrhage (TSAH) related to alcohol abuse is a notable risk factor. Here, we investigated the vascular morphology and biomechanics of TSAH in rat models of acute alcoholic intoxication and chronic alcoholism rats to explore the possible mechanisms of TSAH. Sixty male Sprague-Dawley rats were divided into acute alcoholic intoxication and chronic alcoholism groups. Edible spirituous liquor (56% vol/vol) was intragastrically given (15 mL/kg) once to the rats in the acute group, and given twice daily (8 mL/kg for 2 weeks and 12 mL/kg for another 2 weeks) to rats in the chronic group. A self-made instrument was used to inflict head injury. Whole brain, arterial blood, and thoracic aorta of rats were sampled for morphologic and biomechanical examination. Compared with the acute alcoholic rats, the chronic alcoholic rats showed significant morphologic and biomechanical changes: (1) decreased body weight (p<0.05), (2) higher morbidity and mortality from TSAH (p<0.01), (3) greater mean thickness of vascular wall of subarachnoid small arteries and each layer thickness of thoracic aorta (p<0.05), (4) decreased failure load and corresponding extensibility (60 kPa and limit load) of thoracic aorta, and (5) increased elastic modulus (30 kPa, range in physiologic stress) (p<0.05). Chronic alcoholism can induce the morphologic and biomechanical changes in cerebral vessels and thoracic aorta. The synergistic effect of alcohol abuse and minor blow may be one of the mechanisms of TSAH. High blood pressure from long-term alcohol abuse is also a notable factor.

  2. Identification of the "minimal triangle" and other common event-to-event transitions in conflict and containment incidents.

    PubMed

    Bowers, Len; James, Karen; Quirk, Alan; Wright, Steve; Williams, Hilary; Stewart, Duncan

    2013-07-01

    Although individual conflict and containment events among acute psychiatric inpatients have been studied in some detail, the relationship of these events to each other has not. In particular, little is known about the temporal order of events for individual patients. This study aimed to identify the most common pathways from event to event. A sample of 522 patients was recruited from 84 acute psychiatric wards in 31 hospital locations in London and the surrounding areas during 2009-2010. Data on the order of conflict and containment events were collected for the first two weeks of admission from patients' case notes. Event-to-event transitions were tabulated and depicted diagrammatically. Event types were tested for their most common temporal placing in sequences of events. Most conflict and containment occurs within and between events of the minimal triangle (verbal aggression, de-escalation, and PRN medication), and the majority of these event sequences conclude in no further events; a minority transition to other, more severe, events. Verbal abuse and medication refusal were more likely to start sequences of disturbed behaviour. Training in the prevention and management of violence needs to acknowledge that a gradual escalation of patient behaviour does not always occur. Verbal aggression is a critical initiator of conflict events, and requires more detailed and sustained research on optimal management and prevention strategies. Similar research is required into medication refusal by inpatients.

  3. Age-specific association between blood pressure and vascular and non-vascular chronic diseases in 0·5 million adults in China: a prospective cohort study.

    PubMed

    Lacey, Ben; Lewington, Sarah; Clarke, Robert; Kong, Xiang Ling; Chen, Yiping; Guo, Yu; Yang, Ling; Bennett, Derrick; Bragg, Fiona; Bian, Zheng; Wang, Shaojie; Zhang, Hua; Chen, Junshi; Walters, Robin G; Collins, Rory; Peto, Richard; Li, Liming; Chen, Zhengming

    2018-06-01

    The age-specific association between blood pressure and vascular disease has been studied mostly in high-income countries, and before the widespread use of brain imaging for diagnosis of the main stroke types (ischaemic stroke and intracerebral haemorrhage). We aimed to investigate this relationship among adults in China. 512 891 adults (59% women) aged 30-79 years were recruited into a prospective study from ten areas of China between June 25, 2004, and July 15, 2008. Participants attended assessment centres where they were interviewed about demographic and lifestyle characteristics, and their blood pressure, height, and weight were measured. Incident disease was identified through linkage to local mortality records, chronic disease registries, and claims to the national health insurance system. We used Cox regression analysis to produce adjusted hazard ratios (HRs) relating systolic blood pressure to disease incidence. HRs were corrected for regression dilution to estimate associations with long-term average (usual) systolic blood pressure. During a median follow-up of 9 years (IQR 8-10), there were 88 105 incident vascular and non-vascular chronic disease events (about 90% of strokes events were diagnosed using brain imaging). At ages 40-79 years (mean age at event 64 years [SD 9]), usual systolic blood pressure was continuously and positively associated with incident major vascular disease throughout the range 120-180 mm Hg: each 10 mm Hg higher usual systolic blood pressure was associated with an approximately 30% higher risk of ischaemic heart disease (HR 1·31 [95% CI 1·28-1·34]) and ischaemic stroke (1·30 [1·29-1·31]), but the association with intracerebral haemorrhage was about twice as steep (1·68 [1·65-1·71]). HRs for vascular disease were twice as steep at ages 40-49 years than at ages 70-79 years. Usual systolic blood pressure was also positively associated with incident chronic kidney disease (1·40 [1·35-1·44]) and diabetes (1·14 [1

  4. Modeling the acute health effects of astronauts from exposure to large solar particle events.

    PubMed

    Hu, Shaowen; Kim, Myung-Hee Y; McClellan, Gene E; Cucinotta, Francis A

    2009-04-01

    Radiation exposure from Solar Particle Events (SPE) presents a significant health concern for astronauts for exploration missions outside the protection of the Earth's magnetic field, which could impair their performance and result in the possibility of failure of the mission. Assessing the potential for early radiation effects under such adverse conditions is of prime importance. Here we apply a biologically based mathematical model that describes the dose- and time-dependent early human responses that constitute the prodromal syndromes to consider acute risks from SPEs. We examine the possible early effects on crews from exposure to some historically large solar events on lunar and/or Mars missions. The doses and dose rates of specific organs were calculated using the Baryon radiation transport (BRYNTRN) code and a computerized anatomical man model, while the hazard of the early radiation effects and performance reduction were calculated using the Radiation-Induced Performance Decrement (RIPD) code. Based on model assumptions we show that exposure to these historical events would cause moderate early health effects to crew members inside a typical spacecraft or during extra-vehicular activities, if effective shielding and medical countermeasure tactics were not provided. We also calculate possible even worse cases (double intensity, multiple occurrences in a short period of time, etc.) to estimate the severity, onset and duration of various types of early illness. Uncertainties in the calculation due to limited data on relative biological effectiveness and dose-rate modifying factors for protons and secondary radiation, and the identification of sensitive sites in critical organs are discussed.

  5. Dipyridamole for preventing recurrent ischemic stroke and other vascular events: a meta-analysis of individual patient data from randomized controlled trials.

    PubMed

    Leonardi-Bee, Jo; Bath, Philip M W; Bousser, Marie-Germaine; Davalos, Antoni; Diener, Hans-Christoph; Guiraud-Chaumeil, Bernard; Sivenius, Juhani; Yatsu, Frank; Dewey, Michael E

    2005-01-01

    Results from randomized controlled trials of dipyridamole, given with or without aspirin, for secondary prevention after ischemic stroke or transient ischemic attack (TIA) have given conflicting results. We performed a meta-analysis using individual patient data from relevant randomized controlled trials. Randomized controlled trials involving dipyridamole in patients with previous ischemic stroke or TIA were sought from searches of the Cochrane Library, other electronic databases, references lists, earlier reviews, and contact with the manufacturer of dipyridamole. Individual patient data were merged from 5 of 7 relevant trials involving 11 459 patients. Results were adjusted for age, gender, qualifying event, and history of previous hypertension. Recurrent stroke was reduced by dipyridamole as compared with control (OR, 0.82; 95% CI, 0.68 to 1.00), and by combined aspirin and dipyridamole versus aspirin alone (OR, 0.78; 95% CI, 0.65 to 0.93), dipyridamole alone (OR, 0.74; 95% CI, 0.60 to 0.90), or control (OR, 0.61; 95% CI, 0.51 to 0.71). The point estimates obtained for the comparisons of aspirin and dipyridamole versus control (OR, 0.63; significant) or versus aspirin (OR, 0.88; nonsignificant) were similar if the data from the largest trial, ESPS II (which provided 57% of data), were excluded. Similar findings were observed for nonfatal stroke. The combination of aspirin and dipyridamole also significantly reduced the composite outcome of nonfatal stroke, nonfatal myocardial infarction, and vascular death as compared with aspirin alone (OR, 0.84; 95% CI, 0.72 to 0.97), dipyridamole alone (OR, 0.76; 95% CI, 0.64 to 0.90), or control (OR, 0.66; 95% CI, 0.57 to 0.75). Vascular death was not altered in any group. Dipyridamole, given alone or with aspirin, reduces stroke recurrence in patients with previous ischemic cerebrovascular disease. The combination of aspirin and dipyridamole also reduces the composite of nonfatal stroke, nonfatal myocardial infarction, and

  6. OCT imaging of acute vascular changes following mild traumatic brain injury in mice (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Chico-Calero, Isabel; Shishkov, Milen; Welt, Jonathan; Blatter, Cedric; Vakoc, Benjamin J.

    2016-03-01

    While most people recover completely from mild traumatic brain injuries (mTBIs) and concussions, a subset develop lasting neurological disorders. Understanding the complex pathophysiology of these injuries is critical to developing improved prognostic and therapeutic approaches. Multiple studies have shown that the structure and perfusion of brain vessels are altered after mTBI. It is possible that these vascular injuries contribute to or trigger neurodegeneration. Intravital microscopy and mouse models of TBI offer a powerful platform to study the vascular component of mTBI. Because optical coherence tomography based angiography is based on perfusion contrast and is not significantly degraded by vessel leakage or blood brain barrier disruption, it is uniquely suited to studies of brain perfusion in the setting of trauma. However, existing TBI imaging models require surgical exposure of the brain at the time of injury which conflates TBI-related vascular changes with those caused by surgery. In this work, we describe a modified cranial window preparation based on a flexible, transparent polyurethane membrane. Impact injuries were delivered directly through this membrane, and imaging was performed immediately after injury without the need for additional surgical procedures. Using this model, we demonstrate that mTBI induces a transient cessation of flow in the capillaries and smaller vessels near the injury point. Reperfusion is observed in all animals within 3 hours of injury. This work describes new insight into the transient vascular changes induced by mTBI, and demonstrates more broadly the utility of the OCT/polyurethane window model platform in preclinical studies of mTBI.

  7. Sunitinib-Induced Acute Interstitial Nephritis in a Thrombocytopenic Renal Cell Cancer Patient.

    PubMed

    Azar, Ibrahim; Esfandiarifard, Saghi; Sinai, Pedram; Wazir, Ali; Foulke, Llewellyn; Mehdi, Syed

    2017-01-01

    Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is currently the standard of care for patients with metastatic renal cell carcinoma. Renal adverse events associated with sunitinib include proteinuria, renal insufficiency secondary to focal segmental glomerulosclerosis (FSGS), and thrombotic microangiopathy. We describe the second reported instance of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN), in a challenging case complicated by thrombocytopenia. The case illustrates the importance of early diagnosis and intervention in ensuring long-term recovery from renal complications. Four other cases of AIN reported along with inhibition of the vascular endothelial growth factor (VEGF) by either TKI (sunitinib and sorafenib) or antibodies (bevacizumab) suggest a possible class effect. Given our experience, we recommend monitoring renal function with VEGF inhibition, and in the case of renal failure in the setting of an unclear diagnosis, we recommend prompt biopsy.

  8. Professional liability claims in vascular surgery practice.

    PubMed

    Roche, Enric; Gómez-Durán, Esperanza L; Benet-Travé, Josep; Martin-Fumadó, Carles; Arimany-Manso, Josep

    2014-02-01

    Patient safety is a major concern worldwide, but particularly high rates of adverse events are reported in the surgery setting. Angiology and vascular surgery is of special interest due to the complexity of the pathologies involved and the esthetic component of some of its procedures. In this study we identified the most frequent factors that apply to vascular surgery claims to determine areas of special risk in vascular surgery, with an aim to improve patient safety. We performed a retrospective and descriptive study of the claims pertaining to vascular surgery from the database of the Service of Professional Liability (SRP) of the Official College of Physicians of Barcelona. The time frame of data collection was from 1986 to 2009. We analyzed both the clinical and legal characteristics of the cases. Of the total of 6952 registered claims during the 23-year period, 91 (1.3%) were related to the practice of vascular surgery. Of these, 53.8% were related to venous pathology and 46.1% to arterial pathology. Neurologic damage was the main motive for claims (15.3%), followed by thromboembolic disease (14.2%), burns as a result of cosmetic treatment (12%), and amputation (10.9%). The neurologic damage in relation to vein pathology registered the greatest proportion of cases with professional liability (30.8%), followed by burns (19.2%), forgotten gauze (11.5%), and amputations (11.5%). Angiology and vascular surgery does not seem to be a specialty with a high risk for claims, but complications, such as thromboembolic disease and neurologic damage after varicose vein intervention, do occur and deserve special attention so improvements can be made to patient safety. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Acute effect of L-arginine on hemodynamics and vascular capacitance in the canine pacing model of heart failure.

    PubMed

    Ogilvie, R I; Zborowska-Sluis, D

    1995-09-01

    The effect of L-arginine, 250 mg/kg over 10 min, on hemodynamics and venous function was studied in nine splenectomized dogs under light pentobarbital anesthesia before and after 17 +/- 1 days of rapid right ventricular pacing (RRVP) at 250 beats/min. Chronic RRVP induced mild congestive heart failure with increased mean circulatory filling (Pmcf), right atrial (Pra) and pulmonary capillary wedge pressures (Ppcw), and reduced cardiac output (CO). During the development of heart failure, total vascular compliance assessed from Pmcf-blood volume relationships during circulatory arrest was unchanged, but total vascular capacitance was markedly reduced, with an increase in stressed and reduction in unstressed blood volumes. At baseline but not after RRVP, L-arginine increased CO and reduced pulmonary vascular resistance. There were no significant changes in Pra, Ppcw, or total peripheral resistance. L-Arginine failed to alter total vascular compliance and capacitance or central blood volume in the baseline or failure state. These results do not support the hypothesis that increased Pmcf and reduced total vascular capacitance in the early stages of pacing-induced heart failure are caused by reduced substrate availability for or an endogenous competitive antagonist of NO synthase in venous endothelial cells.

  10. Preoperative and intraoperative predictors of cardiac adverse events after general, vascular, and urological surgery.

    PubMed

    Kheterpal, Sachin; O'Reilly, Michael; Englesbe, Michael J; Rosenberg, Andrew L; Shanks, Amy M; Zhang, Lingling; Rothman, Edward D; Campbell, Darrell A; Tremper, Kevin K

    2009-01-01

    The authors sought to determine the incidence and risk factors for perioperative cardiac adverse events (CAEs) after noncardiac surgery using detailed preoperative and intraoperative hemodynamic data. The authors conducted a prospective observational study at a single university hospital from 2002 to 2006. All American College of Surgeons-National Surgical Quality Improvement Program patients undergoing general, vascular, and urological surgery were included. The CAE outcome definition included cardiac arrest, non-ST elevation myocardial infarction, Q-wave myocardial infarction, and new clinically significant cardiac dysrhythmia within the first 30 postoperative days. Four years of data demonstrated that of 7,740 noncardiac operations, 83 patients (1.1%) experienced a CAE within 30 days. Nine independent predictors were identified (P < or = 0.05): age > or = 68, body mass index > or = 30, emergent surgery, previous coronary intervention or cardiac surgery, active congestive heart failure, cerebrovascular disease, hypertension, operative duration > or = 3.8 h, and the administration of 1 or more units of packed red blood cells intraoperatively. The c-statistic of this model was 0.81 +/- 0.02. Univariate analysis demonstrated that high-risk patients experiencing a CAE were more likely to experience an episode of mean arterial pressure < 50 mmHg (6% vs. 24%, P = 0.02), experience an episode of 40% decrease in mean arterial pressure (26% vs. 53%, P = 0.01), and an episode of heart rate > 100 (22% vs. 34%, P = 0.05). In comparison with current risk stratification indices, the inclusion of intraoperative elements improves the ability to predict a perioperative CAE after noncardiac surgery.

  11. Association of adiponectin with future cardiovascular events in patients after acute myocardial infarction.

    PubMed

    Huang, Shao-Sung; Huang, Po-Hsun; Chen, Ying-Hwa; Chiang, Kuang-Hsing; Chen, Jaw-Wen; Lin, Shing-Jong

    2010-03-31

    There is uncertainty about the association between circulating concentrations of adiponectin and coronary heart disease risk, particularly in patients after acute myocardial infarction (AMI). The goal of this study was to determine whether plasma adiponectin levels could predict future cardiovascular events in patients after AMI, and to elucidate the role of adiponectin in cardioprotection. A total of 102 patients with AMI were enrolled. Plasma adiponectin levels were examined from blood samples collected 18 months after AMI. All subjects were followed-up for 43+/-12 months. The primary endpoint was the combined occurrence of major adverse cardiovascular events (MACE), including rehospitalization due to unstable angina, nonfatal MI, revascularization with percutaneous coronary intervention or coronary artery bypass grafting, ischemic stroke, and cardiovascular death. A total of 30 MACE occurred, including one case of cardiovascular death, five cases of nonfatal MI, and nine cases of ischemic stroke. Patients with MACE had lower plasma adiponectin levels (p=0.013). In addition, adiponectin was positively associated with changes in left ventricular ejection fraction (p=0.005). All patients were divided into a high-adiponectin group (>or=6.46 microg/mL) and a low-adiponectin group (<6.46 microg/mL). The incidence of MACE was significantly reduced in the high-adiponectin group (p=0.021). In multivariate Cox regression analysis that included adiponectin, classical risk factors, and medications, adiponectin was an independent predictor of MACE in patients after AMI (HR, 0.821; 95% CI, 0.691 to 0.974; p=0.024). The results indicate a potential association between plasma adiponectin levels and future cardiovascular events in patients after AMI. Moreover, plasma adiponectin concentrations appear to play a pivotal role in atherothrombosis and cardioprotection.

  12. Antenatal magnesium sulfate exposure and acute cardiorespiratory events in preterm infants.

    PubMed

    De Jesus, Lilia C; Sood, Beena G; Shankaran, Seetha; Kendrick, Douglas; Das, Abhik; Bell, Edward F; Stoll, Barbara J; Laptook, Abbot R; Walsh, Michele C; Carlo, Waldemar A; Sanchez, Pablo J; Van Meurs, Krisa P; Bara, Rebecca; Hale, Ellen C; Newman, Nancy S; Ball, M Bethany; Higgins, Rosemary D

    2015-01-01

    Antenatal magnesium (anteMg) is used for various obstetric indications including fetal neuroprotection. Infants exposed to anteMg may be at risk for respiratory depression and delivery room (DR) resuscitation. The study objective was to compare the risk of acute cardiorespiratory events among preterm infants who were and were not exposed to anteMg. This was a retrospective analysis of prospective data collected in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network's Generic Database from April 1, 2011, through March 31, 2012. The primary outcome was DR intubation or respiratory support at birth or on day 1 of life. Secondary outcomes were invasive mechanical ventilation, hypotension treatment, neonatal morbidities, and mortality. Logistic regression analysis evaluated the risk of primary outcome after adjustment for covariates. We evaluated 1544 infants <29 weeks' gestational age (1091 in anteMg group and 453 in nonexposed group). Mothers in the anteMg group were more likely to have higher education, pregnancy-induced hypertension, and antenatal corticosteroids, while their infants were younger in gestation and weighed less (P < .05). The primary outcome (odds ratio [OR], 1.2; 95% confidence interval [CI], 0.88-1.65) was similar between groups. Hypotension treatment (OR, 0.70; 95% CI, 0.51-0.97) and invasive mechanical ventilation (OR, 0.54; 95% CI, 0.41-0.72) were significantly less in the anteMg group. Among preterm infants age <29 weeks' gestation, anteMg exposure was not associated with an increase in cardiorespiratory events in the early newborn period. The safety of anteMg as measured by the need for DR intubation or respiratory support on day 1 of life was comparable between groups. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Risk Factor Analysis for Mastectomy Skin Flap Necrosis: Implications for Intraoperative Vascular Analysis.

    PubMed

    Reintgen, Christian; Leavitt, Adam; Pace, Elizabeth; Molas-Pierson, Justine; Mast, Bruce A

    2016-06-01

    Skin flap necrosis after mastectomy can be a devastating complication significantly affecting patient outcomes. Routine vascular analysis (fluorescein or laser angiography) of mastectomy skin flaps in all patients has been advocated but is of questionable cost-effectiveness. The purpose of this study was to identify the incidence and causative risk factors for mastectomy skin flap necrosis and thereby calculate the fiscal reality of intraoperative vascular screening. This is an institutional review board-approved retrospective study of all patients from 2007 to 2013 who underwent mastectomy related to breast cancer. Skin flap necrosis was defined as major if it necessitated return to the operating room. Data analysis was done for determination of causative factors of necrosis, including age, body mass index, smoking, previous irradiation, coronary artery disease, chronic obstructive pulmonary disorder, hypertension, gastroesophageal reflux disease, hyperlipidemia, obstructive sleep apnea, asthma, diabetes, thyroid disease, history of lumpectomy, and breast reduction or augmentation. During this time, intraoperative vascular screening was not done. Five hundred eighty-one patients underwent 616 mastectomies with a total of 34 necrotic events (5.5%)-16 major and 18 minor. Analyses via Student t tests, univariate analyses, χ testing, and logistic regression showed that history of smoking was the only patient factor associated with postoperative necrosis (P = 0.008). More frequently represented in the necrosis group, but without statistical significance, are previous lumpectomy (P = 0.069) and immediate reconstruction (P = 0.078).For the entire study period, the actual cost to the hospital for major necrotic events was $7,123.10 or $445.19 for each of the 16 major necrotic events and $209.50 for all 34 necrotic events. Per-patient cost-effective screening would need to be less than $11.54 for all patients, $100.33 for highest risk patients (smokers), and $21.65 for

  14. Biomechanical factors as regulators of biological responses to vascular grafts.

    PubMed

    Fortunato, J E; Glagov, S; Bassiouny, H S

    1999-03-01

    Biomechanical forces have been implicated in the induction and progression of intimal hyperplastic thickening in vein, prosthetic, and endovascular bypass grafts. Graft implantation imposes significant alterations is shear and tensile forces. Such physical forces play an important role in modulating those cellular and molecular events that underlie regulation of vascular healing and adaptation. Characterization of such hemodynamic variables that induce perpetual medial vascular smooth muscle cell proliferation and migration will help in identification of those grafts at risk for occlusion and limited long-term patency and in design of therapeutic strategies that attenuate progressive intimal hyperplasia.

  15. The impact of a focused vascular lower limb arterial duplex (F-VLAD) scan in management decisions for acute limb ischaemia.

