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Sample records for acute vascular events

  1. Nilotinib-associated vascular events.

    PubMed

    Quintás-Cardama, Alfonso; Kantarjian, Hagop; Cortes, Jorge

    2012-10-01

    Anecdotal evidence suggests that nilotinib therapy may be associated with severe peripheral artery occlusive disease (PAOD). The authors describe the experience at M.D. Anderson Cancer Center regarding vascular events associated with nilotinib therapy in patients with chronic myeloid leukemia. Overall, 5 cases of PAOD were identified among 233 patients, for an incidence of 2%. Nilotinib is a highly selective inhibitor of the inactive conformation of ABL1 kinase. An improved topologic fit to the ABL1 protein-binding surface contributes to its increased potency over imatinib. This higher selectivity in vitro translated to an improved tolerability in vivo. In fact, nilotinib therapy in the frontline phase III ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients) study was associated with an improved toxicity profile compared with that of imatinib. Intriguingly, several cases of severe peripheral artery occlusive disease (PAOD) have been reported among patients treated with nilotinib in small series. We have identified 5 patients with chronic myeloid leukemia (CML) in whom vascular events developed that were likely related to nilotinib therapy among 233 (2%) patients treated at our institution: 1 patient had recurrent Raynaud syndrome, a second patient had recurrent cerebrovascular accidents, and 3 other patients had PAOD (2 of them with other vascular events, including coronary artery disease and pulmonary emboli, respectively). Risk factors for vascular disease were present in only 1 patient with a history of diabetes mellitus. Although the incidence of vascular events is low, this potential complication should be taken into account when selecting nilotinib for the treatment of CML.

  2. Challenges of targeting vascular stability in acute kidney injury.

    PubMed

    Basile, David P

    2008-08-01

    Acute kidney injury following folate administration is characterized by a vascular remodeling that is initially proliferative but subsequently results in vascular endothelial loss. Interventions directed toward promoting endothelial growth may preserve vascular structure and therefore renal function. However, angiopoietin-1 therapy in the setting of folate-induced acute kidney injury resulted in an expanded fibrotic response despite apparent preservation of the vasculature, indicating that renal repair responses are complex and vascular-directed therapies should be approached with caution.

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

    PubMed Central

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

    2015-01-01

    Background 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. Methods and Results 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. Conclusions 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. PMID:26251284

  4. Lymphatic Vascular Response to Acute Inflammation

    PubMed Central

    Lachance, Pier-Anne; Hazen, Amy; Sevick-Muraca, Eva M.

    2013-01-01

    During acute inflammation, functioning lymphatics are believed to reduce edema and to provide a transiting route for immune cells, but the extent at which the dermal lymphatic remodeling impacts lymphatic transport or the factors regulating these changes remains unclear. Herein we quantify the increase in lymphatic endothelial cells (LECs) and examine the expression of pro-angiogenenic and lymphangiogenic factors during acute cutaneous hypersensitivity (CHS). We found that LECs actively proliferate during CHS but that this proliferation does not affect the lymphatic vessel density. Instead, lymphatic remodeling is accompanied by lymphatic vessel leakiness and lower ejection of lymph fluid, which is observed only in the proximal lymphatic vessel draining the inflamed area. LECs and the immune cells release growth factors and cytokines during inflammation, which impact the lymphatic microenvironment and function. We identified that FGF-2, PLGF-2, HGF, EGF, and KC/CXCL17 are differentially expressed within tissues during acute CHS, but both VEGF-C and VEGF-D levels do not significantly change. Our results indicate that VEGF-C and VEGF-D are not the only players and other factors may be responsible for the LECs proliferation and altered lymphatic function in acute CHS. PMID:24086691

  5. Functional Integration of Acute Myeloid Leukemia into the Vascular Niche

    PubMed Central

    Leon, Ronald P.; Masri, Azzah Al; Clark, Hilary A.; Asbaghi, Steven A.; Tyner, Jeffrey W.; Dunlap, Jennifer; Fan, Guang; Kovacsovics, Tibor; Liu, Qiuying; Meacham, Amy; Hamlin, Kimberly L.; Hromas, Robert A.; Scott, Edward W.; Fleming, William H.