    PubMed

    Normahani, Pasha; Aslam, Mohammed; Standfield, Nigel J; Jaffer, Usman

    2017-01-01

    To establish the diagnostic accuracy of a 'focused vascular lower limb arterial duplex scan (F-VLAD)' developed to facilitate rapid decision-making for acute limb ischaemia (ALI). Ten cases of ALI were identified from our patient database; clinical details, history and examination findings were extracted from the clinical notes. Original 'full' duplex ultrasound (DUS) pictorial reports were 're-formatted' to include only anatomical segments included in the 'F-VLAD' scan. The series of 10 reports were emailed to 1741 vascular surgeons. Each recipient received a random mixture of full and F-VLAD scans. Participants were asked regarding next step in management and confidence in decision-making (Likert scale; 1 strongly disagree, 5 strongly agree). The cases were again sent out to the same database and respondents were asked as to the cause of ischaemia (embolic or thrombosis). Eighty-one participants responded to the first survey and 43 participants to the second survey. Participants felt more confident making decisions regarding management using the full duplex report compared to the F-VLAD report (4 (3-4) vs 3 (2-4), median (IQR); p<0.001). However, there was no significant difference in diagnostic accuracy (differentiating embolus from thrombosis) when comparing the F-VLAD and full DUS reports (85.4% vs 88.3%; p=0.461). F-VLAD and 'full' DUS reports had comparable sensitivity (85.1% vs 86.8%), specificity (85.6% vs 89.2%),positive predictive value (PPV) (80.4% vs 81.9%) and negative predictive value (NPV) (89.2% vs 92.2%), respectively. The F-VLAD scan has comparable accuracy to a traditional full DUS in diagnosing the underlying aetiology of ALI. This may facilitate surgeon-performed point-of-care DUS.

  16. Acute Kidney Injury before Dialysis Initiation Predicts Adverse Outcomes in Hemodialysis Patients.

    PubMed

    Lee, Timmy; Shah, Silvi; Leonard, Anthony C; Parikh, Pratik; Thakar, Charuhas V

    2018-06-07

    Acute kidney injury (AKI) is associated with increased morbidity and mortality. Mortality in end-stage renal disease (ESRD) patients is highest during the first year of dialysis. The impact of pre-ESRD AKI events on long-term outcomes in incident ESRD patients remains unknown. We evaluated a retrospective cohort of 47,341 incident hemodialysis patients from the United States Renal Data System with linked Medicare data for at least 2 years prior to hemodialysis initiation. We examined the impact of pre-ESRD AKI events in the 2-year pre-ESRD period on the type of vascular access used at hemodialysis initiation (central venous catheter (CVC) versus arteriovenous access), and 1-year all-cause mortality after initiating hemodialysis. The mean age was 72 ± 11 years. Of the study cohort, 18% initiated hemodialysis with arteriovenous access, and 54% of patients had at least one pre-ESRD AKI event. One-year, all-cause mortality was 32%. Compared to 75% for patients without a pre-ESRD AKI event, 89% of patients with a pre-ESRD AKI event initiated hemodialysis with CVC than arteriovenous access (p < 0.001). A pre-ESRD AKI event was associated with lower adjusted odds of starting hemodialysis with an arteriovenous access (OR 0.47; 95% CI 0.44-0.50, p < 0.001), and higher adjusted odds of 1-year mortality (OR 1.36; 95% CI 1.30-1.42, p < 0.001). An AKI event prior to initiating hemodialysis independently increases the risk of CVC use and predicts 1-year mortality. Improving processes of care after AKI events may improve dialysis outcomes in patients who progress to ESRD. © 2018 S. Karger AG, Basel.

  17. GWOT Vascular Injury Study 2 Supplemental Project: Impact of Prophylactic Fasciotomy

    DTIC Science & Technology

    2016-10-01

    total #) 15 10% 5 7% Overall Average 8.27 9.00 Overall Range 8-9 9-9 3 Mangled Extremity Severity Score: The most widely used lower - limb ...trauma, crush, blunt trauma, burns, and fractures . Each of these injuries places the wounded Service members at risk for developing acute extremity... lower extremity vascular injury will be used to determine fasciotomy rates, wound management, and iatrogenic complications. The impact of injury and

  18. Racial differences in vascular risk factors and outcomes of patients with intracranial atherosclerotic arterial stenosis.

    PubMed

    Waddy, Salina P; Cotsonis, George; Lynn, Michael J; Frankel, Michael R; Chaturvedi, Seemant; Williams, Janice E; Chimowitz, Marc

    2009-03-01

    Atherosclerotic intracranial stenosis is an important cause of stroke in blacks, yet there are limited data on vascular risk factors and outcome. We analyzed the vascular risk factors and outcomes of blacks and whites in the Warfarin versus Aspirin for Symptomatic Intracranial Disease (WASID) trial. Baseline characteristics and outcomes (ischemic stroke, brain hemorrhage, or vascular death combined and ischemic stroke alone) were compared between blacks (n=174) and whites (n=331) using univariate and multivariate analyses. Blacks were significantly (P<0.05) more likely than whites to be/have: female, hypertension history, diabetes history, higher LDL, higher total cholesterol, lower triglycerides, unmarried, unemployed, nonprivate insurance, no insurance, stroke as qualifying event, <70% stenosis, symptomatic anterior circulation vessel, no antithrombotic medication before qualifying event, and no family history of myocardial infarction. Blacks more frequently reached an end point of ischemic stroke, brain hemorrhage or vascular death (28% versus 20%; hazard ratio of 1.49, 95% CI 1.03 to 2.17, P=0.03), had a higher 2-year event rate (0.28 versus 0.19), and reached the end point of ischemic stroke alone (25% versus 16% at 2 years; hazard ratio of 1.62, P=0.017). In multivariate analysis, race was associated with ischemic stroke (P=0.0488) but not with the end point ischemic stroke, brain hemorrhage or vascular death (P=0.188). Blacks with intracranial stenosis are at higher risk of stroke recurrence than whites. This risk warrants additional study of factors contributing to stroke in blacks and highlights the need for aggressive risk factor management in blacks to prevent recurrence.

  19. The Effect of Anthocyanin-Rich Foods or Extracts on Vascular Function in Adults: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

    PubMed Central

    Fairlie-Jones, Lucy; Davison, Kade; Fromentin, Emilie

    2017-01-01

    Anthocyanins are of interest due to their anti-oxidative and vasodilatory properties. Earlier reviews have shown that berries and other anthocyanin rich foods or extracts can improve vascular health, however the effect of anthocyanins on vascular function has not yet been reviewed. To address this gap in the literature, we conducted a systematic review and meta-analysis of randomised-controlled trials examining anthocyanin-rich foods or extracts on measures of vascular reactivity and/or stiffness in adults. Data from 24 studies were pooled as standardized mean difference (SMD) with 95% confidence intervals (CI). Anthocyanin consumption significantly improved flow-mediated dilation (FMD) following acute (SMD: 3.92%, 95% CI: 1.47, 6.38, p = 0.002; I2 = 91.8%) and chronic supplementation (SMD: 0.84%, 95% CI: 0.55, 1.12, p = 0.000; I2 = 62.5%). Pulse wave velocity was improved following acute supplementation only (SMD: −1.27 m/s, 95% CI: −1.96, −0.58, p = 0.000; I2 = 17.8%). These results support the findings of previous reviews that anthocyanin rich foods or extracts may indeed improve vascular health, particularly with respect to vascular reactivity measured by FMD. More research is required to determine the optimal dosage, and the long-term effects of consumption. PMID:28825651

  20. [Expression of cell adhesion molecules in acute leukemia cell].

    PubMed

    Ju, Xiaoping; Peng, Min; Xu, Xiaoping; Lu, Shuqing; Li, Yao; Ying, Kang; Xie, Yi; Mao, Yumin; Xia, Fang

    2002-11-01

    To investigate the role of cell adhesion molecule in the development and extramedullary infiltration (EI) of acute leukemia. The expressions of neural cell adhesion molecule (NCAM) gene, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) genes in 25 acute leukemia patients bone marrow cells were detected by microarray and reverse transcriptase-polymerase chain reaction (RT-PCR). The expressions of NCAM, ICAM-1 and VCAM-1 gene were significantly higher in acute leukemia cells and leukemia cells with EI than in normal tissues and leukemia cells without EI, respectively, both by cDNA microarray and by RT-PCR. The cDNA microarray is a powerful technique in analysis of acute leukemia cells associated genes. High expressions of cell adhesion molecule genes might be correlated with leukemia pathogenesis and infiltration of acute leukemia cell.

  1. Management strategies for neoplastic and vascular brain lesions presenting during pregnancy: A series of 29 patients.

    PubMed

    Pereira, Celestino Esteves; Lynch, Jose Carlos

    2017-01-01

    The occurrence of a brain tumor or intracranial vascular lesion during pregnancy is a rare event, but when it happens, it jeopardizes the lives of both the mother and infant. It also creates challenges of a neurosurgical, obstetric, and ethical nature. A multidisciplinary approach should be used for their care. Between 1986 and 2015, 12 pregnant women diagnosed with brain tumors and 17 women with intracranial vascular lesion underwent treatment at the Neurosurgery Department of the Servidores do Estado Hospital and Rede D'Or/São Luis. The Neurosurgery Department teamed up with Obstetrics Anesthesiology Departments in establishing the procedures. The patients' records, surgical descriptions, imaging studies, and histopathological material were reviewed. Among 12 patients presenting with brain tumors, there were neither operative mortality nor fetal deaths. Among the vascular lesions, aneurysm rupture was responsible for bleeding in 6 instances. Arteriovenous malformation was diagnosed in 7 patients. In this subgroup, the maternal and fetal mortality rates were 11.7% and 23.7%, respectively. We can assert that the association between a brain tumor and vascular lesions with pregnancy is a very unusual event, which jeopardizes both the lives of the mother and infant. It remains incompletely characterized due to the rare nature of these potentially devastating events. Knowing the exact mechanism responsible for the interaction of pregnancy and with these lesions will improve the treatment of these patients.

  2. Safety and clinical efficacy of Onyx for embolization of extracranial head and neck vascular anomalies.

    PubMed

    Thiex, R; Wu, I; Mulliken, J B; Greene, A K; Rahbar, R; Orbach, D B

    2011-01-01

    Onyx was developed for embolization of central nervous system AVMs but is increasingly used extracranially because of its unique physical properties. We review our experience and results with the use of Onyx for the treatment of fast-flow extracranial vascular lesions. We retrospectively analyzed clinical and imaging records of 22 patients who underwent 71 extracranial embolizations from March 2007 through January 2010. The diagnoses were the following: cervicofacial AVM (n = 18), traumatic fistula (n = 3), and vessel laceration (n = 1). In 62 of 71 procedures (87%), Onyx was the sole embolic agent; it was delivered transarterially in 67/71 and percutaneously in 4/71 procedures. Clinical goals included amelioration of pain and control of bleeding. The clinical efficacy of embolization was judged by symptom control, and adverse events were assessed by clinical examination and history, both postembolization and 4 weeks postprocedure. Cessation of acute bleeding was achieved in 13/14 cases, with 1 case of immediate recurrent massive epistaxis prompting reintubation and further embolization. Control of subacute bleeding episodes and pain was achieved for all patients. Following staged embolization, 7 patients underwent surgical resection without significant blood loss. Surgeons reported high satisfaction with the intraoperative handling properties of Onyx. Transient swelling, local tenderness, or numbness was encountered after 7 procedures. There were no stuck catheters, vessel dissections, or vessel ruptures and no skin discoloration. Staged Onyx embolization was clinically efficacious in managing extracranial fast-flow vascular malformations and lesions, with low associated morbidity.

  3. The Interaction Between IGF-1, Atherosclerosis and Vascular Aging

    PubMed Central

    Higashi, Yusuke; Quevedo, Henry C.; Tiwari, Summit; Sukhanov, Sergiy; Shai, Shaw-Yung; Anwar, Asif; Delafontaine, Patrice

    2014-01-01

    The process of vascular aging encompasses alterations in the function of endothelial (EC) and vascular smooth muscle cells (VSMCs) via oxidation, inflammation, cell senescence and epigenetic modifications, increasing the probability of atherosclerosis. Aged vessels exhibit decreased endothelial antithrombogenic properties, increased reactive oxygen species (ROS) generation and inflammatory signaling, increased migration of VSMCs to the subintimal space, impaired angiogenesis and increased elastin degradation. The key initiating step in atherogenesis is subendothelial accumulation of apolipoprotein-B containing low density lipoproteins resulting in activation of endothelial cells and recruitment of monocytes. Activated endothelial cells secrete “chemokines” that interact with cognate chemokine receptors on monocytes and promote directional migration. Recruitment of immune cells establishes a pro-inflammatory status, further causing elevated oxidative stress, which in turn triggers a series of events including apoptotic or necrotic death of vascular and non-vascular cells. Increased oxidative stress is also considered to be a key factor in mechanisms of aging-associated changes in tissue integrity and function. Experimental evidence indicates that insulin-like growth factor-1 (IGF-1) exerts anti-oxidant, anti-inflammatory and pro-survival effects on the vasculature, reducing atherosclerotic plaque burden and promoting features of atherosclerotic plaque stability. PMID:24943302

  4. Saturated phosphatidic acids mediate saturated fatty acid-induced vascular calcification and lipotoxicity.

    PubMed

    Masuda, Masashi; Miyazaki-Anzai, Shinobu; Keenan, Audrey L; Okamura, Kayo; Kendrick, Jessica; Chonchol, Michel; Offermanns, Stefan; Ntambi, James M; Kuro-O, Makoto; Miyazaki, Makoto

    2015-10-26

    Recent evidence indicates that saturated fatty acid-induced (SFA-induced) lipotoxicity contributes to the pathogenesis of cardiovascular and metabolic diseases; however, the molecular mechanisms that underlie SFA-induced lipotoxicity remain unclear. Here, we have shown that repression of stearoyl-CoA desaturase (SCD) enzymes, which regulate the intracellular balance of SFAs and unsaturated FAs, and the subsequent accumulation of SFAs in vascular smooth muscle cells (VSMCs), are characteristic events in the development of vascular calcification. We evaluated whether SMC-specific inhibition of SCD and the resulting SFA accumulation plays a causative role in the pathogenesis of vascular calcification and generated mice with SMC-specific deletion of both Scd1 and Scd2. Mice lacking both SCD1 and SCD2 in SMCs displayed severe vascular calcification with increased ER stress. Moreover, we employed shRNA library screening and radiolabeling approaches, as well as in vitro and in vivo lipidomic analysis, and determined that fully saturated phosphatidic acids such as 1,2-distearoyl-PA (18:0/18:0-PA) mediate SFA-induced lipotoxicity and vascular calcification. Together, these results identify a key lipogenic pathway in SMCs that mediates vascular calcification.

  5. [Vascular Lesions of Vocal Folds - Part 2: Perpendicular Vascular Lesions].

    PubMed

    Arens, C; Glanz, H; Voigt-Zimmermann, S

    2015-11-01

    The present work aims at a systematic pathogenetic description of perpendicular vascular changes in the vocal folds. Unlike longitudinal vascular changes, like ectasia and meander, perpendicular vascular changes can be observed in bening lesions. They predominantly occur as typical vascular loops in exophytic lesions, especially in recurrent respiratory papillomatosis (RRP), pre-cancerous and cancerous diseases of the larynx and vocal folds. Neoangiogenesis is caused by an epithelial growth stimulus in the early phase of cancerous genesis. In RRP the VVC impress by a single, long vessel loop with a narrow angle turning point in the each single papilla of the papilloma. In pre- and cancerous lesions the vascular loop is located directly underneath the epithelium. During progressive tumor growth, vascular loops develop an increasingly irregular, convoluted, spirally shape. The arrangement of the vascular loops is primarily still symmetrical. In the preliminary stage of tumor development occurs by neoangiogenesis to a microvascular compression. In advanced vocal fold carcinoma the regular vascular vocal fold structure is destroyed. The various stages of tumor growth are also characterized by typical primary epithelial and secondary connective tissue changes. The characteristic triad of vascular, epithelial and connective tissue changes therefore plays an important role in differential diagnosis. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Engaged patients, engaged partnerships: singles and partners dealing with an acute cardiac event.

    PubMed

    Bertoni, Anna; Donato, Silvia; Graffigna, Guendalina; Barello, Serena; Parise, Miriam

    2015-01-01

    A few studies examine patients' (and partners') individual and relational functioning after an acute cardiac event and no research focuses on the individual and relational factors associated with the patient's engagement in his/her disease management. The present study aimed at exploring these variables in male and female patients as well as their partners. We pursued our objectives by taking advantage of a dyadic research design that involved both partners in the data collection, when present, and by including women patients in the sample. Findings showed that patients in a couple, compared to single patients, perceive that their illness had less serious consequences for their life and they were more engaged in their health care; that patients and partners showed comparable levels of distress; and that less depressed, more confident, and better informed patients were more likely to actively engage in their treatment. Findings are discussed in light of their implications for clinical practice.

  7. Short Sleep Duration, Obstructive Sleep Apnea, Shiftwork, and the Risk of Adverse Cardiovascular Events in Patients After an Acute Coronary Syndrome.

    PubMed

    Barger, Laura K; Rajaratnam, Shantha M W; Cannon, Christopher P; Lukas, Mary Ann; Im, KyungAh; Goodrich, Erica L; Czeisler, Charles A; O'Donoghue, Michelle L

    2017-10-10

    It is unknown whether short sleep duration, obstructive sleep apnea, and overnight shift work are associated with the risk of recurrent cardiovascular events in patients after an acute coronary syndrome. SOLID-TIMI 52 (The Stabilization of PLaques UsIng Darapladib-Thrombolysis in Myocardial Infarction 52 Trial) was a multinational, double-blind, placebo-controlled trial that enrolled 13 026 patients ≤30 days of acute coronary syndrome. At baseline, all patients were to complete the Berlin questionnaire to assess risk of obstructive sleep apnea and a sleep and shift work survey. Median follow-up was 2.5 years. The primary outcome was major coronary events (MCE; coronary heart disease death, myocardial infarction, or urgent revascularization). Cox models were adjusted for clinical predictors. Patients who reported <6 hours sleep per night had a 29% higher risk of MCE (adjusted hazard ratio, 1.29; 95% confidence interval, 1.12-1.49; P <0.001) compared with those with longer sleep. Patients who screened positive for obstructive sleep apnea had a 12% higher risk of MCE (1.12; 1.00-1.24; P =0.04) than those who did not screen positive. Overnight shift work (≥3 night shifts/week for ≥1 year) was associated with a 15% higher risk of MCE (1.15; 1.03-1.29; P =0.01). A step-wise increase in cardiovascular risk was observed for individuals with more than 1 sleep-related risk factor. Individuals with all 3 sleep-related risk factors had a 2-fold higher risk of MCE (2.01; 1.49-2.71; P <0.0001). Short sleep duration, obstructive sleep apnea, and overnight shift work are under-recognized as predictors of adverse outcomes after acute coronary syndrome. Increased efforts should be made to identify, treat, and educate patients about the importance of sleep for the potential prevention of cardiovascular events. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01000727. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  8. Hydrophobic cyanine dye-doped micelles for optical in vivo imaging of plasma leakage and vascular disruption.

    PubMed

    Botz, Bálint; Bölcskei, Kata; Kemény, Ágnes; Sándor, Zoltán; Tékus, Valéria; Sétáló, György; Csepregi, Janka; Mócsai, Attila; Pintér, Erika; Kollár, László; Helyes, Zsuzsanna

    2015-01-01

    Vascular leakage is an important feature of various disease conditions. In vivo optical imaging provides a great opportunity for the evaluation of this phenomenon. In the present study, we focus on the development and validation of a near-infrared (NIR) imaging formula to allow reliable, cost-efficient evaluation of vascular leakage in diverse species using the existing small-animal fluorescence imaging technology. IR-676, a moderately hydrophobic NIR cyanine dye, was doped into self-assembling aqueous micelles using a widely employed and safe nonionic emulsifier (Kolliphor HS 15), and was tested in several acute and chronic inflammatory disease models in both mice and rats. The imaging formula is stable and exerts no acute toxic effects in vitro. It accumulated specifically in the inflamed regions in all models, which could be demonstrated by both conventional epifluorescence imaging, and fluorescence tomography both as a standalone technique and also by merging it with computed tomography scans. Ex vivo verification of dye accumulation by confocal fluorescence microscopy was also possible. The present formula allows sensitive and specific detection of inflammatory plasma leakage in diverse models. Its potential for imaging larger animals was also demonstrated. IR-676-doped micelles offer an excellent opportunity to image inflammatory vascular leakage in various models and species.

  9. The Incidence and Predictors of Early- and Mid-Term Clinically Relevant Neurological Events After Transcatheter Aortic Valve Replacement in Real-World Patients.

    PubMed

    Bosmans, Johan; Bleiziffer, Sabine; Gerckens, Ulrich; Wenaweser, Peter; Brecker, Stephen; Tamburino, Corrado; Linke, Axel

    2015-07-21

    Transcatheter aortic valve replacement (TAVR) enables treatment of high-risk patients with symptomatic aortic stenosis without open-heart surgery; however, the benefits are mitigated by the potential for neurological events. This study sought to determine the timing and causes of clinically relevant neurological events after self-expandable TAVR. We enrolled 1,015 patients, of whom 996 underwent TAVR with a self-expandable system at 44 TAVR-experienced centers in Europe, Colombia, and Israel. Neurological events were evaluated for 3 distinct time periods: periprocedural (0 to 1 days post TAVR); early (2 to 30 days); and late (31 to 730 days). In this real-world study, neurological events were first referred to the site neurologist and then reviewed by an independent neurologist. The overall stroke rate was 1.4% through the first day post-procedure, 3.0% at 30 days, and 5.6% at 2 years. There were no significant predictors of periprocedural stroke or stroke/transient ischemic attack (TIA) combined. Significant predictors of early stroke were acute kidney injury (p = 0.03), major vascular complication (p = 0.04), and female sex (p = 0.04). For stroke/TIA combined, prior atrial fibrillation (p = 0.03) and major vascular complication (p = 0.009) were predictive. Coronary artery bypass graft surgery was the only significant predictor of late stroke (p = 0.007) or late stroke/TIA (p = 0.06). Treatment of high-risk patients with aortic stenosis using a self-expandable system was associated with a low stroke rate at short- and long-term follow-up. Multivariable predictors of clinically relevant neurological events differed on the basis of the timing after TAVR. (CoreValve Advance International Post Market Study; NCT01074658). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  10. Early Vascular Ageing - A Concept in Development.

    PubMed

    M Nilsson, Peter

    2015-04-01

    Cardiovascular disease (CVD) is a prevalent condition in the elderly, often associated with metabolic disturbance and type 2 diabetes. For a number of years, research dedicated to understand atherosclerosis dominated, and for many good reasons, this pathophysiological process being proximal to the CVD events. In recent years, research has been devoted to an earlier stage of vascular pathology named arteriosclerosis (arterial stiffness) and the new concept of early vascular ageing (EVA), developed by a group of mostly European researchers. This overview describes recent developments in research dedicated to EVA and new emerging aspects found in studies of families at high cardiovascular risk. There are new aspects related to genetics, telomere biology and the role of gut microbiota. However, there is still no unifying definition available of EVA and no direct treatment, but rather only recommendations for conventional cardiovascular risk factor control. New interventions are being developed - not only new antihypertensive drugs, but also new drugs for vascular protection - the selective angiotensin-II (AT2) agonist Compound 21 (C21). Human studies are eagerly awaited. Even new functional food products could have the potential to positively influence cardiometabolic regulation, to be confirmed.

  11. Linking vascular disorders and Alzheimer’s disease: Potential involvement of BACE1

    PubMed Central

    Cole, Sarah L.; Vassar, Robert

    2012-01-01

    The etiology of Alzheimer’s disease (AD) remains unknown. However, specific risk factors have been identified, and aging is the strongest AD risk factor. The majority of cardiovascular events occur in older people and a close relationship between vascular disorders and AD exists. Amyloid plaques, composed of the beta amyloid peptide (Aβ), are hallmark lesions in AD and evidence indicates that Aβ plays a central role in AD pathophysiology. The BACE1 enzyme is essential for Aβ generation, and BACE1 levels are elevated in AD brain. The cause(s) of this BACE1 elevation remains undetermined. Here we review the potential contribution of vascular disease to AD pathogenesis. We examine the putative vasoactive properties of Aβ and how the cellular changes associated with vascular disease may elevate BACE1 levels. Despite increasing evidence, the exact role(s) vascular disorders play in AD remains to be determined. However, given that vascular diseases can be addressed by lifestyle and pharmacologic interventions, the potential benefits of these therapies in delaying the clinical appearance and progression of AD may warrant investigation. PMID:18289733

  12. China Patient-centered Evaluative Assessment of Cardiac Events Prospective Study of Acute Myocardial Infarction: Study Design.

    PubMed

    Li, Jing; Dreyer, Rachel P; Li, Xi; Du, Xue; Downing, Nicholas S; Li, Li; Zhang, Hai-Bo; Feng, Fang; Guan, Wen-Chi; Xu, Xiao; Li, Shu-Xia; Lin, Zhen-Qiu; Masoudi, Frederick A; Spertus, John A; Krumholz, Harlan M; Jiang, Li-Xin

    2016-01-05

    Despite the rapid growth in the incidence of acute myocardial infarction (AMI) in China, there is limited information about patients' experiences after AMI hospitalization, especially on long-term adverse events and patient-reported outcomes (PROs). The China Patient-centered Evaluative Assessment of Cardiac Events (PEACE)-Prospective AMI Study will enroll 4000 consecutive AMI patients from 53 diverse hospitals across China and follow them longitudinally for 12 months to document their treatment, recovery, and outcomes. Details of patients' medical history, treatment, and in-hospital outcomes are abstracted from medical charts. Comprehensive baseline interviews are being conducted to characterize patient demographics, risk factors, presentation, and healthcare utilization. As part of these interviews, validated instruments are administered to measure PROs, including quality of life, symptoms, mood, cognition, and sexual activity. Follow-up interviews, measuring PROs, medication adherence, risk factor control, and collecting hospitalization events are conducted at 1, 6, and 12 months after discharge. Supporting documents for potential outcomes are collected for adjudication by clinicians at the National Coordinating Center. Blood and urine samples are also obtained at baseline, 1- and 12-month follow-up. In addition, we are conducting a survey of participating hospitals to characterize their organizational characteristics. The China PEACE-Prospective AMI study will be uniquely positioned to generate new information regarding patient's experiences and outcomes after AMI in China and serve as a foundation for quality improvement activities.

  13. Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils

    NASA Astrophysics Data System (ADS)

    Wang, Zhenjia; Li, Jing; Cho, Jaehyung; Malik, Asrar B.

    2014-03-01

    Inflammatory diseases such as acute lung injury and ischaemic tissue injury are caused by the adhesion of a type of white blood cell--polymorphonuclear neutrophils--to the lining of the circulatory system or vascular endothelium and unchecked neutrophil transmigration. Nanoparticle-mediated targeting of activated neutrophils on vascular endothelial cells at the site of injury may be a useful means of directly inactivating neutrophil transmigration and hence mitigating vascular inflammation. Here, we report a method employing drug-loaded albumin nanoparticles, which efficiently deliver drugs into neutrophils adherent to the surface of the inflamed endothelium. Using intravital microscopy of tumour necrosis factor-α-challenged mouse cremaster post-capillary venules, we demonstrate that fluorescently tagged albumin nanoparticles are largely internalized by neutrophils adherent to the activated endothelium via cell surface Fcɣ receptors. Administration of albumin nanoparticles loaded with the spleen tyrosine kinase inhibitor, piceatannol, which blocks `outside-in' β2 integrin signalling in leukocytes, detached the adherent neutrophils and elicited their release into the circulation. Thus, internalization of drug-loaded albumin nanoparticles into neutrophils inactivates the pro-inflammatory function of activated neutrophils, thereby offering a promising approach for treating inflammatory diseases resulting from inappropriate neutrophil sequestration and activation.

  14. Targeted modulation of reactive oxygen species in the vascular endothelium.

    PubMed

    Shuvaev, Vladimir V; Muzykantov, Vladimir R

    2011-07-15

    'Endothelial cells lining vascular luminal surface represent an important site of signaling and injurious effects of reactive oxygen species (ROS) produced by other cells and endothelium itself in ischemia, inflammation and other pathological conditions. Targeted delivery of ROS modulating enzymes conjugated with antibodies to endothelial surface molecules (vascular immunotargeting) provides site-specific interventions in the endothelial ROS, unattainable by other formulations including PEG-modified enzymes. Targeting of ROS generating enzymes (e.g., glucose oxidase) provides ROS- and site-specific models of endothelial oxidative stress, whereas targeting of antioxidant enzymes SOD and catalase offers site-specific quenching of superoxide anion and H(2)O(2). These targeted antioxidant interventions help to clarify specific role of endothelial ROS in vascular and pulmonary pathologies and provide basis for design of targeted therapeutics for treatment of these pathologies. In particular, antibody/catalase conjugates alleviate acute lung ischemia/reperfusion injury, whereas antibody/SOD conjugates inhibit ROS-mediated vasoconstriction and inflammatory endothelial signaling. Encapsulation in protease-resistant, ROS-permeable carriers targeted to endothelium prolongs protective effects of antioxidant enzymes, further diversifying the means for targeted modulation of endothelial ROS. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Design and baseline data from the Gratitude Research in Acute Coronary Events (GRACE) study

    PubMed Central

    Huffman, Jeff C.; Beale, Eleanor E.; Beach, Scott R.; Celano, Christopher M.; Belcher, Arianna M.; Moore, Shannon V.; Suarez, Laura; Gandhi, Parul U.; Motiwala, Shweta R.; Gaggin, Hanna; Januzzi, James L.

    2015-01-01

    Background Positive psychological constructs, especially optimism, have been linked with superior cardiovascular health. However, there has been minimal study of positive constructs in patients with acute coronary syndrome (ACS), despite the prevalence and importance of this condition. Furthermore, few studies have examined multiple positive psychological constructs and multiple cardiac-related outcomes within the same cohort to determine specifically which positive construct may affect a particular cardiac outcome. Materials and methods The Gratitude Research in Acute Coronary Events (GRACE) study examines the association between optimism/gratitude 2 weeks post-ACS and subsequent clinical outcomes. The primary outcome measure is physical activity at 6 months, measured via accelerometer, and key secondary outcome measures include levels of prognostic biomarkers and rates of nonelective cardiac rehospitalization at 6 months. These relationships will be analyzed using multivariate linear regression, controlling for sociodemographic, medical, and negative psychological factors; associations between baseline positive constructs and subsequent rehospitalizations will be assessed via Cox regression. Results Overall, 164 participants enrolled and completed the baseline 2-week assessment; the cohort had a mean age of 61.5 +/− 10.5 years and was 84% men; this was the first ACS for 58% of participants. Conclusion The GRACE study will determine whether optimism and gratitude are prospectively and independently associated with physical activity and other critical outcomes in the 6 months following an ACS. If these constructs are associated with superior outcomes, this may highlight the importance of these constructs as independent prognostic factors post-ACS. PMID:26166171

  16. Design and baseline data from the Gratitude Research in Acute Coronary Events (GRACE) study.

    PubMed

    Huffman, Jeff C; Beale, Eleanor E; Beach, Scott R; Celano, Christopher M; Belcher, Arianna M; Moore, Shannon V; Suarez, Laura; Gandhi, Parul U; Motiwala, Shweta R; Gaggin, Hanna; Januzzi, James L

    2015-09-01

    Positive psychological constructs, especially optimism, have been linked with superior cardiovascular health. However, there has been minimal study of positive constructs in patients with acute coronary syndrome (ACS), despite the prevalence and importance of this condition. Furthermore, few studies have examined multiple positive psychological constructs and multiple cardiac-related outcomes within the same cohort to determine specifically which positive construct may affect a particular cardiac outcome. The Gratitude Research in Acute Coronary Events (GRACE) study examines the association between optimism/gratitude 2weeks post-ACS and subsequent clinical outcomes. The primary outcome measure is physical activity at 6months, measured via accelerometer, and key secondary outcome measures include levels of prognostic biomarkers and rates of nonelective cardiac rehospitalization at 6months. These relationships will be analyzed using multivariable linear regression, controlling for sociodemographic, medical, and negative psychological factors; associations between baseline positive constructs and subsequent rehospitalizations will be assessed via Cox regression. Overall, 164 participants enrolled and completed the baseline 2-week assessment; the cohort had a mean age of 61.5+/?10.5years and was 84% men; this was the first ACS for 58% of participants. The GRACE study will determine whether optimism and gratitude are prospectively and independently associated with physical activity and other critical outcomes in the 6months following an ACS. If these constructs are associated with superior outcomes, this may highlight the importance of these constructs as independent prognostic factors post-ACS. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Mitochondrial Oxidative Stress, Mitochondrial DNA Damage and Their Role in Age-Related Vascular Dysfunction

    PubMed Central

    Mikhed, Yuliya; Daiber, Andreas; Steven, Sebastian

    2015-01-01

    The prevalence of cardiovascular diseases is significantly increased in the older population. Risk factors and predictors of future cardiovascular events such as hypertension, atherosclerosis, or diabetes are observed with higher frequency in elderly individuals. A major determinant of vascular aging is endothelial dysfunction, characterized by impaired endothelium-dependent signaling processes. Increased production of reactive oxygen species (ROS) leads to oxidative stress, loss of nitric oxide (•NO) signaling, loss of endothelial barrier function and infiltration of leukocytes to the vascular wall, explaining the low-grade inflammation characteristic for the aged vasculature. We here discuss the importance of different sources of ROS for vascular aging and their contribution to the increased cardiovascular risk in the elderly population with special emphasis on mitochondrial ROS formation and oxidative damage of mitochondrial DNA. Also the interaction (crosstalk) of mitochondria with nicotinamide adenosine dinucleotide phosphate (NADPH) oxidases is highlighted. Current concepts of vascular aging, consequences for the development of cardiovascular events and the particular role of ROS are evaluated on the basis of cell culture experiments, animal studies and clinical trials. Present data point to a more important role of oxidative stress for the maximal healthspan (healthy aging) than for the maximal lifespan. PMID:26184181

  18. Risk factors and prevention of vascular complications in polycythemia vera.

    PubMed

    Barbui, T; Finazzi, G

    1997-01-01

    Risk factors for vascular complications in polycythemia vera (PV) include laboratory and clinical findings. Among laboratory values, the hematocrit has been clearly associated with thrombosis, particularly in the cerebral circulation. Platelet count is a possible but not yet clearly established predictor of vascular complications. Platelet function tests are of little help in prognostic evaluation because most attempts to correlate these abnormalities with clinical events have been disappointing. Clinical predictors of thrombosis include increasing age and a previous history of vascular events. Identifying risk factors for thrombosis is important to initiate therapy. Phlebotomy is associated with an increased incidence of thrombosis in the first 3 to 5 years, whereas chemotherapy may induce a higher risk of secondary malignancies after 7 to 10 years of follow-up. New cytoreductive drugs virtually devoid of mutagenic risk include interferon-alpha and anagrelide, but their role in reducing thrombotic complications remains to be demonstrated. Antithrombotic drugs, such as aspirin, are frequently used in PV, despite doubts regarding safety and efficacy. Two recent studies from the Gruppo Italiano Studio Policitemia Vera (GISP) assessed the rate of major thrombosis as well as the tolerability of low-dose aspirin in PV patients. These investigations created a favorable scenario for launching a European collaborative clinical trial (ECLAP study) aimed at testing the efficacy of low-dose aspirin in preventing thrombosis and prolonging survival in patients with PV.

  19. Acute and chronic effects of flavanol-rich cocoa on vascular function in subjects with coronary artery disease: a randomized double-blind placebo-controlled study.

    PubMed

    Farouque, H M Omar; Leung, Michael; Hope, Sarah A; Baldi, Mauro; Schechter, Clyde; Cameron, James D; Meredith, Ian T

    2006-07-01

    Evidence suggests that flavonoid-containing diets reduce cardiovascular risk, but the mechanisms responsible are unclear. In the present study, we sought to determine the effect of flavanol-rich cocoa on vascular function in individuals with CAD (coronary artery disease). Forty subjects (61+/-8 years; 30 male) with CAD were recruited to a 6-week randomized double-blind placebo-controlled study. Subjects consumed either a flavanol-rich chocolate bar and cocoa beverage daily (total flavanols, 444 mg/day) or matching isocaloric placebos daily (total flavanols, 19.6 mg/day) for 6 weeks. Brachial artery FMD (flow-mediated dilation) and SAC (systemic arterial compliance) were assessed at baseline, 90 min following the first beverage and after 3 and 6 weeks of daily consumption. Soluble cellular adhesion molecules and FBF (forearm blood flow) responses to ACh (acetylcholine chloride; 3-30 microg/min) and SNP (sodium nitroprusside; 0.3-3 microg/min) infusions, forearm ischaemia and isotonic forearm exercise were assessed at baseline and after 6 weeks. FMD, SAC and FBF responses did not differ between groups at baseline. No acute or chronic changes in FMD or SAC were seen in either group. No difference in soluble cellular adhesion molecules, FBF responses to ischaemia, exercise, SNP or ACh was seen in the group receiving flavanol-rich cocoa between baseline and 6 weeks. These data suggest that over a 6-week period, flavanol-rich cocoa does not modify vascular function in patients with established CAD.

  20. Treating vascular lesions.

    PubMed

    Astner, Susanne; Anderson, R Rox

    2005-01-01

    The treatment of acquired vascular lesions is one of the most commonly requested and performed cutaneous laser procedures. Furthermore, every year, 40,000 children are born in the United States each with congenital vascular lesions and malformations. Laser treatment of vascular lesion is based on the principle of selective photothermolysis, conceived in the 1980s. A variety of different lasers and light sources have since been used in the treatment of vascular lesions: lasers with wavelengths between green and yellow, near infrared lasers, and broadband light sources. Despite limitations, this remains the treatment of choice today. This publication addresses acquired and congenital vascular lesions as different entities and proposes a separation of vascular lesions into those that can easily be treated from those where clearance is difficult. Different treatment modalities and the various endpoints of individual vascular lesions will be discussed.

  1. Endothelial mechanotransduction proteins and vascular function are altered by dietary sucrose supplementation in healthy young male subjects.

    PubMed

    Gliemann, Lasse; Rytter, Nicolai; Lindskrog, Mads; Slingsby, Martina H Lundberg; Åkerström, Thorbjörn; Sylow, Lykke; Richter, Erik A; Hellsten, Ylva

    2017-08-15

    Mechanotransduction in endothelial cells is a central mechanism in the regulation of vascular tone and vascular remodelling Mechanotransduction and vascular function may be affected by high sugar levels in plasma because of a resulting increase in oxidative stress and increased levels of advanced glycation end-products (AGE). In healthy young subjects, 2 weeks of daily supplementation with 3 × 75 g of sucrose was found to reduce blood flow in response to passive lower leg movement and in response to 12 W of knee extensor exercise. This vascular impairment was paralleled by up-regulation of platelet endothelial cell adhesion molecule (PECAM)-1, endothelial nitric oxide synthase, NADPH oxidase and Rho family GTPase Rac1 protein expression, an increased basal phosphorylation status of vascular endothelial growth factor receptor 2 and a reduced phosphorylation status of PECAM-1. There were no measurable changes in AGE levels. The findings of the present study demonstrate that daily high sucrose intake markedly affects mechanotransduction proteins and has a detrimental effect on vascular function. Endothelial mechanotransduction is important for vascular function but alterations and activation of vascular mechanosensory proteins have not been investigated in humans. In endothelial cell culture, simple sugars effectively impair mechanosensor proteins. To study mechanosensor- and vascular function in humans, 12 young healthy male subjects supplemented their diet with 3 × 75 g sucrose day -1 for 14 days in a randomized cross-over design. Before and after the intervention period, the hyperaemic response to passive lower leg movement and active knee extensor exercise was determined by ultrasound doppler. A muscle biopsy was obtained from the thigh muscle before and after acute passive leg movement to allow assessment of protein amounts and the phosphorylation status of mechanosensory proteins and NADPH oxidase. The sucrose intervention led to a reduced flow

  2. Ambient air pollutants and acute case-fatality of cerebro-cardiovascular events: Takashima Stroke and AMI Registry, Japan (1988-2004).

    PubMed

    Turin, Tanvir Chowdhury; Kita, Yoshikuni; Rumana, Nahid; Nakamura, Yasuyuki; Ueda, Kayo; Takashima, Naoyuki; Sugihara, Hideki; Morita, Yutaka; Ichikawa, Masaharu; Hirose, Kunihiko; Nitta, Hiroshi; Okayama, Akira; Miura, Katsuyuki; Ueshima, Hirotsugu

    2012-01-01

    Apart from the conventional risk factors, cerebro-cardiovascular disease (CVD) are also reported to be associated with air pollution, thus lowering the level of exposure might contribute in prevention activities to reduce the associated adverse outcomes. Though few studies conducted in Japan have reported on the CVD mortality but none have explored the effect of air pollutant exposure on the acute case-fatality of CVD. We investigated the effects of air pollution exposure on acute case-fatality of stroke and acute myocardial infarction (AMI) in a setting where pollutant levels are rather low. We leveraged the data from the Takashima Stroke and AMI Registry, which covers a population of approximately 55,000 in Takashima County located in central Japan. The study period of 6,210 days (16 years, leap years also taken into account) were divided into quartiles of daily average pollutant concentration; suspended particulate matter (SPM), sulfur dioxide (SO(2)), nitrogen dioxide (NO(2)), and photochemical oxidants (Ox). The stroke and AMI events were categorized to corresponding quartiles based on the pollution levels of the onset day. To study the effects of air pollutants, we estimated the fatality rate ratio across quartiles of the pollutants where the lowest quartile served as the reference. There were 307 (men: 153 and women: 154) fatal stroke cases within 28 days of onset among the 2,038 first ever stroke during 1988-2004. In the same period, there were 142 (men: 94 and women: 54) fatal AMI cases within 28 days of onset among the 429 first ever AMI events. The mean of the measured pollutant levels were as follows: SPM 26.9 µg/m(3), SO(2) 3.9 ppb, NO(2) 16.0 ppb, and Ox 28.4 ppb. Among the pollutants, higher levels of NO(2) showed increased fatality risk. In multi-pollutant model, the highest quartile of NO(2) was associated with 60% higher stroke case-fatality risk in comparison to lowest quartile of NO(2). In the fully adjusted model the fatality-rate ratio was 1

  3. Mitochondria control acute and chronic responses to hypoxia.

    PubMed

    McElroy, G S; Chandel, N S

    2017-07-15

    There are numerous mechanisms by which mammals respond to hypoxia. These include acute changes in pulmonary arterial tone due to smooth muscle cell contraction, acute increases in respiration triggered by the carotid body chemosensory cells, and chronic changes such as induction of red blood cell proliferation and angiogenesis by hypoxia inducible factor targets erythropoietin and vascular endothelial growth factor, respectively. Mitochondria account for the majority of oxygen consumption in the cell and have recently been appreciated to serve as signaling organelles required for the initiation or propagation of numerous homeostatic mechanisms. Mitochondria can influence cell signaling by production of reactive oxygen species and metabolites. Here we review recent evidence that mitochondrial signals can imitate acute and chronic hypoxia responses. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. [Vascular lesions of vocal folds--part 1: horizontal vascular lesions].

    PubMed

    Voigt-Zimmermann, S; Arens, C

    2014-12-01

    In recent decades, the endoscopic methods and technologies for laryngeal examination have improved so much that not only epithelial changes, but also vascular changes are recognizable at earlier stages. When comparing newer and older literature, the associated increasingly differentiated descriptions of such visible vascular changes of the vocal folds lead to terminological blurring and shifts of meaning. This complicates the technical-scientific discourse. The aim of the present work is a theoretical and conceptual clarification of early vascular changes of vocal folds. Horizontal changes of benigne vascular diseases, e. g. vessel ectasia, meander, increasing number and branching of vessels, change of direction may develop in to manifest vascular lesions, like varicosis, polyps and in case of ruptures to haemorrhages of vocal folds. These beginning and reversible vascular changes, when early detected and discussed basing on etiological knowledge, may lead to more differentiated prognostic statements and adequate therapeutic decisions, e. g. phonosurgery, functional voice therapy, voice hygiene and voice rest. Vertical vascular changes, like vessel loops, occur primarily in laryngeal papilloma, pre-cancerous and cancerous changes of the vocal folds. Already in small cancerous lesions of the vocal folds the vascular architecture is completely destroyed. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Acute compartment syndrome caused by uncontrolled hypothyroidism.

    PubMed

    Modi, Anar; Amin, Hari; Salzman, Matthew; Morgan, Farah

    2017-06-01

    Acute compartment syndrome is increased tissue pressure exceeding perfusion pressure in a closed compartment resulting in nerve and muscle ischemia. Common precipitating causes are crush injuries, burns, substance abuse, osseous or vascular limb trauma. This is a case of 42year old female with history of hypothyroidism who presented to emergency room with acute onset of severe pain and swelling in right lower extremity. Physical examination was concerning for acute compartment syndrome of right leg which was confirmed by demonstration of elevated compartmental pressures. No precipitating causes were readily identified. Further laboratory testing revealed uncontrolled hypothyroidism. Management included emergent fasciotomy and initiating thyroid hormone replacement. This case represents a rare association between acute compartment syndrome and uncontrolled hypothyroidism. We also discuss the pathogenesis of compartment syndrome in hypothyroid patients and emphasize the importance of evaluating for less common causes, particularly in setting of non-traumatic compartment syndrome. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. The effect of sex counselling in the sexual activity of acute myocardial infarction patients after primary percutaneous coronary intervention.