    2014-01-01

    Vascular endothelial cells are a critical component of the hematopoietic microenvironment that regulates blood cell production. Recent studies suggest the existence of functional cross-talk between hematologic malignancies and vascular endothelium. Here, we show that human acute myeloid leukemia (AML) localizes to the vasculature in both patients and in a xenograft model. A significant number of vascular tissue-associated AML cells (V-AML) integrate into vasculature in vivo and can fuse with endothelial cells. V-AML cells acquire several endothelial cell-like characteristics, including the up-regulation of CD105, a receptor associated with activated endothelium. Remarkably, endothelial-integrated V-AML shows an almost 4-fold reduction in proliferative activity compared to non-vascular associated AML. Primary AML cells can be induced to down regulate the expression of their hematopoietic markers in vitro and differentiate into phenotypically and functionally-defined endothelial-like cells. After transplantation, these leukemia-derived endothelial cells are capable of giving rise to AML. Taken together, these novel functional interactions between AML cells and normal endothelium along with the reversible endothelial cell potential of AML suggest that vascular endothelium may serve as a previously unrecognized reservoir for acute myeloid leukemia. PMID:24637335

  6. Acute management of vascular air embolism

    PubMed Central

    Shaikh, Nissar; Ummunisa, Firdous

    2009-01-01

    Vascular air embolism (VAE) is known since early nineteenth century. It is the entrainment of air or gas from operative field or other communications into the venous or arterial vasculature. Exact incidence of VAE is difficult to estimate. High risk surgeries for VAE are sitting position and posterior fossa neurosurgeries, cesarean section, laparoscopic, orthopedic, surgeries invasive procedures, pulmonary overpressure syndrome, and decompression syndrome. Risk factors for VAE are operative site 5 cm above the heart, creation of pressure gradient which will facilitate entry of air into the circulation, orogenital sex during pregnancy, rapid ascent in scuba (self contained underwater breathing apparatus) divers and barotrauma or chest trauma. Large bolus of air can lead to right ventricular air lock and immediate fatality. In up to 35% patient, the foramen ovale is patent which can cause paradoxical arterial air embolism. VAE affects cardiovascular, pulmonary and central nervous system. High index of clinical suspicion is must to diagnose VAE. The transesophgeal echocardiography is the most sensitive device which will detect smallest amount of air in the circulation. Treatment of VAE is to prevent further entrainment of air, reduce the volume of air entrained and haemodynamic support. Mortality of VAE ranges from 48 to 80%. VAE can be prevented significantly by proper positioning during surgery, optimal hydration, avoiding use of nitrous oxide, meticulous care during insertion, removal of central venous catheter, proper guidance, and training of scuba divers. PMID:20009308

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

    PubMed Central

    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. Images Figure 7 PMID:8866370

  8. 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.

  9. 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.

  10. Triple antiplatelet therapy for preventing vascular events: a systematic review and meta-analysis

    PubMed Central

    2010-01-01

    Background Dual antiplatelet therapy is usually superior to mono therapy in preventing recurrent vascular events (VEs). This systematic review assesses the safety and efficacy of triple antiplatelet therapy in comparison with dual therapy in reducing recurrent vascular events. Methods Completed randomized controlled trials investigating the effect of triple versus dual antiplatelet therapy in patients with ischaemic heart disease (IHD), cerebrovascular disease or peripheral vascular disease were identified using electronic bibliographic searches. Data were extracted on composite VEs, myocardial infarction (MI), stroke, death and bleeding and analysed with Cochrane Review Manager software. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using random effects models. Results Twenty-five completed randomized trials (17,383 patients with IHD) were included which involving the use of intravenous (iv) GP IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban), aspirin, clopidogrel and/or cilostazol. In comparison with aspirin-based therapy, triple therapy using an intravenous GP IIb/IIIa inhibitor significantly reduced composite VEs and MI in patients with non-ST elevation acute coronary syndromes (NSTE-ACS) (VE: OR 0.69, 95% CI 0.55-0.86; MI: OR 0.70, 95% CI 0.56-0.88) and ST elevation myocardial infarction (STEMI) (VE: OR 0.39, 95% CI 0.30-0.51; MI: OR 0.26, 95% CI 0.17-0.38). A significant reduction in death was also noted in STEMI patients treated with GP IIb/IIIa based triple therapy (OR 0.69, 95% CI 0.49-0.99). Increased minor bleeding was noted in STEMI and elective percutaneous coronary intervention (PCI) patients treated with GP IIb/IIIa based triple therapy. Stroke events were too infrequent for us to be able to identify meaningful trends and no data were available for patients recruited into trials on the basis of stroke or peripheral vascular disease. Conclusions Triple antiplatelet therapy based on iv GPIIb/IIIa inhibitors was more