    PubMed

    Xu, Feng; Ming, Qiang; Hou, Lei

    2015-08-01

    Primary percutaneous coronary intervention has improved the outcome of acute myocardial infarction (AMI) patients. Counsel-guided sex rehabilitation efficacy in acute myocardial infarction patients receiving percutaneous coronary intervention remains unknown. The aim of the study was to study counsel-guided sex rehabilitation efficacy in AMI patients receiving percutaneous coronary intervention. 240 AMI patients who received percutaneous coronary intervention were randomly divided into a control and a counselling group. Control group patients were given written sex rehabilitation instruction before discharge, while counselling group patients were given written instruction before discharge and monthly counselling with healthcare providers. Before discharge, the first evaluation was performed for frequency of and satisfaction with sexual activity before AMI. At one year of follow-up, the time of resuming, frequency of and satisfaction with sexual activity was evaluated. The main adverse event rates were also investigated. No significant differences in age, sex, smoking status, hypertension, diabetes, PVD (peripheral vascular disease), EF (ejection fraction) or GRACE (Global Registry of Acute Coronary Events) score were found between the groups. Both groups suffered reduced frequency of and satisfaction with sexual activity after AMI as compared with prior to presentation with AMI. However, compared with controls, the counselling group had higher scores for frequency of and satisfaction with sexual activity after AMI. The time to resume sexual activity after AMI in the counselling group was significantly shorter than was found for the control group.There were no significant differences between the groups for recurrent AMI, non-fatal stroke, admitting the patient for angina, all-cause death or adverse events. Intermittent discussions between healthcare providers and AMI patients improved resumption of sexual activity. Encouraging patients who received complete coronary

  7. [Cerebellar infarction in vascular teritorry of arteria cerebelli superior].

    PubMed

    Savić, Dejan; Savić, Ljiljana

    2010-01-01

    Cerebellar vascular diseases are focal cerebrovascular diseases in posterior circulation--vertebrobasilar system. The cerebellum is supplied by three main arteries arising from the vertebrobasilar system: arteria cerebelli inferior posterior, arteria cerebelli inferior anterior and arteria cerebelli superior. Cerebelar infarctions are rare but unpredictable disorders. The aim of this study was determination of main risk factors, clinical presentation and prognosis of the cerebellar infarctions in distal vascular teritorry of the arteria cerebelli superior. We evaluated 60 patients hospitalized after acute cerebellar infarction among other hospitalized patients in five year period. In 18 patients computerized tomography demonstrated infarction in distal vascular teritorry of the arteria cerebelli superior. All patients underwent clinical and other diagnostic investigations (computerized tomography, electrocardyography and standard blood tests) and were questioned by phone after finishing hospital treatment. Cerebellar infarcts in distal vascular teritorry of arteria cerebell superior was 30% of all cerebellar infarcts. The most frequent risk factor was hypertension (66.7%). Symptomatology and clinical signs were heterogenous but the most frequent were instability (77.8%), vertigo (72.2%) and vomiting (55.6%) followed by ataxia of the limbs (77.8%) and the body (61.1%), nystagmus (55.6%) and disarthria (33.3%) in clinical presentation. All patients had good recovery in hospital and one year afterwards. Infarctions in distribution of arteria cerebelli superior are rare and have multiple risk factors and various clinical features in majority of other studies as in this one. Mass effects are present in several studies but none in this one which reflects contraversions present in other published investigations. Cerebellar infarctions in vascular teritorry of arteria cerebelli superior have multiple risk factors, mostly heterogenous clinical presentations with

  8. Change in Growth Differentiation Factor 15, but Not C-Reactive Protein, Independently Predicts Major Cardiac Events in Patients with Non-ST Elevation Acute Coronary Syndrome

    PubMed Central

    Hernandez-Baldomero, Idaira F.; Bosa-Ojeda, Francisco

    2014-01-01

    Among the numerous emerging biomarkers, high-sensitivity C-reactive protein (hsCRP) and growth-differentiation factor-15 (GDF-15) have received widespread interest, with their potential role as predictors of cardiovascular risk. The concentrations of inflammatory biomarkers, however, are influenced, among others, by physiological variations, which are the natural, within-individual variation occurring over time. The aims of our study are: (a) to describe the changes in hsCRP and GDF-15 levels over a period of time and after an episode of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and (b) to examine whether the rate of change in hsCRP and GDF-15 after the acute event is associated with long-term major cardiovascular adverse events (MACE). Two hundred and Fifty five NSTE-ACS patients were included in the study. We measured hsCRP and GDF-15 concentrations, at admission and again 36 months after admission (end of the follow-up period). The present study shows that the change of hsCRP levels, measured after 36 months, does not predict MACE in NSTEACS-patients. However, the level of GDF-15 measured, after 36 months, was a stronger predictor of MACE, in comparison to the acute unstable phase. PMID:24839357

  9. The frequency and severity of extinction after stroke affecting different vascular territories.

    PubMed

    Chechlacz, Magdalena; Rotshtein, Pia; Demeyere, Nele; Bickerton, Wai-Ling; Humphreys, Glyn W

    2014-02-01

    We examined the frequency and severity of visual versus tactile extinction based on data from a large group of sub-acute patients (n=454) with strokes affecting different vascular territories. After right hemisphere damage visual and tactile extinction were equally common. However, after left hemisphere damage tactile extinction was more common than visual. The frequency of extinction was significantly higher in patients with right compared to left hemisphere damage in both visual and tactile modalities but this held only for strokes affecting the MCA and PCA territories and not for strokes affecting other vascular territories. Furthermore, the severity of extinction did not differ as a function of either the stimulus modality (visual versus tactile), the affected hemisphere (left versus right) or the stroke territory (MCA, PCA or other vascular territories). We conclude that the frequency but not severity of extinction in both modalities relates to the side of damage (i.e. left versus right hemisphere) and the vascular territories affected by the stroke, and that left hemisphere dominance for motor control may link to the greater incidence of tactile than visual extinction after left hemisphere stroke. We discuss the implications of our findings for understanding hemispheric lateralization within visuospatial attention networks. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Lifestyle and metabolic approaches to maximizing erectile and vascular health.

    PubMed

    Meldrum, D R; Gambone, J C; Morris, M A; Esposito, K; Giugliano, D; Ignarro, L J

    2012-01-01

    Oxidative stress and inflammation, which disrupt nitric oxide (NO) production directly or by causing resistance to insulin, are central determinants of vascular diseases including ED. Decreased vascular NO has been linked to abdominal obesity, smoking and high intakes of fat and sugar, which all cause oxidative stress. Men with ED have decreased vascular NO and circulating and cellular antioxidants. Oxidative stress and inflammatory markers are increased in men with ED, and all increase with age. Exercise increases vascular NO, and more frequent erections are correlated with decreased ED, both in part due to stimulation of endothelial NO production by shear stress. Exercise and weight loss increase insulin sensitivity and endothelial NO production. Potent antioxidants or high doses of weaker antioxidants increase vascular NO and improve vascular and erectile function. Antioxidants may be particularly important in men with ED who smoke, are obese or have diabetes. Omega-3 fatty acids reduce inflammatory markers, decrease cardiac death and increase endothelial NO production, and are therefore critical for men with ED who are under age 60 years, and/or have diabetes, hypertension or coronary artery disease, who are at increased risk of serious or even fatal cardiac events. Phosphodiesterase inhibitors have recently been shown to improve antioxidant status and NO production and allow more frequent and sustained penile exercise. Some angiotensin II receptor blockers decrease oxidative stress and improve vascular and erectile function and are therefore preferred choices for lowering blood pressure in men with ED. Lifestyle modifications, including physical and penile-specific exercise, weight loss, omega-3 and folic acid supplements, reduced intakes of fat and sugar, and improved antioxidant status through diet and/or supplements should be integrated into any comprehensive approach to maximizing erectile function, resulting in greater overall success and patient

  11. Modulation of vascular function by diet and exercise.

    PubMed

    Jennings, G L; Chin-Dusting, J P; Kingwell, B A; Dart, A M; Cameron, J; Esler, M; Lewis, T V

    1997-01-01

    Clinical research is conducted in free living individuals who are always subject to the influences on vascular function and the major cardiovascular regulators of their lifestyle. The purpose of this paper is to review some lifestyle influences on cardiovascular function, particularly the sympathetic nervous system and endothelially mediated vasodilatation. There are highly differentiated sympathetic responses to feeding, and to acute exercise. Over a longer period obesity has a typical pattern of sympathetic activity. Reduced dietary salt intake elicits profound localised increases in sympathetic activity to the kidney. Marine oil supplementation attenuates the sympathetic responses to psychological stress and improves endothelially mediated vasodilatation in hypercholesterolaemics. Exercise training reduced total noradrenaline spillover, the major beds affected being the renal and skeletal muscle. These examples illustrate the dynamic nature of vascular dilatation and that, like the sympathetic nervous system, it is modulated by short, medium and long term influences. In both cases there is regulation both at a local and systemic level. Habitual, and recent, lifestyle can exert important cardiovascular effects which must be taken into account in clinical and epidemiological research.

  12. Management strategies for neoplastic and vascular brain lesions presenting during pregnancy: A series of 29 patients

    PubMed Central

    Pereira, Celestino Esteves; Lynch, Jose Carlos

    2017-01-01

    Background: The occurrence of a brain tumor or intracranial vascular lesion during pregnancy is a rare event, but when it happens, it jeopardizes the lives of both the mother and infant. It also creates challenges of a neurosurgical, obstetric, and ethical nature. A multidisciplinary approach should be used for their care. Methods: Between 1986 and 2015, 12 pregnant women diagnosed with brain tumors and 17 women with intracranial vascular lesion underwent treatment at the Neurosurgery Department of the Servidores do Estado Hospital and Rede D’Or/São Luis. The Neurosurgery Department teamed up with Obstetrics Anesthesiology Departments in establishing the procedures. The patients’ records, surgical descriptions, imaging studies, and histopathological material were reviewed. Results: Among 12 patients presenting with brain tumors, there were neither operative mortality nor fetal deaths. Among the vascular lesions, aneurysm rupture was responsible for bleeding in 6 instances. Arteriovenous malformation was diagnosed in 7 patients. In this subgroup, the maternal and fetal mortality rates were 11.7% and 23.7%, respectively. Conclusions: We can assert that the association between a brain tumor and vascular lesions with pregnancy is a very unusual event, which jeopardizes both the lives of the mother and infant. It remains incompletely characterized due to the rare nature of these potentially devastating events. Knowing the exact mechanism responsible for the interaction of pregnancy and with these lesions will improve the treatment of these patients. PMID:28303207

  13. Vascular Cognitive Impairment.

    PubMed

    Dichgans, Martin; Leys, Didier

    2017-02-03

    Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts. © 2017 American Heart Association, Inc.

  14. Pulmonary hypertensive crisis following ethanol sclerotherapy for a complex vascular malformation.

    PubMed

    Cordero-Schmidt, G; Wallenstein, M B; Ozen, M; Shah, N A; Jackson, E; Hovsepian, D M; Palma, J P

    2014-09-01

    Anhydrous ethanol is a commonly used sclerotic agent for treating vascular malformations. We describe the case of a full-term 15-day-old female with a complex venolymphatic malformation involving the face and orbit. During treatment of the lesion with ethanol sclerotherapy, she suffered acute pulmonary hypertensive crisis. We discuss the pathophysiology of pulmonary hypertension related to ethanol sclerotherapy, and propose that hemolysis plays a significant role. Recommendations for evaluation, monitoring and management of this complication are also discussed.

  15. Protective role of sulphoraphane against vascular complications in diabetes.

    PubMed

    Yamagishi, Sho-Ichi; Matsui, Takanori

    2016-10-01

    Context Diabetes is a global health challenge. Although large prospective clinical trials have shown that intensive control of blood glucose or blood pressure reduces the risk for development and progression of vascular complications in diabetes, a substantial number of diabetic patients still experience renal failure and cardiovascular events, which could account for disabilities and high mortality rate in these subjects. Objective Sulphoraphane is a naturally occurring isothiocyanate found in widely consumed cruciferous vegetables, such as broccoli, cabbage and Brussels sprouts, and an inducer of phase II antioxidant and detoxification enzymes with anticancer properties. We reviewed here the protective role of sulphoraphane against diabetic vascular complications. Methods In this review, literature searches were undertaken in Medline and in CrossRef. Non-English language articles were excluded. Keywords [sulphoraphane and (diabetes, diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, diabetic complications, vascular, cardiomyocytes, heart or glycation)] have been used to select the articles. Results There is accumulating evidence that sulphoraphane exerts beneficial effects on vascular damage in both cell culture and diabetic animal models via antioxidative properties. Furthermore, we have recently found that sulphoraphane inhibits in vitro formation of advanced glycation end products (AGEs), suppresses the AGE-induced inflammatory reactions in rat aorta by reducing receptor for AGEs (RAGE) expression and decreases serum levels of AGEs in humans. Conclusion These findings suggest that blockade of oxidative stress and/or the AGE-RAGE axis by sulphoraphane may be a novel therapeutic strategy for preventing vascular complications in diabetes.

  16. Vascular trauma: selected historical reflections from the western world.

    PubMed

    Rich, Norman-M; McKay, Patricia-L; Welling, David-R; Rasmussen, Todd-E

    2011-04-01

    In the spirit of international exchanges of knowledge with colleagues from all over the world, who are interested in the care and treatment of vascular trauma, we offer selected historical reflections from the western world on vascular trauma. Whereas there are a number of key individuals and a variety of events that are important to us in our writing, we know essentially nothing about what is written by other cultures and, particularly, the Chinese. It is well recognized around the world that Chinese surgeons are among the first to be highly successful in re-plantation of severed extremities, repairing both injured arteries and veins. Also, we recognize that there are contributions in other parts of the world, which are not well known to us collectively. Contributions from the Arabic speaking part of the world come to mind because there is periodic brief reference. We offer our perspective hoping that there will be one or more Chinese surgeons who will offer us the benefit of sharing their perspective on important historical contributions to the managing of vascular trauma outside of the western world, and, particularly, the English speaking literature. Once again, we encourage our colleagues in the Arabic speaking world to provide us with their perspective of the development and management of vascular trauma.

  17. Branding of vascular surgery.

    PubMed

    Perler, Bruce A

    2008-03-01

    The Society for Vascular Surgery surveyed primary care physicians (PCPs) to understand how PCPs make referral decisions for their patients with peripheral vascular disease. Responses were received from 250 PCPs in 44 states. More than 80% of the respondents characterized their experiences with vascular surgeons as positive or very positive. PCPs perceive that vascular surgeons perform "invasive" procedures and refer patients with the most severe vascular disease to vascular surgeons but were more than twice as likely to refer patients to cardiologists, believing they are better able to perform minimally invasive procedures. Nevertheless, PCPs are receptive to the notion of increasing referrals to vascular surgeons. A successful branding campaign will require considerable education of referring physicians about the totality of traditional vascular and endovascular care increasingly provided by the contemporary vascular surgical practice and will be most effective at the local grassroots level.

  18. Vascular Aging: Lessons From Pediatric Hypertension.

    PubMed

    Litwin, Mieczyslaw; Feber, Janusz; Ruzicka, Marcel

    2016-05-01

    Hypertension (HTN) in children is associated with early vascular aging (EVA) and underlying immunologic-metabolic abnormalities and accelerated biological maturation. Morphologic and functional vascular changes underlying EVA and HTN in children resemble those seen in the elderly including but not limited to an increase in intima-media thickness (IMT) and arterial stiffness and endothelial dysfunction. Although progeria syndrome leading to EVA and the development of clinically manifested cardiovascular (CV) disease in the second decade of life is a rare hereditary disorder, primary HTN, which is also associated with EVA, is much more common (reported in up to 10% in adolescents). EVA associated with HTN in children leads to the premature development of target organ injury in childhood and CV events in early adulthood. Limited evidence from prospective observational studies in children and adolescents indicates that early lifestyle measures (low salt/low sugar intake and exercise) or pharmacologic treatment of HTN, or both, partially reverses morphologic and functional changes underlying EVA such as an increase in carotid IMT and pulse wave velocity, a decrease in flow-mediated dilation of the brachial artery, and an increase in oxidative stress and visceral fat. Future mechanistic and therapeutic clinical trials are desirable to assess the mechanisms and treatment strategies of EVA in the context of HTN in children and their effect on CV events in early adulthood. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  19. Co-administration of pentoxifylline and thiopental causes death by acute pulmonary oedema in rats

    PubMed Central

    Pereda, J; Gómez-Cambronero, L; Alberola, A; Fabregat, G; Cerdá, M; Escobar, J; Sabater, L; García-de-la-Asuneión, J; Viña, J; Sastre, J

    2006-01-01

    Background and purpose: Pentoxifylline exhibits rheological properties that improve microvascular flow and it is widely used in vascular perfusion disorders. It also exhibits marked anti-inflammatory properties by inhibiting tumour necrosis factor α production. Thiopental is one of the most widely used drugs for rapid induction of anaesthesia. During experimental studies on the treatment of acute pancreatitis, we observed that when pentoxifylline was administered after anaesthesia with thiopental, most of the rats exhibited dyspnea, signs of pulmonary oedema and died. The aim of the work described here was to investigate the cause of the unexpected toxic effect of the combined treatment with thiopental and pentoxifylline. Experimental approach: Pulmonary vascular permeability and arterial blood gases were measured, and a histological analysis was performed. The possible role of haemodynamic changes in the formation of pulmonary oedema was also assessed. Key results: Co-administration of pentoxifylline and thiopental increased pulmonary vascular permeability and markedly decreased arterial pO2, with one third of rats suffering from hypoxemia. This combined treatment caused death by acute pulmonary oedema in 27% of normal rats and aggravated the respiratory insufficiency associated with acute pancreatitis in which the mortality rate increased to 60%. This pulmonary oedema was not mediated by cardiac failure or by pulmonary hypertension. Conclusions and Implications: Co-administration of pharmacological doses of pentoxifylline and thiopental caused pulmonary oedema and death in rats. Consequently, pentoxifylline should not be administered when anaesthesia is induced with thiopental to avoid any possible risk of acute pulmonary oedema and death in humans. PMID:16953192

  20. Vascular Effects of Phytoestrogens and Alternative Menopausal Hormone Therapy in Cardiovascular Disease

    PubMed Central

    Gencel, Vahide B.; Benjamin, Mina M.; Bahou, Shafik N.; Khalil, Raouf A.

    2011-01-01

    Phytoestrogens are estrogenic compounds of plant origin classified into different groups including isoflavones, lignans, coumestans and stilbenes. Isoflavones such as genistein and daidzein are the most studied and most potent phytoestrogens, and are found mainly in soy based foods. The effects of phytoestrogens are partly mediated via estrogen receptors (ERs): ERα, ERβ and possibly GPER. The interaction of phytoestrogens with ERs is thought to induce both genomic and non-genomic effects in many tissues including the vasculature. Some phytoestrogens such as genistein have additional non-ER-mediated effects involving signaling pathways such as tyrosine kinase. Experimental studies have shown beneficial effects of phytoestrogens on endothelial cells, vascular smooth muscle, and extracellular matrix. Phytoestrogens may also affect other pathophysiologic vascular processes such as lipid profile, angiogenesis, inflammation, tissue damage by reactive oxygen species, and these effects could delay the progression of atherosclerosis. As recent clinical trials showed no vascular benefits or even increased risk of cardiovascular disease (CVD) and CV events with conventional menopausal hormone therapy (MHT), phytoestrogens are being considered as alternatives to pharmacologic MHT. Epidemiological studies in the Far East population suggest that dietary intake of phytoestrogens may contribute to the decreased incidence of postmenopausal CVD and thromboembolic events. Also, the WHO-CARDIAC study supported that consumption of high soybean diet is associated with lower mortalities from coronary artery disease. However, as with estrogen, there has been some discrepancy between the experimental studies demonstrating the vascular benefits of phytoestrogens and the data from clinical trials. This is likely because the phytoestrogens clinical trials have been limited in many aspects including the number of participants enrolled, the clinical end points investigated, and the lack of

  1. Risks from Solar Particle Events for Long Duration Space Missions Outside Low Earth Orbit

    NASA Technical Reports Server (NTRS)

    Over, S.; Myers, J.; Ford, J.

    2016-01-01

    The Integrated Medical Model (IMM) simulates the medical occurrences and mission outcomes for various mission profiles using probabilistic risk assessment techniques. As part of the work with the Integrated Medical Model (IMM), this project focuses on radiation risks from acute events during extended human missions outside low Earth orbit (LEO). Of primary importance in acute risk assessment are solar particle events (SPEs), which are low probability, high consequence events that could adversely affect mission outcomes through acute radiation damage to astronauts. SPEs can be further classified into coronal mass ejections (CMEs) and solar flares/impulsive events (Fig. 1). CMEs are an eruption of solar material and have shock enhancements that contribute to make these types of events higher in total fluence than impulsive events.

  2. The oxidized low-density lipoprotein receptor mediates vascular effects of inhaled vehicle emissions

    EPA Science Inventory

    Rationale: To determine vascular signaling pathways involved in air pollution (vehicular engine emission) exposure -induced exacerbation of atherosclerosis, associated with onset of clinical cardiovascular events. Objective: To elucidate the role of oxidized LDL (oxLDL) and its ...

  3. HLA-DRB1*04/*13 alleles are associated with vascular disease and antiphospholipid antibodies in systemic lupus erythematosus.

    PubMed

    Lundström, Emeli; Gustafsson, Johanna T; Jönsen, Andreas; Leonard, Dag; Zickert, Agneta; Elvin, Kerstin; Sturfelt, Gunnar; Nordmark, Gunnel; Bengtsson, Anders A; Sundin, Ulf; Källberg, Henrik; Sandling, Johanna K; Syvänen, Ann-Christine; Klareskog, Lars; Gunnarsson, Iva; Rönnblom, Lars; Padyukov, Leonid; Svenungsson, Elisabet

    2013-06-01

    Vascular disease is common in systemic lupus erythematosus (SLE) and patients with antiphospholipid antibodies (aPL) are at high risk to develop arterial and venous thrombosis. Since HLA class II genotypes have been linked to the presence of pro-thrombotic aPL, we investigated the relationship between HLA-DRB1 alleles, aPL and vascular events in SLE patients. 665 SLE patients of Caucasian origin and 1403 controls were included. Previous manifestations of ischaemic heart disease, ischaemic cerebrovascular disease (ICVD) and venous thromboembolism (together referred to as any vascular events (AVE)) were tabulated. aPL were measured with ELISA. Two-digit HLA-DRB1 typing was performed by sequence-specific primer-PCR. HLA-DRB1*04 was more frequent among SLE patients with ICVD compared to unaffected patients. This association remained after adjustment for known traditional cardiovascular risk factors. HLA-DRB1*13 was associated with AVE. All measured specificities of aPL-cardiolipin IgG and IgM, β2-glycoprotein-1 IgG, prothrombin (PT) IgG and a positive lupus anticoagulant test were associated with HLA-DRB1*04-while HLA-DRB1*13 was associated with IgG antibodies (β2-glycoprotein-1, cardiolipin and PT). In patients with the combined risk alleles, HLA-DRB1*04/*13, there was a significant additive interaction for the outcomes AVE and ICVD. The HLA-DRB1*04 and HLA-DRB1*13 alleles are associated with vascular events and an aPL positive immune-phenotype in SLE. Results demonstrate that a subset of SLE patients is genetically disposed to vascular vulnerability.

  4. China Patient-centered Evaluative Assessment of Cardiac Events Prospective Study of Acute Myocardial Infarction: Study Design

    PubMed Central

    Li, Jing; Dreyer, Rachel P; Li, Xi; Du, Xue; Downing, Nicholas S; Li, Li; Zhang, Hai-Bo; Feng, Fang; Guan, Wen-Chi; Xu, Xiao; Li, Shu-Xia; Lin, Zhen-Qiu; Masoudi, Frederick A; Spertus, John A; Krumholz, Harlan M; Jiang, Li-Xin

    2016-01-01

    Background: Despite the rapid growth in the incidence of acute myocardial infarction (AMI) in China, there is limited information about patients’ experiences after AMI hospitalization, especially on long-term adverse events and patient-reported outcomes (PROs). Methods: The China Patient-centered Evaluative Assessment of Cardiac Events (PEACE)-Prospective AMI Study will enroll 4000 consecutive AMI patients from 53 diverse hospitals across China and follow them longitudinally for 12 months to document their treatment, recovery, and outcomes. Details of patients’ medical history, treatment, and in-hospital outcomes are abstracted from medical charts. Comprehensive baseline interviews are being conducted to characterize patient demographics, risk factors, presentation, and healthcare utilization. As part of these interviews, validated instruments are administered to measure PROs, including quality of life, symptoms, mood, cognition, and sexual activity. Follow-up interviews, measuring PROs, medication adherence, risk factor control, and collecting hospitalization events are conducted at 1, 6, and 12 months after discharge. Supporting documents for potential outcomes are collected for adjudication by clinicians at the National Coordinating Center. Blood and urine samples are also obtained at baseline, 1- and 12-month follow-up. In addition, we are conducting a survey of participating hospitals to characterize their organizational characteristics. Conclusion: The China PEACE-Prospective AMI study will be uniquely positioned to generate new information regarding patient's experiences and outcomes after AMI in China and serve as a foundation for quality improvement activities. PMID:26712436

  5. Neutrophil subsets and their gene signature associate with vascular inflammation and coronary atherosclerosis in lupus

    PubMed Central

    Carlucci, Philip M.; Purmalek, Monica M.; Dey, Amit K.; Temesgen-Oyelakin, Yenealem; Sakhardande, Simantini; Joshi, Aditya A.; Lerman, Joseph B.; Fike, Alice; Davis, Michael; Chung, Jonathan H.; Playford, Martin P.; Naqi, Mohammad; Mistry, Pragnesh; Gutierrez-Cruz, Gustavo; Dell’Orso, Stefania; Naz, Faiza; Salahuddin, Taufiq; Natarajan, Balaji; Tsai, Wanxia L.; Gupta, Sarthak; Grayson, Peter; Chen, Marcus Y.; Sun, Hong-Wei; Hasni, Sarfaraz; Mehta, Nehal N.

    2018-01-01

    BACKGROUND. Systemic lupus erythematosus (SLE) is associated with enhanced risk of atherosclerotic cardiovascular disease not explained by Framingham risk score (FRS). Immune dysregulation associated to a distinct subset of lupus proinflammatory neutrophils (low density granulocytes; LDGs) may play key roles in conferring enhanced CV risk. This study assessed if lupus LDGs are associated with in vivo vascular dysfunction and inflammation and coronary plaque. METHODS. SLE subjects and healthy controls underwent multimodal phenotyping of vascular disease by quantifying vascular inflammation (18F-fluorodeoxyglucose–PET/CT [18F-FDG–PET/CT]), arterial dysfunction (EndoPAT and cardio-ankle vascular index), and coronary plaque burden (coronary CT angiography). LDGs were quantified by flow cytometry. Cholesterol efflux capacity was measured in high-density lipoprotein–exposed (HDL-exposed) radioactively labeled cell lines. Whole blood RNA sequencing was performed to assess associations between transcriptomic profiles and vascular phenotype. RESULTS. Vascular inflammation, arterial stiffness, and noncalcified plaque burden (NCB) were increased in SLE compared with controls even after adjustment for traditional risk factors. In SLE, NCB directly associated with LDGs and associated negatively with cholesterol efflux capacity in fully adjusted models. A neutrophil gene signature reflective of the most upregulated genes in lupus LDGs associated with vascular inflammation and NCB. CONCLUSION. Individuals with SLE demonstrate vascular inflammation, arterial dysfunction, and NCB, which may explain the higher reported risk for acute coronary syndromes. The association of LDGs and neutrophil genes with vascular disease supports the hypothesis that distinct neutrophil subsets contribute to vascular damage and unstable coronary plaque in SLE. Results also support previous observations that neutrophils may disrupt HDL function and thereby promote atherogenesis. TRIAL REGISTRATION

  6. Scanning electron microscopy observation of vascularization around hydroxyapatite using vascular corrosion casts.

    PubMed

    Chang, C S; Su, C Y; Lin, T C

    1999-01-01

    An intimate relationship exists between the regenerative response of the vascular and osseous elements following hydroxyapatite (HA) implantation. In order to fully comprehend the 3-dimensional vascular architecture around HA, dense HA particles were implanted into the tibiae of dogs. Following healing periods of 2 weeks, 1 month, and 3 months, the tibiae were prepared by the corrosion cast technique. Under scanning electron microscopy (SEM) observation, the characteristic vascular morphology of the HA-implanted cavity was successfully demonstrated. The initial vascularization began in the form of loose sinusoidal capillaries. Many sinusoids formed a complex network by anastomosing with each other. The newly formed vessels extended centripetally from the peripheral cavity wall and from the periosteal surface. Under greater magnification, the tapered vascular sprouting was shown to project into the space that was previously occupied by an HA particle. The presence of vascular sprouting is clearly an important indicator of angiogenesis. Increasing vascularization was demonstrated with time. The presence of vessels in the Haversian's canal indicated the more established vascularization. Almost full vascularization of the HA-implanted cavity was seen 3 months after implantation. The vascular organizational layout of the cavity was also clearly shown in the fractured transverse-sectioned sample. In the control without HA implantation, the central region of the cavity showed a hollow pattern in the initial stage. The vascularization looked like it was collapsing and not fully filling the cavity. However, remarkable differences of the final vascular pattern could not be found between the study and control group after 3-month implantation. The study provides the time-lapsed 3-dimensional vascular changes of the HA-implanted cavity, as well as the value of the corrosion cast technique in examining the bony circulation. Copyright 1999 John Wiley & Sons, Inc.

  7. Vascular responses to radiotherapy and androgen-deprivation therapy in experimental prostate cancer

    PubMed Central

    2012-01-01

    Background Radiotherapy (RT) and androgen-deprivation therapy (ADT) are standard treatments for advanced prostate cancer (PC). Tumor vascularization is recognized as an important physiological feature likely to impact on both RT and ADT response, and this study therefore aimed to characterize the vascular responses to RT and ADT in experimental PC. Methods Using mice implanted with CWR22 PC xenografts, vascular responses to RT and ADT by castration were visualized in vivo by DCE MRI, before contrast-enhancement curves were analyzed both semi-quantitatively and by pharmacokinetic modeling. Extracted image parameters were correlated to the results from ex vivo quantitative fluorescent immunohistochemical analysis (qIHC) of tumor vascularization (9 F1), perfusion (Hoechst 33342), and hypoxia (pimonidazole), performed on tissue sections made from tumors excised directly after DCE MRI. Results Compared to untreated (Ctrl) tumors, an improved and highly functional vascularization was detected in androgen-deprived (AD) tumors, reflected by increases in DCE MRI parameters and by increased number of vessels (VN), vessel density ( VD), and vessel area fraction ( VF) from qIHC. Although total hypoxic fractions ( HF) did not change, estimated acute hypoxia scores ( AHS) – the proportion of hypoxia staining within 50 μm from perfusion staining – were increased in AD tumors compared to in Ctrl tumors. Five to six months after ADT renewed castration-resistant (CR) tumor growth appeared with an even further enhanced tumor vascularization. Compared to the large vascular changes induced by ADT, RT induced minor vascular changes. Correlating DCE MRI and qIHC parameters unveiled the semi-quantitative parameters area under curve ( AUC) from initial time-points to strongly correlate with VD and VF, whereas estimation of vessel size ( VS) by DCE MRI required pharmacokinetic modeling. HF was not correlated to any DCE MRI parameter, however, AHS may be estimated after

  8. Aging, not age-associated inflammation, determines blood pressure and endothelial responses to acute inflammation.

    PubMed

    Lane-Cordova, Abbi D; Ranadive, Sushant M; Kappus, Rebecca M; Cook, Marc D; Phillips, Shane A; Woods, Jeffrey A; Wilund, Kenneth R; Baynard, Tracy; Fernhall, Bo

    2016-12-01

    Aging is characterized by a state of chronic, low-grade inflammation that impairs vascular function. Acute inflammation causes additional decrements in vascular function, but these responses are not uniform in older compared with younger adults. We sought to determine if older adults with low levels of baseline inflammation respond to acute inflammation in a manner similar to younger adults. We hypothesized age-related differences in the vascular responses to acute inflammation, but that older adults with low baseline inflammation would respond similarly to younger adults. Inflammation was induced with an influenza vaccine in 96 participants [older = 67 total, 38 with baseline C-reactive protein (CRP) > 1.5 mg/l and 29 with CRP < 1.5 mg/l; younger = 29]; serum inflammatory markers IL-6 and CRP, blood pressure and flow-mediated dilation (FMD) were measured 24 and 48 h later. Younger adults increased IL-6 and CRP more than the collective older adult group and increased pulse pressure, whereas older adults decreased SBP and reduced pulse pressure. The entire cohort decreased FMD from 11.3 ± 0.8 to 8.3 ± 0.7 to 8.7 ± 0.7% in younger and from 5.8 ± 0.3 to 5.0 ± 0.4 to 4.7 ± 0.4% in older adults, P less than 0.05 for main effect. Older adult groups with differing baseline CRP had the same IL-6, blood pressure, and FMD response to acute inflammation, P less than 0.05 for all interactions, but the low-CRP group increased CRP at 24 and 48 h (from 0.5 ± 0.1 to 1.4 ± 0.2 to 1.7 ± 0.3 mg/l), whereas the high-CRP group did not (from 4.8 ± 0.5 to 5.4 ± 0.5 to 5.4 ± 0.6 mg/l), P less than 0.001 for interaction. Aging, not age-related chronic, low-grade inflammation, determines the vascular responses to acute inflammation.

  9. Vascular Permeability and Remodelling Coincide with Inflammatory and Reparative Processes after Joint Bleeding in Factor VIII-Deficient Mice.

    PubMed

    Cooke, Esther J; Zhou, Jenny Y; Wyseure, Tine; Joshi, Shweta; Bhat, Vikas; Durden, Donald L; Mosnier, Laurent O; Drygalski, Annette von

    2018-06-01

    Vascular remodelling is a prominent feature of haemophilic arthropathy (HA) that may underlie re-bleeding, yet the nature of vascular changes and underlying mechanisms remain largely unknown. Here, we aimed to characterize synovial vascular remodelling and vessel integrity after haemarthrosis, as well as temporal changes in inflammatory and tissue-reparative pathways. Thirty acutely painful joints in patients with haemophilia (PWH) were imaged by musculoskeletal ultrasound with Power Doppler (MSKUS/PD) to detect vascular abnormalities and bloody effusions. Nineteen out of 30 painful joint episodes in PWH were associated with haemarthrosis, and abnormal vascular perfusion was unique to bleeding joints. A model of induced haemarthrosis in factor VIII (FVIII)-deficient mice was used for histological assessment of vascular remodelling (α-smooth muscle actin [αSMA] expression), and monitoring of in vivo vascular perfusion and permeability by MSKUS/PD and albumin extravasation, respectively. Inflammatory (M1) and reparative (M2) macrophage markers were quantified in murine synovium over a 10-week time course by real-time polymerase chain reaction. The abnormal vascular perfusion observed in PWH was recapitulated in FVIII-deficient mice after induced haemarthrosis. Neovascularization and increased vessel permeability were apparent 2 weeks post-bleed in FVIII-deficient mice, after a transient elevation of inflammatory macrophage M1 markers. These vascular changes subsided by week 4, while vascular remodelling, evidenced by architectural changes and pronounced αSMA expression, persisted alongside a reparative macrophage M2 response. In conclusion, haemarthrosis leads to transient inflammation coupled with neovascularization and associated vascular permeability, while subsequent tissue repair mechanisms coincide with vascular remodelling. Together, these vascular changes may promote re-bleeding and HA progression. Schattauer GmbH Stuttgart.

  10. Exercise capacity and muscle strength and risk of vascular disease and arrhythmia in 1.1 million young Swedish men: cohort study.

    PubMed

    Andersen, Kasper; Rasmussen, Finn; Held, Claes; Neovius, Martin; Tynelius, Per; Sundström, Johan

    2015-09-16

    To investigate the associations of exercise capacity and muscle strength in late adolescence with risk of vascular disease and arrhythmia. Cohort study. General population in Sweden. 1.1 million men who participated in mandatory military conscription between 1 August 1972 and 31 December 1995, at a median age of 18.2 years. Participants were followed until 31 December 2010. Associations between exercise capacity and muscle strength with risk of vascular disease and subgroups (ischaemic heart disease, heart failure, stroke, and cardiovascular death) and risk of arrhythmia and subgroups (atrial fibrillation or flutter, bradyarrhythmia, supraventricular tachycardia, and ventricular arrhythmia or sudden cardiac death). Maximum exercise capacity was estimated by the ergometer bicycle test, and muscle strength was measured as handgrip strength by a hand dynamometer. High exercise capacity or muscle strength was deemed as above the median level. During a median follow-up of 26.3 years, 26 088 vascular disease events and 17 312 arrhythmia events were recorded. Exercise capacity was inversely associated with risk of vascular disease and its subgroups. Muscle strength was also inversely associated with vascular disease risk, driven by associations of higher muscle strength with lower risk of heart failure and cardiovascular death. Exercise capacity had a U shaped association with risk of arrhythmia, driven by a direct association with risk of atrial fibrillation and a U shaped association with bradyarrhythmia. Higher muscle strength was associated with lower risk of arrhythmia (specifically, lower risk of bradyarrhythmia and ventricular arrhythmia). The combination of high exercise capacity and high muscle strength was associated with a hazard ratio of 0.67 (95% confidence interval 0.65 to 0.70) for vascular events and 0.92 (0.88 to 0.97) for arrhythmia compared with the combination of low exercise capacity and low muscle strength. Exercise capacity and muscle strength

  11. Measurements of pulmonary vascular permeability with PET and gallium-68 transferrin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mintun, M.A.; Dennis, D.R.; Welch, M.J.

    1987-11-01

    We quantified pulmonary vascular permeability with positron emission tomography (PET) and gallium-68-(/sup 68/Ga) labeled transferrin. Six dogs with oleic acid-induced lung injury confined to the left lower lobe, two normal human volunteers, and two patients with the adult respiratory distress syndrome (ARDS) were evaluated. Lung tissue-activity measurements were obtained from sequential 1-5 min PET scans collected over 60 min, after in vivo labeling of transferrin through intravenous administration of (/sup 68/Ga)citrate. Blood-activity measurements were measured from simultaneously obtained peripheral blood samples. A forward rate constant describing the movement of transferrin from pulmonary vascular to extravascular compartments, the pulmonary transcapillary escapemore » rate (PTCER), was then calculated from these data using a two-compartment model. In dogs, PTCER was 49 +/- 18 in normal lung tissue and 485 +/- 114 10(-4) min-1 in injured lung. A repeat study in these dogs 4 hr later showed no significant change. Values in the human subjects showed similarly marked differences between normal and abnormal lung tissue. We conclude that PET will be a useful method of evaluating vascular permeability changes after acute lung injury.« less

  12. Application of a Novel Murine Ear Vein Model to Evaluate the Effects of a Vascular Radioprotectant on Radiation-Induced Vascular Permeability and Leukocyte Adhesion.

    PubMed

    Ashcraft, Kathleen A; Choudhury, Kingshuk Roy; Birer, Sam R; Hendargo, Hansford C; Patel, Pranalee; Eichenbaum, Gary; Dewhirst, Mark W

    2018-04-19

    Vascular injury after radiation exposure contributes to multiple types of tissue injury through a cascade of events. Some of the earliest consequences of radiation damage include increased vascular permeability and promotion of inflammation, which is partially manifested by increased leukocyte-endothelial (L/E) interactions. We describe herein a novel intravital imaging method to evaluate L/E interactions, as a function of shear stress, and vascular permeability at multiple time points after local irradiation to the ear. This model permitted analysis of quiescent vasculature that was not perturbed by any surgical manipulation prior to imaging. To evaluate the effects of radiation on vascular integrity, fluorescent dextran was injected intravenously and its extravasation in the extravascular space surrounding the ear vasculature was measured at days 3 and 7 after 6 Gy irradiation. The vascular permeability rate increased approximately twofold at both days 3 and 7 postirradiation ( P < 0.05). Leukocyte rolling, which is indicative of L/E interactions, was significantly increased in mice at 24 h postirradiation compared to that of nonirradiated mice. To assess our model, as a means for assessing vascular radioprotectants, we treated additional cohorts of mice with a thrombopoietin mimetic, TPOm (RWJ-800088). In addition to stimulating platelet formation, thrombopoietin can protect vasculature after several forms of injury. Thus, we hypothesized that TPOm would reduce vascular permeability and L/E adhesion after localized irradiation to the ear vasculature of mice. If TPOm reduced these consequences of radiation, it would validate the utility of our intravital imaging method. TPOm reduced radiation-induced vascular leakage to control levels at day 7. Furthermore, L/E cell interactions were also reduced in irradiated mice treated with TPOm, compared with mice receiving irradiation alone, particularly at high shear stress ( P = 0.03, Kruskal-Wallis). We conclude that the

  13. Vascular and Inflammatory Factors in the Pathophysiology of Blast-Induced Brain Injury

    PubMed Central

    Elder, Gregory A.; Gama Sosa, Miguel A.; De Gasperi, Rita; Stone, James Radford; Dickstein, Dara L.; Haghighi, Fatemeh; Hof, Patrick R.; Ahlers, Stephen T.

    2015-01-01

    Blast-related traumatic brain injury (TBI) has received much recent attention because of its frequency in the conflicts in Iraq and Afghanistan. This renewed interest has led to a rapid expansion of clinical and animal studies related to blast. In humans, high-level blast exposure is associated with a prominent hemorrhagic component. In animal models, blast exerts a variety of effects on the nervous system including vascular and inflammatory effects that can be seen with even low-level blast exposures which produce minimal or no neuronal pathology. Acutely, blast exposure in animals causes prominent vasospasm and decreased cerebral blood flow along with blood-brain barrier breakdown and increased vascular permeability. Besides direct effects on the central nervous system, evidence supports a role for a thoracically mediated effect of blast; whereby, pressure waves transmitted through the systemic circulation damage the brain. Chronically, a vascular pathology has been observed that is associated with alterations of the vascular extracellular matrix. Sustained microglial and astroglial reactions occur after blast exposure. Markers of a central and peripheral inflammatory response are found for sustained periods after blast injury and include elevation of inflammatory cytokines and other inflammatory mediators. At low levels of blast exposure, a microvascular pathology has been observed in the presence of an otherwise normal brain parenchyma, suggesting that the vasculature may be selectively vulnerable to blast injury. Chronic immune activation in brain following vascular injury may lead to neurobehavioral changes in the absence of direct neuronal pathology. Strategies aimed at preventing or reversing vascular damage or modulating the immune response may improve the chronic neuropsychiatric symptoms associated with blast-related TBI. PMID:25852632

  14. Cardiovascular Events Following Smoke-Free Legislations: An Updated Systematic Review and Meta-Analysis

    PubMed Central

    Jones, Miranda R.; Barnoya, Joaquin; Stranges, Saverio; Losonczy, Lia; Navas-Acien, Ana

    2014-01-01

    Background Legislations banning smoking in indoor public places and workplaces are being implemented worldwide to protect the population from secondhand smoke exposure. Several studies have reported reductions in hospitalizations for acute coronary events following the enactment of smoke-free laws. Objective We set out to conduct a systematic review and meta-analysis of epidemiologic studies examining how legislations that ban smoking in indoor public places impact the risk of acute coronary events. Methods We searched MEDLINE, EMBASE, and relevant bibliographies including previous systematic reviews for studies that evaluated changes in acute coronary events, following implementation of smoke-free legislations. Studies were identified through December 2013. We pooled relative risk (RR) estimates for acute coronary events comparing post- vs. pre-legislation using inverse-variance weighted random-effects models. Results Thirty-one studies providing estimates for 47 locations were included. The legislations were implemented between 1991 and 2010. Following the enactment of smoke-free legislations, there was a 12 % reduction in hospitalizations for acute coronary events (pooled RR: 0.88, 95 % CI: 0.85–0.90). Reductions were 14 % in locations that implemented comprehensive legislations compared to an 8 % reduction in locations that only had partial restrictions. In locations with reductions in smoking prevalence post-legislation above the mean (2.1 % reduction) there was a 14 % reduction in events compared to 10 % in locations below the mean. The RRs for acute coronary events associated with enacting smoke-free legislation were 0.87 vs. 0.89 in locations with smoking prevalence pre-legislation above and below the mean (23.1 %), and 0.87 vs. 0.89 in studies from the Americas vs. other regions. Conclusion The implementation of smoke-free legislations was related to reductions in acute coronary event hospitalizations in most populations evaluated. Benefits are greater

  15. Population-based study of blood biomarkers in prediction of sub-acute recurrent stroke

    PubMed Central

    Segal, Helen C; Burgess, Annette I; Poole, Debbie L; Mehta, Ziyah; Silver, Louise E; Rothwell, Peter M

    2017-01-01

    Background and purpose Risk of recurrent stroke is high in the first few weeks after TIA or stroke and clinic risk prediction tools have only limited accuracy, particularly after the hyper-acute phase. Previous studies of the predictive value of biomarkers have been small, been done in selected populations and have not concentrated on the acute phase or on intensively treated populations. We aimed to determine the predictive value of a panel of blood biomarkers in intensively treated patients early after TIA and stroke. Methods We studied 14 blood biomarkers related to inflammation, thrombosis, atherogenesis and cardiac or neuronal cell damage in early TIA or ischaemic stroke in a population-based study (Oxford Vascular Study). Biomarker levels were related to 90-day risk of recurrent stroke as Hazard Ratio (95%CI) per decile increase, adjusted for age and sex. Results Among 1292 eligible patients there were 53 recurrent ischaemic strokes within 90 days. There were moderate correlations (r>0.40; p<0001) between the inflammatory biomarkers and between the cell damage and thrombotic subsets. However, associations with risk of early recurrent stroke were weak, with significant associations limited to Interleukin-6 (HR=1.12, 1.01-1.24; p=0.035) and C-reactive protein (1.16, 1.02-1.30; p=0.019). When stratified by type of presenting event, P-selectin predicted stroke after TIA (1.31, 1.03-1.66; p=0.028) and C-reactive protein predicted stroke after stroke (1.16, 1.01-1.34; p=0.042). These associations remained after fully adjusting for other vascular risk factors. Conclusion In the largest study to date, we found very limited predictive utility for early recurrent stroke for a panel of inflammatory, thrombotic and cell damage biomarkers. PMID:25158774

  16. At the heart of the problem - A person-centred, developmental perspective on the link between alcohol consumption and cardio-vascular events.

    PubMed

    Lima Passos, Valéria; Klijn, Sven; van Zandvoort, Kevin; Abidi, Latifa; Lemmens, Paul

    2017-04-01

    The cardio-protective effect of alcohol has been the subject of a long-standing scientific controversy. Emerging evidence remains equivocal, as the validity of the dose-dependent J-shape association is tainted by conceptual, theoretical and methodological problems. A major impediment for a resolution on the matter is the lack of a life-long developmental approach to pinpoint alcohol's specific impact on the risk for cardio-vascular events (CVE). Using retrospective and prospective individual-level data of alcohol consumption (AC) we applied a model-based clustering technique to uncover life-course trajectories of AC and explored their links to CVE. Data stemmed from a random sub-cohort of a large-scale, longitudinal study conducted in the Netherlands (N=2288). Group Based Trajectory Model (GBTM) was applied to extract distinct progressions of AC over time. Stratified by sex, the association between the developmental trajectories and CVE was examined with multiple logistic regression models, with adjustment for traditional risk factors. GBTM analysis laid bare the heterogeneity of AC dynamics over the life-course, reiterating sex differences in drinking habits and CVE risk. AC temporal behaviors during adolescence and adulthood were diverse, but showed relative stability in in middle-age and elderly years. For males, adjusted odds for CVE differed among the uncovered developmental classes. The findings elicited supportive evidence for a J-shape, but with a new twist. Besides moderation the results indicate that onset, timing, duration and stability of AC over the life-course are major aspects to be accounted for when attempting to elucidate alcohol's cardio-vascular role. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  17. The expanded Global Registry of Acute Coronary Events: baseline characteristics, management practices, and hospital outcomes of patients with acute coronary syndromes.

    PubMed

    Goodman, Shaun G; Huang, Wei; Yan, Andrew T; Budaj, Andrzej; Kennelly, Brian M; Gore, Joel M; Fox, Keith A A; Goldberg, Robert J; Anderson, Frederick A

    2009-08-01

    The Global Registry of Acute Coronary Events (GRACE)-a prospective, multinational study of patients hospitalized with acute coronary syndromes (ACSs)-was designed to improve the quality of care for patients with an ACS. Expanded GRACE aims to test the feasibility of a simplified data collection tool and provision of quarterly feedback to index individual hospital management practices to an international reference cohort. We describe the objectives; study design; study and data management; and the characteristics, management, and hospital outcomes of patients > or =18 years old enrolled with a presumptive diagnosis of ACS. From 2001 to 2007, 31,982 patients were enrolled at 184 hospitals in 25 countries; 30% were diagnosed with ST-segment elevation myocardial infarction, 31% with non-ST-segment myocardial infarction, 26% with unstable angina, and 12% with another cardiac/noncardiac final diagnosis. The median age was 65 (interquartile range 55-75) years; 24% were >75 years old, and 33% were women. In general, increases were observed over time across the spectrum of ACS (1) in the use in the first 24 hours and at discharge of aspirin, clopidogrel, beta-blockers, and angiotensin-converting enzyme inhibitors/receptor blockers; (2) in the use at discharge of statins; (3) in the early use of glycoprotein IIb/IIIa inhibitors and low-molecular-weight heparin; and (4) in the use of cardiac catheterization and percutaneous coronary intervention. An increase in the use of primary percutaneous coronary intervention and a similar decrease in the use of fibrinolysis in ST-segment elevation myocardial infarction were also seen. Over the course of 7 years, general increases in the use of evidence-based therapies for ACS patients were observed in the expanded GRACE.

  18. Quantitative analysis of vascular parameters for micro-CT imaging of vascular networks with multi-resolution.

    PubMed

    Zhao, Fengjun; Liang, Jimin; Chen, Xueli; Liu, Junting; Chen, Dongmei; Yang, Xiang; Tian, Jie

    2016-03-01

    Previous studies showed that all the vascular parameters from both the morphological and topological parameters were affected with the altering of imaging resolutions. However, neither the sensitivity analysis of the vascular parameters at multiple resolutions nor the distinguishability estimation of vascular parameters from different data groups has been discussed. In this paper, we proposed a quantitative analysis method of vascular parameters for vascular networks of multi-resolution, by analyzing the sensitivity of vascular parameters at multiple resolutions and estimating the distinguishability of vascular parameters from different data groups. Combining the sensitivity and distinguishability, we designed a hybrid formulation to estimate the integrated performance of vascular parameters in a multi-resolution framework. Among the vascular parameters, degree of anisotropy and junction degree were two insensitive parameters that were nearly irrelevant with resolution degradation; vascular area, connectivity density, vascular length, vascular junction and segment number were five parameters that could better distinguish the vascular networks from different groups and abide by the ground truth. Vascular area, connectivity density, vascular length and segment number not only were insensitive to multi-resolution but could also better distinguish vascular networks from different groups, which provided guidance for the quantification of the vascular networks in multi-resolution frameworks.

  19. Acute Radiation Effects Resulting from Exposure to Solar Particle Event-Like Radiation

    NASA Astrophysics Data System (ADS)

    Kennedy, Ann; Cengel, Keith

    2012-07-01

    A major solar particle event (SPE) may place astronauts at significant risk for the acute radiation syndrome (ARS), which may be exacerbated when combined with other space flight stressors, such that the mission or crew health may be compromised. The National Space Biomedical Research Institute (NSBRI) Center of Acute Radiation Research (CARR) is focused on the assessment of risks of adverse biological effects related to the ARS in animal models exposed to space flight stressors combined with the types of radiation expected during an SPE. As part of this program, FDA-approved drugs that may prevent and/or mitigate ARS symptoms are being evaluated. The CARR studies are focused on the adverse biological effects resulting from exposure to the types of radiation, at the appropriate energies, doses and dose-rates, present during an SPE (and standard reference radiations, gamma rays or electrons). The ARS is a phased syndrome which often includes vomiting and fatigue. Other acute adverse biologic effects of concern are the loss of hematopoietic cells, which can result in compromised bone marrow and immune cell functions. There is also concern for skin damage from high SPE radiation doses, including burns, and resulting immune system dysfunction. Using 3 separate animal model systems (ferrets, mice and pigs), the major ARS biologic endpoints being evaluated are: 1) vomiting/retching and fatigue, 2) hematologic changes (with focus on white blood cells) and immune system changes resulting from exposure to SPE radiation with and without reduced weightbearing conditions, and 3) skin injury and related immune system functions. In all of these areas of research, statistically significant adverse health effects have been observed in animals exposed to SPE-like radiation. Countermeasures for the management of ARS symptoms are being evaluated. New research findings from the past grant year will be discussed. Acknowledgements: This research is supported by the NSBRI Center of Acute

  20. Vascular calcification: When should we interfere in chronic kidney disease patients and how?

    PubMed Central

    Sharaf El Din, Usama Abdel Azim; Salem, Mona Mansour; Abdulazim, Dina Ossama

    2016-01-01

    Chronic kidney disease (CKD) patients are endangered with the highest mortality rate compared to other chronic diseases. Cardiovascular events account for up to 60% of the fatalities. Cardiovascular calcifications affect most of the CKD patients. Most of this calcification is related to disturbed renal phosphate handling. Fibroblast growth factor 23 and klotho deficiency were incriminated in the pathogenesis of vascular calcification through different mechanisms including their effects on endothelium and arterial wall smooth muscle cells. In addition, deficient klotho gene expression, a constant feature of CKD, promotes vascular pathology and shares in progression of the CKD. The role of gut in the etio-pathogenesis of systemic inflammation and vascular calcification is a newly discovered mechanism. This review will cover the medical history, prevalence, pathogenesis, clinical relevance, different tools used to diagnose, the ideal timing to prevent or to withhold the progression of vascular calcification and the different medications and medical procedures that can help to prolong the survival of CKD patients. PMID:27648404

  1. Suitability of Exoseal Vascular Closure Device for Antegrade Femoral Artery Puncture Site Closure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schmelter, Christopher, E-mail: christopher.schmelter@klinikum-ingolstadt.de; Liebl, Andrea; Poullos, Nektarios

    Purpose. To assess the efficacy and safety of the Exoseal vascular closure device for antegrade puncture of the femoral artery. Methods. In a prospective study from February 2011 to January 2012, a total of 93 consecutive patients received a total of 100 interventional procedures via an antegrade puncture of the femoral artery. An Exoseal vascular closure device (6F) was used for closure in all cases. Puncture technique, duration of manual compression, and use of compression bandages were documented. All patients were monitored by vascular ultrasound and color-coded duplex sonography of their respective femoral artery puncture site within 12 to 36more » h after angiography to check for vascular complications. Results. In 100 antegrade interventional procedures, the Exoseal vascular closure device was applied successfully for closure of the femoral artery puncture site in 96 cases (96 of 100, 96.0 %). The vascular closure device could not be deployed in one case as a result of kinking of the vascular sheath introducer and in three cases because the bioabsorbable plug was not properly delivered to the extravascular space adjacent to the arterial puncture site, but instead fully removed with the delivery system (4.0 %). Twelve to 36 h after the procedure, vascular ultrasound revealed no complications at the femoral artery puncture site in 93 cases (93.0 %). Minor vascular complications were found in seven cases (7.0 %), with four cases (4.0 %) of pseudoaneurysm and three cases (3.0 %) of significant late bleeding, none of which required surgery. Conclusion. The Exoseal vascular closure device was safely used for antegrade puncture of the femoral artery, with a high rate of procedural success (96.0 %), a low rate of minor vascular complications (7.0 %), and no major adverse events.« less

  2. It is just a game: lack of association between watching football matches and the risk of acute cardiovascular events.

    PubMed

    Barone-Adesi, Francesco; Vizzini, Loredana; Merletti, Franco; Richiardi, Lorenzo

    2010-08-01

    The role of trigger factors in acute cardiovascular events has been much studied in the past few years. A recent study analysed changes in the rates of cardiac emergencies in Bavaria (Germany) during the last Football World Cup. The authors reported a 2.7-fold increase in the incidence of cardiac emergencies in the 12 h before and after football matches involving the German team, which sparked the debate on the necessity of the introduction of ad hoc cardiovascular preventive measures. We studied 25,159 hospital admissions for acute myocardial infarction (AMI) among the Italian population during three international football competitions: the World Cup 2002, the European Championship 2004 and the World Cup 2006. Poisson regression was used to estimate the relative risk of hospital admission for AMI on the days when football matches involving the Italian team were disputed, compared with the other days of the three competitions. Furthermore, we reviewed the available published studies regarding the association between football matches and the risk of cardiovascular events. We did not find an increase in the rates of admission for AMI on the days of football matches involving Italy in either the single competitions or the three competitions combined (relative risk 1.01; 95% confidence interval 0.98-1.05). We identified 10 studies published on this topic. With the exception of the recently published German study and two small Swiss studies, all relative risk estimates were between 0.7 and 1.3. The cardiovascular effects of watching football matches are likely to be, if anything, very small.

  3. Vascular ring

    MedlinePlus

    ... with aberrant subclavian and left ligamentum ateriosus; Congenital heart defect - vascular ring; Birth defect heart - vascular ring ... accounts for less than 1% of all congenital heart problems. The condition occurs as often in males ...

  4. [Laparascopic cholecystectomy in patients with acute cholecystitis].

    PubMed

    Tokin, A N; Chistiakov, A A; Mamalygina, L A; Zheliabin, D G; Osokin, G Iu

    2008-01-01

    Experience of diagnostics and treatment of 758 patients with acute cholecystitis was summarized. Authors attach the main importance to evaluation of ultrasound data and functional condition of respiratory and cardio-vascular sistem choosing the method of surgical treatment. Sparse use of laparoscopic cholecystectomy in treatment of acute cholecystitis compared with chronic may be explouned by presence of complications in patients which make problems in differentiation of tubular structures during the operation. Authors offered to use ultrasound dissection for clear identification of tubular structures and argon coagulation for hemostasis and safe mobilization of gall bladder. Stick to suggested tactics authors practically doubled the amount of performed laparoscopic cholecystectomies reducing at the same time the frequency of complications.

  5. The influence of a Vascular Surgery Hospitalist program on physician and patient satisfaction, resident education, and resource utilization.

    PubMed

    Cull, David L; Langan, Eugene M; Taylor, Spence M; Carsten, Christopher G; Tong, Angie; Johnson, Brent

    2013-10-01

    A number of surgery practice models have been developed to address general and trauma surgeon workforce shortages and on-call issues and to improve surgeon satisfaction. These include the creation of acute or urgent care surgery services and "surgical hospitalist" programs. To date, no practice models corresponding to those developed for general and trauma surgeons have been proposed to address these same issues among vascular surgeons or other surgical subspecialists. In 2003, our practice established a Vascular Surgery Hospitalist program. Since its inception nearly a decade ago, it has undergone several modifications. We reviewed hospital administrative databases and surveys of faculty, residents, and patients to evaluate the program's impact. Benefits of the Vascular Surgery Hospitalist program include improved surgeon satisfaction, resource utilization, timeliness of patient care, communication among referring physicians and ancillary staff, and resident teaching/supervision. Elements of this program may be applicable to a variety of surgical subspecialty settings. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  6. Acute and sub-chronic toxicity studies of honokiol microemulsion.

    PubMed

    Zhang, Qianqian; Li, Jianguo; Zhang, Wei; An, Quan; Wen, Jianhua; Wang, Aiping; Jin, Hongtao; Chen, Shizhong

    2015-04-01

    The purpose of this study was to investigate the acute and sub-chronic toxicity of honokiol microemulsion. In the acute toxicity tests, the mice were intravenously injected graded doses of honokiol microemulsion and were observed for toxic symptoms and mortality daily for 14 days. In the sub-chronic toxicity study, rats were injected honokiol microemulsion at doses of 100, 500, 2500 μg/kg body weight (BW) for 30 days. After 30 days treatment and 14 days recovery, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity tests, the estimated median lethal dosage (LD50) was 50.5mg/kg body weight in mice. In the sub-chronic toxicity tests, the non-toxic reaction dose was 500 μg/kg body weight. In each treatment group, degeneration or/and necrosis in vascular endothelial cells and structure change of vessel wall can be observed in the injection site (cauda vein) of a few animals while there were no changes in the vessels of other organs. The overall findings of this study indicate that the honokiol microemulsion is non-toxic up to 500 μg/kg body weight, and it has irritation to the vascular of the injection site which should be paid attention to in clinical medication. Copyright © 2015. Published by Elsevier Inc.

  7. Modulation of 11β-hydroxysteroid dehydrogenase as a strategy to reduce vascular inflammation.

    PubMed

    Hadoke, Patrick W F; Kipari, Tiina; Seckl, Jonathan R; Chapman, Karen E

    2013-05-01

    Atherosclerosis is a chronic inflammatory disease in which initial vascular damage leads to extensive macrophage and lymphocyte infiltration. Although acutely glucocorticoids suppress inflammation, chronic glucocorticoid excess worsens atherosclerosis, possibly by exacerbating systemic cardiovascular risk factors. However, glucocorticoid action within the lesion may reduce neointimal proliferation and inflammation. Glucocorticoid levels within cells do not necessarily reflect circulating levels due to pre-receptor metabolism by 11β-hydroxysteroid dehydrogenases (11β-HSDs). 11β-HSD2 converts active glucocorticoids into inert 11-keto forms. 11β-HSD1 catalyses the reverse reaction, regenerating active glucocorticoids. 11β-HSD2-deficiency/inhibition causes hypertension, whereas deficiency/inhibition of 11β-HSD1 generates a cardioprotective lipid profile and improves glycemic control. Importantly, 11β-HSD1-deficiency/inhibition is atheroprotective, whereas 11β-HSD2-deficiency accelerates atherosclerosis. These effects are largely independent of systemic risk factors, reflecting modulation of glucocorticoid action and inflammation within the vasculature. Here, we consider whether evidence linking the 11β-HSDs to vascular inflammation suggests these isozymes are potential therapeutic targets in vascular injury and atherosclerosis.

  8. Remodeling the Vascular Microenvironment of Glioblastoma with α-Particles.

    PubMed

    Behling, Katja; Maguire, William F; Di Gialleonardo, Valentina; Heeb, Lukas E M; Hassan, Iman F; Veach, Darren R; Keshari, Kayvan R; Gutin, Philip H; Scheinberg, David A; McDevitt, Michael R

    2016-11-01

    Tumors escape antiangiogenic therapy by activation of proangiogenic signaling pathways. Bevacizumab is approved for the treatment of recurrent glioblastoma, but patients inevitably develop resistance to this angiogenic inhibitor. We previously investigated targeted α-particle therapy with 225 Ac-E4G10 as an antivascular approach and showed increased survival and tumor control in a high-grade transgenic orthotopic glioblastoma model. Here, we investigated changes in tumor vascular morphology and functionality caused by 225 Ac-E4G10. We investigated remodeling of the tumor microenvironment in transgenic Ntva glioblastoma mice using a therapeutic 7.4-kBq dose of 225 Ac-E4G10. Immunofluorescence and immunohistochemical analyses imaged morphologic changes in the tumor blood-brain barrier microenvironment. Multicolor flow cytometry quantified the endothelial progenitor cell population in the bone marrow. Diffusion-weighted MR imaged functional changes in the tumor vascular network. The mechanism of drug action is a combination of remodeling of the glioblastoma vascular microenvironment, relief of edema, and depletion of regulatory T and endothelial progenitor cells. The primary remodeling event is the reduction of both endothelial and perivascular cell populations. Tumor-associated edema and necrosis were lessened, resulting in increased perfusion and reduced diffusion. Pharmacologic uptake of dasatinib into tumor was enhanced after α-particle therapy. Targeted antivascular α-particle radiation remodels the glioblastoma vascular microenvironment via a multimodal mechanism of action and provides insight into the vascular architecture of platelet-derived growth factor-driven glioblastoma. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  9. TRAF3 Epigenetic Regulation Is Associated With Vascular Recurrence in Patients With Ischemic Stroke.

    PubMed

    Gallego-Fabrega, Cristina; Carrera, Caty; Reny, Jean-Luc; Fontana, Pierre; Slowik, Agnieszka; Pera, Joanna; Pezzini, Alessandro; Serrano-Heras, Gemma; Segura, Tomás; Martí-Fàbregas, Joan; Muiño, Elena; Cullell, Natalia; Montaner, Joan; Krupinski, Jerzy; Fernandez-Cadenas, Israel

    2016-05-01

    Clopidogrel is one of the most used antiplatelet drugs in patients with cardiovascular disease. However, 16% to 50% of patients have a high on-clopidogrel platelet reactivity and an increased risk of ischemic events. The pathogenesis of high on-treatment platelet reactivity in patients with stroke is only partially explained by genetic variations. This study aims to find differentially methylated sites across the genome associated with vascular recurrence in ischemic stroke patients treated with clopidogrel. From a cohort of 1900 patients with ischemic stroke, we selected 42 patients treated with clopidogrel, including 21 with a recurrent vascular event and 21 without vascular recurrence during the first year of follow-up. Over 480 000 DNA methylation sites were analyzed across the genome. Differentially methylated CpG sites were identified by nonparametric testing using R. Replication analysis was performed in a new cohort of 191 subjects and results were correlated with platelet reactivity in a subset of 90 subjects using light transmission aggregometry. A total of 73 differentially methylated CpG sites (P<1×10(-05)) were identified; 3 of them were selected for further replication: cg03548645 (P=1.42×10(-05), TRAF3), cg09533145 (P=7.81×10(-06), ADAMTS2), and cg15107336 (P=1.89×10(-05), XRCC1). The cg03548645 CpG remained significant in the replication study (P=0.034), a deep analysis of this region revealed another methylation site associated with vascular recurrence, P=0.037. Lower cg03548645 (TRAF3) DNA methylation levels were correlated with an increased platelet aggregation (ρ=-0.29, P=0.0075). This study suggests for the first time that epigenetics may significantly contribute to the variability of clopidogrel response and recurrence of ischemic events in patients with stroke. © 2016 American Heart Association, Inc.

  10. Preclinical evaluation of hydrogel sealed fluropassivated indigenous vascular prosthesis.

    PubMed

    Unnikrishnan, Madathipat; Umashankar, P R; Viswanathan, Sidharth; Savlania, Ajay; Joseph, Roy; Muraleedharan, C V; Agrawal, Vivek; Shenoy, Sachin J; Krishnan, Lissy K; Mohanan, P V; Sabareeswaran, A

    2017-11-01

    Polyethylene terephthalate (PET) graft, designed and developed at our institute for vascular reconstruction, is porous to promote optimal incorporation and neointima formation, requiring pre-clotting or biomodification by sealing the pores before implantation. The objective of this study was to characterize, test and perform preclinical evaluation of hydrogel (alginate dialdehyde cross-linked gelatin) sealed fluoropassivated PET vascular prosthesis in pig model, so as to avoid pre-clotting, for its safety and efficacy before employing the indigenous and less expensive graft for clinical use. Hydrogel sealed, fluoropassivated PET vascular prosthesis were tested for haemocompatibility and toxicity followed by small animal toxicology tests and in vivo experiments in pigs receiving implantation at thoracic aorta. All 33 animals received test as well as control grafts with a plan for phased explantation at 2, 12 and 26 weeks. All animals underwent completion angiogram at the end of procedure as well as before graft explantation. Haemocompatibility tests for haemolysis and toxicity tests showed no adverse events in tested mice and rabbits. Completion angiogram showed intact anastamosis and patent graft in each animal in post-operative period and at explantation. Gross and histopathological examination showed well-encapsulated grafts, clean glistening neointima and no evidence of thrombus in both test and control grafts. Hydrogel sealed, fluoropassivated PET vascular prosthesis was found non-toxic, haemocompatible and remained patent in in vivo studies at planned intervals.

  11. Splenic infarction - A rare cause of acute abdominal pain following gastric surgery: A case series.

    PubMed

    Yazici, Pinar; Kaya, Cemal; Isil, Gurhan; Bozkurt, Emre; Mihmanli, Mehmet

    2015-01-01

    The dissection of splenic hilar lymph nodes in gastric cancer surgery is indispensable for treating gastric cancers located in the proximal third of the stomach. Splenic vascular injury is a matter of debate resulting on time or delayed splenectomy. We aimed to share our experience and plausible mechanisms causing this complication in two case reports. Two male patients with gastric cancer were diagnosed with acute splenic infarction following gastric surgery in the early postoperative period. Both underwent emergent exploratory laparotomy. Splenectomy was performed due to splenic infarction. Because we observed this rare complication in recent patients whose surgery was performed using vessel-sealing device for splenic hilar dissection, we suggested that extensive mobilization of the surrounding tissues of splenic vascular structures hilum using the vessel sealer could be the reason. In case of acute abdominal pain radiating to left shoulder, splenic complications should be taken into consideration in gastric cancer patients performed radical gastrectomy. Meticulous dissection of splenic hilar lymph nodes should be carried out to avoid any splenic vascular injury. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Total ginsenosides synergize with ulinastatin against septic acute lung injury and acute respir atory distress syndrome

    PubMed Central

    Sun, Rongju; Li, Yana; Chen, Wei; Zhang, Fei; Li, Tanshi

    2015-01-01

    Total ginsenosides synergize with ulinastatin (UTI) against septic acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We randomly divided 80 cases of severe sepsis-induced ALI and ARDS into a UTI group and a ginsenosides (GS)+UTI group. Continuous electrocardiac monitoring of pulse, respiratory rate, blood pressure, and heart rate; invasive hemodynamic monitoring; ventilator-assisted breathing and circulation support; and anti-infection as well as UTI treatment were given in the UTI group with GS treatment added for 7 consecutive days in the GS+UTI group. The indicators of pulmonary vascular permeability, pulmonary circulation, blood gases, and hemodynamics as well as APACHE II and ALI scores were detected on days 1, 3, and 7. The ALI score in the GS+UTI group was significantly decreased (P < 0.05) compared with that of the UTI group, and the indicators of pulmonary capillary permeability such as pulmonary vascular permeability index, extravascular lung water index, and oxygenation index, in the GS+UTI group improved significantly more than that of the UTI group. The indicators of hemodynamics and pulmonary circulation such as cardiac index, intrathoracic blood volume index, and central venous pressure improved significantly (P < 0.05), and the APACHE II score in the GS+UTI group was lower than that of the UTI group. GS can effectively collaborate with UTI against ALI and/or ARDS. PMID:26261640

  13. Medical costs in patients with heart failure after acute heart failure events: one-year follow-up study.

    PubMed

    Kim, Eugene; Kwon, Hye-Young; Baek, Sang Hong; Lee, Haeyoung; Yoo, Byung-Su; Kang, Seok-Min; Ahn, Youngkeun; Yang, Bong-Min

    2018-03-01

    This study investigated annual medical costs using real-world data focusing on acute heart failure. The data were retrospectively collected from six tertiary hospitals in South Korea. Overall, 330 patients who were hospitalized for acute heart failure between January 2011 and July 2012 were selected. Data were collected on their follow-up medical visits for 1 year, including medical costs incurred toward treatment. Those who died within the observational period or who had no records of follow-up visits were excluded. Annual per patient medical costs were estimated according to the type of medical services, and factors contributing to the costs using Gamma Generalized Linear Models (GLM) with log link were analyzed. On average, total annual medical costs for each patient were USD 6,199 (±9,675), with hospitalization accounting for 95% of the total expenses. Hospitalization cost USD 5,904 (±9,666) per patient. Those who are re-admitted have 88.5% higher medical expenditure than those who have not been re-admitted in 1 year, and patients using intensive care units have 19.6% higher expenditure than those who do not. When the number of hospital days increased by 1 day, medical expenses increased by 6.7%. Outpatient drug costs were not included. There is a possibility that medical expenses for AHF may have been under-estimated. It was found that hospitalization resulted in substantial costs for treatment of heart failure in South Korea, especially in patients with an acute heart failure event. Prevention strategies and appropriate management programs that would reduce both frequency of hospitalization and length of stay for patients with the underlying risk of heart failure are needed.

  14. Axon-glial disruption: the link between vascular disease and Alzheimer's disease?

    PubMed

    Horsburgh, Karen; Reimer, Michell M; Holland, Philip; Chen, Guiquan; Scullion, Gillian; Fowler, Jill H

    2011-08-01

    Vascular risk factors play a critical role in the development of cognitive decline and AD (Alzheimer's disease), during aging, and often result in chronic cerebral hypoperfusion. The neurobiological link between hypoperfusion and cognitive decline is not yet defined, but is proposed to involve damage to the brain's white matter. In a newly developed mouse model, hypoperfusion, in isolation, produces a slowly developing and diffuse damage to myelinated axons, which is widespread in the brain, and is associated with a selective impairment in working memory. Cerebral hypoperfusion, an early event in AD, has also been shown to be associated with white matter damage and notably an accumulation of amyloid. The present review highlights some of the published data linking white matter disruption to aging and AD as a result of vascular dysfunction. A model is proposed by which chronic cerebral hypoperfusion, as a result of vascular factors, results in both the generation and accumulation of amyloid and injury to white matter integrity, resulting in cognitive impairment. The generation of amyloid and accumulation in the vasculature may act to perpetuate further vascular dysfunction and accelerate white matter pathology, and as a consequence grey matter pathology and cognitive decline.

  15. Nitric oxide alterations following acute ductal constriction in the fetal lamb: a role for superoxide

    PubMed Central

    Hsu, Jong-Hau; Oishi, Peter; Wiseman, Dean A.; Hou, Yali; Chikovani, Omar; Datar, Sanjeev; Sajti, Eniko; Johengen, Michael J.; Harmon, Cynthia; Black, Stephen M.

    2010-01-01

    Acute partial compression of the fetal ductus arteriosus (DA) results in an initial abrupt increase in pulmonary blood flow (PBF), which is followed by a significant reduction in PBF to baseline values over the ensuing 2–4 h. We have previously demonstrated that this potent vasoconstricting response is due, in part, to an endothelin-1 (ET-1)-mediated decrease in nitric oxide synthase (NOS) activity. In addition, in vitro data demonstrate that ET-1 increases superoxide levels in pulmonary arterial smooth muscle cells and that oxidative stress alters NOS activity. Therefore, the objectives of this study were to determine the potential role of superoxide in the alterations of hemodynamics and NOS activity following acute ductal constriction in the late-gestation fetal lamb. Eighteen anesthetized near-term fetal lambs were instrumented, and a lung biopsy was performed. After a 48-h recovery, acute constriction of the DA was performed by inflating a vascular occluder. Polyethylene glycol-superoxide dismutase (PEG-SOD; 1,000–1,500 units/kg, n = 7) or PEG-alone (vehicle control group, n = 5) was injected into the pulmonary artery before ductal constriction. Six animals had a sham operation. In PEG-alone-treated lambs, acute ductal constriction rapidly decreased pulmonary vascular resistance (PVR) by 88%. However, by 4 h, PVR returned to preconstriction baseline. This vasoconstriction was associated with an increase in lung superoxide levels (82%), a decrease in total NOS activity (50%), and an increase in P-eNOS-Thr495 (52%) (P < 0.05). PEG-SOD prevented the increase of superoxide after ductal constriction, attenuated the vasoconstriction, preserved NOS activity, and increased P-eNOS Ser1177 (307%, P < 0.05). Sham procedure induced no changes. These data suggest that an acute decrease in NOS activity that is mediated, in part, by increased superoxide levels, and alterations in the phosphorylation status of the endothelial NOS isoform, underlie the pulmonary vascular

  16. Glio-vascular changes during ageing in wild-type and Alzheimer's disease-like APP/PS1 mice.

    PubMed

    Janota, C S; Brites, D; Lemere, C A; Brito, M A

    2015-09-16

    Vascular and glial involvement in the development of neurodegenerative disorders, such as Alzheimer's disease (AD), and age-related brain vulnerabilities have been suggested. Therefore, we sought to: (i) investigate which vascular and glial events are evident in ageing and/or AD, (ii) to establish the temporal evolution of vascular and glial changes in AD-like and wild-type (WT) mice and (iii) to relate them to amyloid-β (Aβ) peptide accumulation. We examined immunohistochemically hippocampi and cortex from APP/PS1dE9 and WT C57BL/6 mice along ageing and disease progression (young-adulthood, middle- and old-age). Ageing resulted in the increase in receptor for advanced glycation endproducts expression, as well as the entrance of thrombin and albumin in hippocampal parenchyma. In contrast, the loss of platelet-derived growth factor receptor-β (PDGFR-β) positive cells, in both regions, was only related to AD pathogenesis. Hypovascularization was affected by both ageing and AD in the hippocampus, but resulted from the interaction between both factors in the cortex. Astrogliosis was a result of AD in hippocampus and of both factors in cortex, while microgliosis was associated with fibrillar amyloid plaques in AD-like mice and with the interaction between both factors in each of the studied regions. In sum, these data show that senile plaques precede vascular and glial alterations only in hippocampus, whereas in cortex, vascular and glial alterations, namely the loss of PDGFR-β-positive cells and astrogliosis, accompanied the first senile plaques. Hence, this study points to vascular and glial events that co-exist in AD pathogenesis and age-related brain vulnerabilities. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Validity of administrative database code algorithms to identify vascular access placement, surgical revisions, and secondary patency.

    PubMed

    Al-Jaishi, Ahmed A; Moist, Louise M; Oliver, Matthew J; Nash, Danielle M; Fleet, Jamie L; Garg, Amit X; Lok, Charmaine E

    2018-03-01

    We assessed the validity of physician billing codes and hospital admission using International Classification of Diseases 10th revision codes to identify vascular access placement, secondary patency, and surgical revisions in administrative data. We included adults (≥18 years) with a vascular access placed between 1 April 2004 and 31 March 2013 at the University Health Network, Toronto. Our reference standard was a prospective vascular access database (VASPRO) that contains information on vascular access type and dates of placement, dates for failure, and any revisions. We used VASPRO to assess the validity of different administrative coding algorithms by calculating the sensitivity, specificity, and positive predictive values of vascular access events. The sensitivity (95% confidence interval) of the best performing algorithm to identify arteriovenous access placement was 86% (83%, 89%) and specificity was 92% (89%, 93%). The corresponding numbers to identify catheter insertion were 84% (82%, 86%) and 84% (80%, 87%), respectively. The sensitivity of the best performing coding algorithm to identify arteriovenous access surgical revisions was 81% (67%, 90%) and specificity was 89% (87%, 90%). The algorithm capturing arteriovenous access placement and catheter insertion had a positive predictive value greater than 90% and arteriovenous access surgical revisions had a positive predictive value of 20%. The duration of arteriovenous access secondary patency was on average 578 (553, 603) days in VASPRO and 555 (530, 580) days in administrative databases. Administrative data algorithms have fair to good operating characteristics to identify vascular access placement and arteriovenous access secondary patency. Low positive predictive values for surgical revisions algorithm suggest that administrative data should only be used to rule out the occurrence of an event.

  18. History of erectile dysfunction as a predictor of poor physical performance after an acute myocardial infarction.

    PubMed

    Compostella, Leonida; Compostella, Caterina; Truong, Li Van Stella; Russo, Nicola; Setzu, Tiziana; Iliceto, Sabino; Bellotto, Fabio

    2017-03-01

    Background Erectile dysfunction may predict future cardiovascular events and indicate the severity of coronary artery disease in middle-aged men. The aim of this study was to evaluate whether erectile dysfunction (expression of generalized macro- and micro-vascular pathology) could predict reduced effort tolerance in patients after an acute myocardial infarction. Patients and methods One hundred and thirty-nine male patients (60 ± 12 years old), admitted to intensive cardiac rehabilitation 13 days after a complicated acute myocardial infarction, were evaluated for history of erectile dysfunction using the International Index of Erectile Function questionnaire. Their physical performance was assessed by means of two six-minute walk tests (performed two weeks apart) and by a symptom limited cardiopulmonary exercise test (CPET). Results Patients with erectile dysfunction (57% of cases) demonstrated poorer physical performance, significantly correlated to the degree of erectile dysfunction. After cardiac rehabilitation, they walked shorter distances at the final six-minute walk test (490 ± 119 vs. 564 ± 94 m; p < 0.001); at CPET they sustained lower workload (79 ± 28 vs. 109 ± 34 W; p < 0.001) and reached lower oxygen uptake at peak effort (18 ± 5 vs. 21 ± 5 ml/kg per min; p = 0.003) and at anaerobic threshold (13 ± 3 vs.16 ± 4 ml/kg per min; p = 0.001). The positive predictive value of presence of erectile dysfunction was 0.71 for low peak oxygen uptake (<20 ml/kg per min) and 0.69 for reduced effort capacity (W-max <100 W). Conclusions As indicators of generalized underlying vascular pathology, presence and degree of erectile dysfunction may predict the severity of deterioration of effort tolerance in post-acute myocardial infarction patients. In the attempt to reduce the possibly associated long-term risk, an optimization of type, intensity and duration of cardiac rehabilitation should be

  19. Hydrogen sulfide protects endothelial nitric oxide function under conditions of acute oxidative stress in vitro.

    PubMed

    Al-Magableh, Mohammad R; Kemp-Harper, Barbara K; Ng, Hooi H; Miller, Alyson A; Hart, Joanne L

    2014-01-01

    The aim of this study was to examine the ability of H2S, released from NaHS to protect vascular endothelial function under conditions of acute oxidative stress by scavenging superoxide anions (O2(-)) and suppressing vascular superoxide anion production. O2(-) was generated in Krebs' solution by reacting hypoxanthine with xanthine oxidase (Hx-XO) or with the O2(-) generator pyrogallol to model acute oxidative stress in vitro. O2(-) generation was measured by lucigenin-enhanced chemiluminescence. Functional responses in mouse aortic rings were assessed using a small vessel myograph. NaHS scavenged O2(-) in a concentration-dependent manner. Isolated aortic rings exposed to either Hx-XO or pyrogallol displayed significantly attenuated maximum vasorelaxation responses to the endothelium-dependent vasodilator acetylcholine, and significantly reduced NO bioavailability, which was completely reversed if vessels were pre-incubated with NaHS (100 μM). NADPH-stimulated aortic O2(-) production was significantly attenuated by the NADPH oxidase inhibitor diphenyl iodonium. Prior treatment of vessels with NaHS (100 nM-100 μM; 30 min) inhibited NADPH-stimulated aortic O2(-) production in a concentration-dependent manner. This effect persisted when NaHS was washed out prior to measuring NADPH-stimulated O2(-) production. These data show for the first time that NaHS directly scavenges O2(-) and suppresses vascular NADPH oxidase-derived O2(-) production in vitro. Furthermore, these properties protect endothelial function and NO bioavailability in an in vitro model of acute oxidative stress. These results suggest that H2S can elicit vasoprotection by both scavenging O2(-) and by reducing vascular NADPH oxidase-derived O2(-) production.

  20. Reduction in recurrent cardiovascular events with prasugrel compared with clopidogrel in patients with acute coronary syndromes from the TRITON-TIMI 38 trial

    PubMed Central

    Murphy, Sabina A.; Antman, Elliott M.; Wiviott, Stephen D.; Weerakkody, Govinda; Morocutti, Giorgio; Huber, Kurt; Lopez-Sendon, Jose; McCabe, Carolyn H.; Braunwald, Eugene

    2008-01-01

    Aims In the TRITON-TIMI 38 trial, greater platelet inhibition with prasugrel reduced the first occurrence of the primary endpoint (cardiovascular death, MI, or stroke) compared with clopidogrel in patients with an acute coronary syndrome (ACS) undergoing planned percutaneous coronary intervention. We hypothesized that prasugrel would reduce not only first events but also recurrent primary endpoint events and therefore total events compared with clopidogrel. Methods and results Poisson regression analysis was performed to compare the number of occurrences of the primary endpoint between prasugrel and clopidogrel in TRITON-TIMI 38. Landmark analytic methods were used to evaluate the risk of a recurrent primary endpoint event following an initial non-fatal endpoint event. Among patients with an initial non-fatal event, second events were significantly reduced with prasugrel compared to clopidogrel (10.8 vs. 15.4%, HR 0.65, 95% CI 0.46–0.92; P = 0.016), as was CV death following the non-fatal event (3.7 vs. 7.1%, HR 0.46, 95% CI 0.25–0.82; P = 0.008). Overall there was a reduction of 195 total primary efficacy events with prasugrel vs. clopidogrel (rate ratio 0.79, 95% CI 0.71–0.87; P < 0.001). Recurrent bleeding events occurred infrequently (TIMI major non-CABG bleeds: four with prasugrel and two with clopidogrel). Study drug discontinuation was frequent following the initial major bleeding event (42% of patients discontinued study drug). Conclusion While standard statistical analytic techniques for clinical trials censor patients who experience a component of the primary composite endpoint, total cardiovascular events remain important to both patients and clinicians. Prasugrel, a more potent anti-platelet agent, reduced both first and subsequent cardiovascular events compared with clopidogrel in patients with ACS. PMID:18682445

  1. Vascular Endothelial Function Assessed by Postischemic Diastolic Blood Pressure Is Associated with Acclimatization and Acute Mountain Sickness.

    PubMed

    He, Lipeng; Jiang, Yu; Su, Hai; Li, Juxiang; Cheng, Xiaoshu

    2016-03-01

    This study assessed whether the brachial diastolic blood pressure (DBP) decline induced by 5-minute arm ischemia is associated with acclimatization and acute mountain sickness (AMS). Forty-two age- and body mass index-matched young male residents at sea level (<400 m) or moderate altitude (1000-2000 m above sea level) were enrolled. All subjects had never been to 3200 m before. Brachial BP was measured at a station at 1380 m altitude before and 1, 5, and 10 minutes after right arm ischemia. AMS score was evaluated after 3-day training at a high altitude of 3200 m. In moderate altitude versus sea-level residents: (1) systolic BP curves for both arms overlapped well; (2) mean right arm DBP decline post right arm ischemia was larger, while left arm, which was not subjected to ischemia, did not show DBP decline in either group; and (3) AMS scores were significantly lower (3.19 ± 2.16 vs. 5.52 ± 4.58, p = 0.043) in those residing at moderate altitude compared to those from low altitude. There was a low negative correlation between AMS score and right arm area between curves-DBP (r = -0.320, p = 0.039). Moderate altitude relative to sea-level residents had a larger mean postischemic DBP decline in weak but significant association with lower mean AMS score at 3200 m. These data suggest that differences in vascular endothelial function related to altitude of residence persist during travel to high altitude and might contribute to AMS risk.

  2. The effect of periodontal therapy on neopterin and vascular cell adhesion molecule-1 levels in chronic periodontitis patients with and without acute myocardial infarction: a case-control study.

    PubMed

    Turgut Çankaya, Zeynep; Bodur, Ayşen; Taçoy, Gülten; Ergüder, Imge; Aktuna, Derya; Çengel, Atiye

    2018-04-05

    The presence of neopterin in gingival crevicular fluid (GCF) is a marker for local and acute immune activation, and the presence of vascular cell adhesion molecule (VCAM-1) in GCF is accepted as a marker for chronic vascular inflammation. This study aimed to evaluate effects of periodontal treatment on GCF levels of neopterin and VCAM-1 in patients with chronic periodontitis (CP) with acute myocardial infarction (AMI) compared with systemically healthy CP patients. Sixty subjects (20 CP patients with AMI, 20 healthy CP patients, and 20 healthy controls) were included. GCF samples were analyzed at baseline and after 3 and 6 months, and the probing pocket depth (PD), clinical attachment level (CAL), bleeding on probing, gingival (GI) and plaque (PI) indices were recorded. We determined neopterin and VCAM-1 levels (concentration and total amount) using enzyme-linked immunosorbent assay (ELISA). No significant differences were seen between the AMI+CP and CP groups for PI, GI, GCF levels of neopterin and VCAM-1 at baseline. The number of teeth with 5 mm≤CAL<7 mm and CAL≥7 mm were significantly increased in the AMI+CP group at baseline. There were no significant differences between the AMI+CP and CP for PI, CAL, GCF volumes, and the AMI+CP group had the highest clinical improvement in the number of teeth with 5 mm≤CAL<7 mm at the sixth month. There were significant positive correlations between clinical periodontal inflammation and the presence of neopterin and VCAM-1 in GCF prior to and following periodontal treatment, and between the GCF volume and clinical parameters. Data suggest that the total amount and concentration of neopterin and VCAM-1 in GCF seemed to be closely associated with periodontal disease severity in CP patients with AMI. Moreover, the results of our study demonstrate that the past periodontal status is potentially correlated between groups, with similar periodontal disease severity.

  3. MOrtality and infectious complications of therapeutic EndoVAscular interventional radiology: a systematic and meta-analysis protocol.

    PubMed

    Mellouk Aid, Kaoutar; Tchala Vignon Zomahoun, Hervé; Soulaymani, Abdelmajid; Lebascle, Karin; Silvera, Stephane; Astagneau, Pascal; Misset, Benoit

    2017-04-24

    Endovascular interventional radiology (EIR) is an increasingly popular, mini invasive treatment option for patient with symptomatic vascular disease. The EIR practiced by qualified hands is an effective, well-tolerated procedure that offers relief of patient's symptoms with a low risk of complications. During acute post procedural period, immediate complications may relate to vascular access, restenosis, thromboembolic events, uterine ischemia, infection, necrosis, sepsis, ICU stay, surgical recovery, pain management, treatment failure, and death. Moreover, additional non-life-threatening complications exist, but they are not well described and represent disparate information. A range of databases will be screened consulted to identify the relevant studies: PubMed, EMBASE, The Cochrane Library, NosoBase, and Google Scholar (to identify articles not yet indexed). Scientist librarian used Medical Subject Headings (MeSH) and free terms to construct the search strategy in PubMed. This search strategy will be adapted in other databases. Two coauthors will independently select the relevant studies, extract the relevant data, and assess the risk of bias in the included studies. Any disagreements between the two authors will be solved by a third author. This systematic review will provide a synthesis of EIR complications. The spotlighted results will be analyzed in order to provide a state-of-knowledge synopsis of the current evidence base in relation to the epidemiology of the infectious complications after EIR. In the event of conclusive results, our findings will serve as a reference background to assess guidelines on reality of the problem of the infections linked to endovascular interventional radiology and to formulate of assumptions and propose preventive measures, based on the results of our investigations. These propositions will aim to reduce the risk and/or the severity of these complications in the concerned population in favor a positive medical economics

  4. Lung heparan sulfates modulate Kfc during increased vascular pressure: evidence for glycocalyx-mediated mechanotransduction

    PubMed Central

    Cluff, Mark; Kingston, Joseph; Hill, Denzil; Chen, Haiyan; Hoehne, Soeren; Malleske, Daniel T.; Kaur, Rajwinederjit

    2012-01-01

    Lung endothelial cells respond to changes in vascular pressure through mechanotransduction pathways that alter barrier function via non-Starling mechanism(s). Components of the endothelial glycocalyx have been shown to participate in mechanotransduction in vitro and in systemic vessels, but the glycocalyx's role in mechanosensing and pulmonary barrier function has not been characterized. Mechanotransduction pathways may represent novel targets for therapeutic intervention during states of elevated pulmonary pressure such as acute heart failure, fluid overload, and mechanical ventilation. Our objective was to assess the effects of increasing vascular pressure on whole lung filtration coefficient (Kfc) and characterize the role of endothelial heparan sulfates in mediating mechanotransduction and associated increases in Kfc. Isolated perfused rat lung preparation was used to measure Kfc in response to changes in vascular pressure in combination with superimposed changes in airway pressure. The roles of heparan sulfates, nitric oxide, and reactive oxygen species were investigated. Increases in capillary pressure altered Kfc in a nonlinear relationship, suggesting non-Starling mechanism(s). nitro-l-arginine methyl ester and heparanase III attenuated the effects of increased capillary pressure on Kfc, demonstrating active mechanotransduction leading to barrier dysfunction. The nitric oxide (NO) donor S-nitrosoglutathione exacerbated pressure-mediated increase in Kfc. Ventilation strategies altered lung NO concentration and the Kfc response to increases in vascular pressure. This is the first study to demonstrate a role for the glycocalyx in whole lung mechanotransduction and has important implications in understanding the regulation of vascular permeability in the context of vascular pressure, fluid status, and ventilation strategies. PMID:22160307

  5. Acute stress affects prospective memory functions via associative memory processes.

    PubMed

    Szőllősi, Ágnes; Pajkossy, Péter; Demeter, Gyula; Kéri, Szabolcs; Racsmány, Mihály

    2018-01-01

    Recent findings suggest that acute stress can improve the execution of delayed intentions (prospective memory, PM). However, it is unclear whether this improvement can be explained by altered executive control processes or by altered associative memory functioning. To investigate this issue, we used physical-psychosocial stressors to induce acute stress in laboratory settings. Then participants completed event- and time-based PM tasks requiring the different contribution of control processes and a control task (letter fluency) frequently used to measure executive functions. According to our results, acute stress had no impact on ongoing task performance, time-based PM, and verbal fluency, whereas it enhanced event-based PM as measured by response speed for the prospective cues. Our findings indicate that, here, acute stress did not affect executive control processes. We suggest that stress affected event-based PM via associative memory processes. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Plasma cytokines eotaxin, MIP-1α, MCP-4, and vascular endothelial growth factor in acute lower respiratory tract infection.

    PubMed

    Relster, Mette Marie; Holm, Anette; Pedersen, Court

    2017-02-01

    Major overlaps of clinical characteristics and the limitations of conventional diagnostic tests render the initial diagnosis and clinical management of pulmonary disorders difficult. In this pilot study, we analyzed the predictive value of eotaxin, macrophage inflammatory protein 1 alpha (MIP-1α), monocyte chemoattractant protein 4 (MCP-4), and vascular endothelial growth factor (VEGF) in 40 patients hospitalized with acute lower respiratory tract infections (LRTI). The cytokines contribute to the pathogenesis of several inflammatory respiratory diseases, indicating a potential as markers for LRTI. Patients were stratified according to etiology and severity of LRTI, based on baseline C-reactive protein and CURB-65 scores. Using a multiplex immunoassay of plasma, levels of eotaxin and MCP-4 were shown to increase from baseline until day 6 after admission to hospital. The four cytokines were unable to predict the etiology and severity. Eotaxin and MCP-4 were significantly lower in patients with C-reactive protein ≥100, and MIP-1α was significantly higher in the patients with CURB-65 > 3, but the predictive power was low. In conclusion, further evaluation, including more patients, is required to assess the full potential of eotaxin, MCP-4, MIP-1α, and VEGF as biomarkers for LRTI because of their low predictive power and a high interindividual variation of cytokine levels. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  7. Gastroschisis, destructive brain lesions, and placental infarction in the second trimester suggest a vascular pathogenesis.

    PubMed

    Folkerth, Rebecca D; Habbe, Donald M; Boyd, Theonia K; McMillan, Kristin; Gromer, Jessica; Sens, Mary Ann; Elliott, Amy J

    2013-01-01

    The cause and pathogenesis of gastroschisis are uncertain. We report the autopsy and placental pathology of a stillbirth at 20 gestational weeks, in which gastroschisis was accompanied by destructive lesions in the cerebral cortex and brainstem, as well as cardiac calcification, consistent with ischemic injury during the 2nd trimester. An important potential underlying mechanism explaining the fetal abnormalities is the presence of infarcts in the placenta, indicative at this gestational age of maternal vascular underperfusion. The association of gastroschisis with ischemic lesions in the brain, heart, and placenta in this case supports the concept that gastroschisis, at least in some instances, may result from vascular event(s) causing disruption of the fetal abdominal wall and resulting in the extrusion of the abdominal organs, as well as hypoxic-ischemic brain and cardiac injury.

  8. Management of acute coronary syndromes in Maghreb countries: The ACCESS (ACute Coronary Events - a multinational Survey of current management Strategies) registry.

    PubMed

    Moustaghfir, Abdelhamid; Haddak, Mohand; Mechmeche, Rachid

    2012-11-01

    The burden of cardiovascular diseases is anticipated to rise in developing countries. We sought to describe the epidemiology, management, and clinical outcomes of patients hospitalized with acute coronary syndromes (ACS) in three countries in western North Africa. Adult patients hospitalized with a diagnosis of ACS were enrolled in the prospective ACute Coronary Events - a multinational Survey of current management Strategies (ACCESS) registry over a 13-month period (January 2007 to January 2008). We report on patients enrolled at sites in Algeria, Morocco and Tunisia. A standardized form was used to collect data on patient characteristics, treatments and outcomes. A total of 1687 patients with confirmed ACS were enrolled (median age 59 [interquartile range 52, 68] years; 76% men), 59% with ST-elevation myocardial infarction (STEMI) and 41% with non-ST-elevation ACS (NSTE-ACS). During hospitalization, most patients received aspirin (96%) and a statin (90%), 83% received a beta-blocker and 74% an angiotensin-converting enzyme inhibitor. Among eligible STEMI patients, 42% (419/989) did not receive fibrinolysis or undergo percutaneous coronary intervention. All-cause death at 12 months was 8.1% and did not differ significantly between patients with STEMI or NSTE-ACS (8.3% vs 7.7%, respectively; Log-rank test P=0.82). Clinical factors associated with higher risk of death at 12 months included cardiac arrest, cardiogenic shock, bleeding episodes and diabetes, while percutaneous coronary intervention and male sex were associated with lower risk. In this observational study of ACS patients from three Maghreb countries, the use of evidence-based pharmacological therapies for ACS was quite high; however, 42% of the patients with STEMI were not given any form of reperfusion therapy. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  9. Increased Serum Alkaline Phosphatase and Serum Phosphate as Predictors of Mortality after Stroke

    PubMed Central

    S, Pratibha; JB, Agadi

    2014-01-01

    Context: Serum Alkaline phosphatase (ALP) & phosphate are considered to be indicators of vascular calcification. Link between bone metabolism, vascular calcification, cardiovascular events have been well studied in chronic kidney disease and ischemic heart disease. Aims: To determine that increased serum phosphate and alkaline phosphatase are predictors of mortality rates and recurrent vascular events in stroke. Materials and Methods: Sixty patients admitted with acute stroke (ischemic & haemorrhagic) were included in the study. Their baseline clinical characteristics and biochemical parameters including serum ALP and phosphate were noted. All patients were followed up for a period of one year. The all- cause mortality, the mortality due to cardiovascular events and recurrent vascular events without death were noted during the follow up. Statistical analyses were done to look for any correlation between mortality and baseline levels of serum ALP and phosphate. Results: Of the 60 patients, 8 (13.3%) patients were lost for follow up. Fourteen (26.9%) patients died; of which 12 deaths were due to vascular causes and 2 deaths were due to non vascular causes. Increasing levels of serum ALP and phosphate correlated with all cause mortality and recurrent vascular events without death Conclusion: Serum ALP and phosphate prove to be cost effective prognostic indicator of mortality and recurrent vascular events in stroke. This finding has to be confirmed with studies including larger population. Further research on ALP inhibitors, Vitamin D analogues and phosphate binders to improve mortality in stroke population can be encouraged. PMID:25300293

  10. Increased serum alkaline phosphatase and serum phosphate as predictors of mortality after stroke.

    PubMed

    S, Pratibha; S, Praveen-Kumar; Jb, Agadi

    2014-08-01

    Serum Alkaline phosphatase (ALP) & phosphate are considered to be indicators of vascular calcification. Link between bone metabolism, vascular calcification, cardiovascular events have been well studied in chronic kidney disease and ischemic heart disease. To determine that increased serum phosphate and alkaline phosphatase are predictors of mortality rates and recurrent vascular events in stroke. Sixty patients admitted with acute stroke (ischemic & haemorrhagic) were included in the study. Their baseline clinical characteristics and biochemical parameters including serum ALP and phosphate were noted. All patients were followed up for a period of one year. The all- cause mortality, the mortality due to cardiovascular events and recurrent vascular events without death were noted during the follow up. Statistical analyses were done to look for any correlation between mortality and baseline levels of serum ALP and phosphate. Of the 60 patients, 8 (13.3%) patients were lost for follow up. Fourteen (26.9%) patients died; of which 12 deaths were due to vascular causes and 2 deaths were due to non vascular causes. Increasing levels of serum ALP and phosphate correlated with all cause mortality and recurrent vascular events without death Conclusion: Serum ALP and phosphate prove to be cost effective prognostic indicator of mortality and recurrent vascular events in stroke. This finding has to be confirmed with studies including larger population. Further research on ALP inhibitors, Vitamin D analogues and phosphate binders to improve mortality in stroke population can be encouraged.

  11. Event-Related Potential responses to the acute and chronic effects of alcohol in adolescent and adult Wistar rats

    PubMed Central

    Ehlers, Cindy L.; Desikan, Anita; Wills, Derek N.

    2014-01-01

    Background The present study explored the hypothesis that adolescent ethanol exposure may cause long lasting changes in ethanol sensitivity by exploring the age-related effects of acute alcohol on intoxication and on event-related potential (ERP) responses to acoustic stimuli in ethanol naïve adolescent and adult male Wistar rats and in adult rats that were exposed to chronic ethanol/control conditions during adolescence. Methods Ethanol naïve adolescent (postnatal day 32 (PD32)) and adult male rats (PD99) were included in the first study. In a second study, rats were exposed to 5 weeks of ethanol vapor (Blood ethanol concentrations @ 175 mg%) or air from PD24 to PD59 and allowed to mature until PD90. In both studies rats were implanted with cortical recording electrodes, and the effects of acute ethanol (0.0, 1.5, and 3.0 g/kg) on behavioral and ERP responses were assessed. Results Adolescents were found to have higher amplitude and longer latency P3a and P3b components at baseline as compared to adult rats, and ethanol was found to produce a robust dose-dependent increase in the latency of the P3a and P3b components of the auditory ERP recorded in cortical sites in both adolescents and adults. However, ethanol produced significantly larger delays in P3a and P3b latencies in adults as compared to adolescents. Acute ethanol administration was also found to produce a robust dose dependent increase in the latency of the P3a and P3b components in adult animals exposed to ethanol vapor as adolescents and air exposed controls; however, larger acute ethanol-induced increases in P3a and P3b latencies were seen in controls as compared to adolescent vapor exposed rats. Conclusions Adolescent rats have a less intense P3 latency response to acute ethanol administration when compared to adult rats. Exposure to chronic ethanol during adolescence can cause “retention” of the adolescent phenotype of reduced P3 latency sensitivity to ethanol. PMID:24483322

  12. Cerebral Vascular Injury in Traumatic Brain Injury.

    PubMed

    Kenney, Kimbra; Amyot, Franck; Haber, Margalit; Pronger, Angela; Bogoslovsky, Tanya; Moore, Carol; Diaz-Arrastia, Ramon

    2016-01-01

    Traumatic cerebral vascular injury (TCVI) is a very frequent, if not universal, feature after traumatic brain injury (TBI). It is likely responsible, at least in part, for functional deficits and TBI-related chronic disability. Because there are multiple pharmacologic and non-pharmacologic therapies that promote vascular health, TCVI is an attractive target for therapeutic intervention after TBI. The cerebral microvasculature is a component of the neurovascular unit (NVU) coupling neuronal metabolism with local cerebral blood flow. The NVU participates in the pathogenesis of TBI, either directly from physical trauma or as part of the cascade of secondary injury that occurs after TBI. Pathologically, there is extensive cerebral microvascular injury in humans and experimental animal, identified with either conventional light microscopy or ultrastructural examination. It is seen in acute and chronic TBI, and even described in chronic traumatic encephalopathy (CTE). Non-invasive, physiologic measures of cerebral microvascular function show dysfunction after TBI in humans and experimental animal models of TBI. These include imaging sequences (MRI-ASL), Transcranial Doppler (TCD), and Near InfraRed Spectroscopy (NIRS). Understanding the pathophysiology of TCVI, a relatively under-studied component of TBI, has promise for the development of novel therapies for TBI. Published by Elsevier Inc.

  13. Vascular closure devices in stroke patients receiving tissue plasminogen activator: A retrospective analysis from an academic tertiary medical center and a teaching community hospital stroke database.

    PubMed

    Patil, Mangaladevi S; Jayaraman, Mahesh V; Ahn, Sun H

    2017-06-01

    To determine the safety and effectiveness of vascular closure devices in prevention of access site complications in acute stroke patient receiving intravenous (IV) and/or intra-arterial (IA) IV tissue plasminogen activator (tPA). All patients with acute stroke onset treated with IV and/or IA tPA closed with vascular closure device and adult age (>18 years) were identified from an academic tertiary medical center and a teaching community hospital stroke database for 9 years (from March 2005 to June 2014). A total of 69 patients were included in the study. The mean age was 68.86±16.70 years and 49.2% female. All accesses were under fluoroscopic guidance into the right common femoral artery. We observed a 5.8% complication rate in patients receiving IV and/or IA tPA closed with vascular closure device. Access site complications included 3 cases of hematoma and 1 case of residual oozing. One patient required transfusion due to access site hematoma. Three patients were on aspirin and heparin and 1 was on no prior anticoagulation. Vascular closure device access site hemorrhagic complication rate in those receiving IV and/or IA tPA is low and similar to reported rates in those not receiving thrombolytic therapy. Vascular closure device use in patients receiving thrombolytic therapy is safe and effectively achieves hemostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Prognostic Value of Urinary Neutrophil Gelatinase-Associated Lipocalin on the First Day of Admission for Adverse Events in Patients With Acute Decompensated Heart Failure.

    PubMed

    Nakada, Yasuki; Kawakami, Rika; Matsui, Masaru; Ueda, Tomoya; Nakano, Tomoya; Takitsume, Akihiro; Nakagawa, Hitoshi; Nishida, Taku; Onoue, Kenji; Soeda, Tsunenari; Okayama, Satoshi; Watanabe, Makoto; Kawata, Hiroyuki; Okura, Hiroyuki; Saito, Yoshihiko

    2017-05-18

    Urinary neutrophil gelatinase-associated lipocalin (U-NGAL) is an early predictor of acute kidney injury and adverse events in various diseases; however, in acute decompensated heart failure patients, its significance remains poorly understood. This study aimed to investigate the prognostic value of U-NGAL on the first day of admission for the occurrence of acute kidney injury and long-term outcomes in acute decompensated heart failure patients. We studied 260 acute decompensated heart failure patients admitted to our department between 2011 and 2014 by measuring U-NGAL in 24-hour urine samples collected on the first day of admission. Primary end points were all-cause death, cardiovascular death, and heart failure admission. Patients were divided into 2 groups according to their median U-NGAL levels (32.5 μg/gCr). The high-U-NGAL group had a significantly higher occurrence of acute kidney injury during hospitalization than the low-U-NGAL group ( P =0.0012). Kaplan-Meier analysis revealed that the high-U-NGAL group exhibited a worse prognosis than the low-U-NGAL group in all-cause death (hazard ratio 2.07; 95%CI 1.38-3.12, P =0.0004), cardiovascular death (hazard ratio 2.29; 95%CI 1.28-4.24, P =0.0052), and heart failure admission (hazard ratio 1.77; 95%CI 1.13-2.77, P =0.0119). The addition of U-NGAL to the estimated glomerular filtration rate significantly improved the predictive accuracy of all-cause mortality ( P =0.0083). In acute decompensated heart failure patients, an elevated U-NGAL level on the first day of admission was related to the development of clinical acute kidney injury and independently associated with poor prognosis. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  15. Stenting for Acute Aortic Dissection with Malperfusion as “Bridge Therapy”

    PubMed Central

    Fujita, Wakako; Taniguchi, Satoshi; Daitoku, Kazuyuki; Fukuda, Ikuo

    2010-01-01

    The most common treatment of acute type A aortic dissection is immediate surgical repair. However, early surgery for acute dissections with peripheral vascular compromise carries a high mortality rate. Herein, we report a case in which we placed percutaneous endovascular stents in a type A dissection patient before proceeding with proximal aortic repair. Bare-metal stents were placed into the obliterated true channel of the abdominal aorta and the left external iliac artery. Endovascular stenting immediately relieved the lower-left-extremity ischemic symptoms, and the patient underwent hemi-arch replacement 7 days after the procedure. Stent placement for patients who have acute aortic dissection with malperfusion can be used as “bridge therapy.” PMID:21224949

  16. Comparison of RISK-PCI, GRACE, TIMI risk scores for prediction of major adverse cardiac events in patients with acute coronary syndrome.

    PubMed

    Jakimov, Tamara; Mrdović, Igor; Filipović, Branka; Zdravković, Marija; Djoković, Aleksandra; Hinić, Saša; Milić, Nataša; Filipović, Branislav

    2017-12-31

    To compare the prognostic performance of three major risk scoring systems including global registry for acute coronary events (GRACE), thrombolysis in myocardial infarction (TIMI), and prediction of 30-day major adverse cardiovascular events after primary percutaneous coronary intervention (RISK-PCI). This single-center retrospective study involved 200 patients with acute coronary syndrome (ACS) who underwent invasive diagnostic approach, ie, coronary angiography and myocardial revascularization if appropriate, in the period from January 2014 to July 2014. The GRACE, TIMI, and RISK-PCI risk scores were compared for their predictive ability. The primary endpoint was a composite 30-day major adverse cardiovascular event (MACE), which included death, urgent target-vessel revascularization (TVR), stroke, and non-fatal recurrent myocardial infarction (REMI). The c-statistics of the tested scores for 30-day MACE or area under the receiver operating characteristic curve (AUC) with confidence intervals (CI) were as follows: RISK-PCI (AUC=0.94; 95% CI 1.790-4.353), the GRACE score on admission (AUC=0.73; 95% CI 1.013-1.045), the GRACE score on discharge (AUC=0.65; 95% CI 0.999-1.033). The RISK-PCI score was the only score that could predict TVR (AUC=0.91; 95% CI 1.392-2.882). The RISK-PCI scoring system showed an excellent discriminative potential for 30-day death (AUC=0.96; 95% CI 1.339-3.548) in comparison with the GRACE scores on admission (AUC=0.88; 95% CI 1.018-1.072) and on discharge (AUC=0.78; 95% CI 1.000-1.058). In comparison with the GRACE and TIMI scores, RISK-PCI score showed a non-inferior ability to predict 30-day MACE and death in ACS patients. Moreover, RISK-PCI was the only scoring system that could predict recurrent ischemia requiring TVR.

  17. Comparison of RISK-PCI, GRACE, TIMI risk scores for prediction of major adverse cardiac events in patients with acute coronary syndrome

    PubMed Central

    Jakimov, Tamara; Mrdović, Igor; Filipović, Branka; Zdravković, Marija; Djoković, Aleksandra; Hinić, Saša; Milić, Nataša; Filipović, Branislav

    2017-01-01

    Aim To compare the prognostic performance of three major risk scoring systems including global registry for acute coronary events (GRACE), thrombolysis in myocardial infarction (TIMI), and prediction of 30-day major adverse cardiovascular events after primary percutaneous coronary intervention (RISK-PCI). Methods This single-center retrospective study involved 200 patients with acute coronary syndrome (ACS) who underwent invasive diagnostic approach, ie, coronary angiography and myocardial revascularization if appropriate, in the period from January 2014 to July 2014. The GRACE, TIMI, and RISK-PCI risk scores were compared for their predictive ability. The primary endpoint was a composite 30-day major adverse cardiovascular event (MACE), which included death, urgent target-vessel revascularization (TVR), stroke, and non-fatal recurrent myocardial infarction (REMI). Results The c-statistics of the tested scores for 30-day MACE or area under the receiver operating characteristic curve (AUC) with confidence intervals (CI) were as follows: RISK-PCI (AUC = 0.94; 95% CI 1.790-4.353), the GRACE score on admission (AUC = 0.73; 95% CI 1.013-1.045), the GRACE score on discharge (AUC = 0.65; 95% CI 0.999-1.033). The RISK-PCI score was the only score that could predict TVR (AUC = 0.91; 95% CI 1.392-2.882). The RISK-PCI scoring system showed an excellent discriminative potential for 30-day death (AUC = 0.96; 95% CI 1.339-3.548) in comparison with the GRACE scores on admission (AUC = 0.88; 95% CI 1.018-1.072) and on discharge (AUC = 0.78; 95% CI 1.000-1.058). Conclusions In comparison with the GRACE and TIMI scores, RISK-PCI score showed a non-inferior ability to predict 30-day MACE and death in ACS patients. Moreover, RISK-PCI was the only scoring system that could predict recurrent ischemia requiring TVR. PMID:29308832

  18. Elevation of Serum Acid Sphingomyelinase Activity in Acute Kawasaki Disease.

    PubMed

    Konno, Yuuki; Takahashi, Ikuko; Narita, Ayuko; Takeda, Osamu; Koizumi, Hiromi; Tamura, Masamichi; Kikuchi, Wataru; Komatsu, Akira; Tamura, Hiroaki; Tsuchida, Satoko; Noguchi, Atsuko; Takahashi, Tsutomu

    2015-10-01

    Kawasaki disease (KD) is an acute systemic vasculitis that affects both small and medium-sized vessels including the coronary arteries in infants and children. Acid sphingomyelinase (ASM) is a lysosomal glycoprotein that hydrolyzes sphingomyelin to ceramide, a lipid, that functions as a second messenger in the regulation of cell functions. ASM activation has been implicated in numerous cellular stress responses and is associated with cellular ASM secretion, either through alternative trafficking of the ASM precursor protein or by means of an unidentified mechanism. Elevation of serum ASM activity has been described in several human diseases, suggesting that patients with diseases involving vascular endothelial cells may exhibit a preferential elevation of serum ASM activity. As acute KD is characterized by systemic vasculitis that could affect vascular endothelial cells, the elevation of serum ASM activity should be considered in these patients. In the present study, serum ASM activity in the sera of 15 patients with acute KD was determined both before and after treatment with infusion of high-dose intravenous immunoglobulin (IVIG), a first-line treatment for acute KD. Serum ASM activity before IVIG was significantly elevated in KD patients when compared to the control group (3.85 ± 1.46 nmol/0.1 ml/6 h vs. 1.15 ± 0.10 nmol/0.1 ml/6 h, p < 0.001), suggesting that ASM activation may be involved in the pathophysiology of this condition. Serum ASM activity before IVIG was significantly correlated with levels of C-reactive protein (p < 0.05). These results suggest the involvement of sphingolipid metabolism in the pathophysiology of KD.

  19. Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease.

    PubMed

    Bowman, Louise; Hopewell, Jemma C; Chen, Fang; Wallendszus, Karl; Stevens, William; Collins, Rory; Wiviott, Stephen D; Cannon, Christopher P; Braunwald, Eugene; Sammons, Emily; Landray, Martin J

    2017-09-28

    Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. Among

  20. Adolescents with vascular frontal lesion: A neuropsychological follow up case study.

    PubMed

    Chávez, Clara L; Yáñez, Guillermina; Catroppa, Cathy; Rojas, Sulema; Escartin, Erick; Hearps, Stephen J C; García, Antonio

    2016-01-01

    The objective of this research was to identify clinically significant changes in cognitive functions in three adolescents who underwent surgery for resection of a focal vascular lesion in the frontal lobe. Cognitive functions, executive function, behavior regulation, emotion regulation, and social abilities were assessed prior to surgery, six and 24 months post-discharge. Significant clinical changes were observed during all the assessments. Cognitive changes after surgery are not homogeneous. Most of the significant clinical changes were improvements. Especially the significant clinical changes presented in EF domains were only improvements; these results suggest that EF were affected by the vascular lesion and benefitted by the surgery. After resection of a vascular lesion between 15 and 16 years of age the affected executive functions can continue the maturation process. Our results highlight the importance that assessments must include emotional aspects, even if deficits in these domains are not presented in the acute phase. Rehabilitation methods should promote the development of skills that help patients and their families to manage the emotional and behavioral changes that emerge once they are discharged from the hospital. Copyright © 2015 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.