  11. 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

  12. The prevalence of obesity-related hypertension and risk for new vascular events in patients with vascular diseases.

    PubMed

    Vernooij, Joris W P; van der Graaf, Yolanda; Visseren, Frank L J; Spiering, Wilko

    2012-10-01

    Higher body weight is associated with an increased prevalence of vascular risk factors. Obesity leads to hypertension by various mechanisms, often referred to as obesity-related hypertension. Aim of the present study was to evaluate the prevalence and the vascular risk of the combination of obesity and hypertension in patients with vascular diseases. A cohort of patients with various clinical manifest vascular diseases (n = 4,868) was screened for vascular risk factors and followed (median follow-up 4.2 years) for the occurrence of vascular events (stroke, myocardial infarction, and vascular death). The prevalence of obesity was 18% (95% confidence interval (CI) 17-19%) and the prevalence of hypertension was 83% (95% CI 82-84%). The prevalence of the combination of obesity and hypertension was 16% (95% CI 15-17%). Patients with high blood pressure (BP) combined with a high weight (highest tertile systolic BP (SBP) in the highest tertile BMI) were not at higher risk for new vascular events (hazard ratios (HR) 1.29; 95% CI 0.89-1.88) or mortality (HR 1.18; 95% CI 0.81-1.73) compared to patients without high BP and high weight (patients in the lowest tertile of SBP in the lowest tertile of BMI). Patients with only high weight did not have an elevated risk either for vascular events (HR 1.34; 95% CI 0.91-1.98) or mortality (HR 1.22; 95% CI 0.81-1.83) compared to patients without high BP and high weight. The prevalence of the combination of hypertension and obesity is low in patients with vascular diseases and does not confer a higher risk for recurrent vascular diseases and mortality than each risk factor alone.

  13. ACUTE MENTAL STRESS AND HEMOSTASIS: WHEN PHYSIOLOGY BECOMES VASCULAR HARM

    PubMed Central

    von Känel, Roland

    2015-01-01

    Stress-induced activation of the sympathoadrenal medullary system activates both the coagulation and fibrinolysis system resulting in net hypercoagulability. The evolutionary interpretation of this physiology is that stress-hypercoagulability protects a healthy organism from excess bleeding should injury occur in fight-or-flight situations. In turn, acute mental stress, negative emotions and psychological trauma also are triggering factors of atherothrombotic events and possibly of venous thromboembolism. Individuals with pre-existent atherosclerosis and impaired endothelial anticoagulant function are the most vulnerable to experience onset of acute coronary events within two hours of intense emotions. A range of sociodemographic and psychosocial factors (e.g., chronic stress and negative affect) might critically intensify and prolong stress-induced hypercoagulability. In contrast, several pharmacological compounds, dietary flavanoids, and positive affect mitigate the acute prothrombotic stress response. Studies are needed to investigate whether attenuation of stress-hypercoagulability through medications and biobehavioral interventions reduce the risk of thrombotic incidents in at-risk populations. PMID:25861135

  14. Factors influencing acute thrombus formation on carotid artery vascular grafts

    SciTech Connect

    Torem, S.; Schneider, P.A.; Paxton, L.D.; Yasuda, H.; Hanson, S.R.

    1988-10-01

    Scintillation camera imaging of 111Indium-labeled platelets has been used to measure acute thrombus formation on modified expanded Teflon (ePTFE) vascular grafts placed in the carotid arteries of normal baboons. Platelet deposition plateaued over 2 hr postoperatively and occurred primarily at the graft-vessel anastomoses. A positive correlation was found between the circulating platelet count in individual animals and the extent of early platelet thrombus deposition. Unmodified ePTFE grafts accumulated 4.6 +/- 1.2 x 10(9) platelets per graft, or 2.3 +/- 0.71 x 10(9) platelets per anastomosis. Acutely, platelet accumulation was reduced versus control graft results by coating the graft lumenal surfaces with a smooth layer of silicone rubber polymer (0.60 +/- 0.19 x 10(9) platelets per anastomosis; P less than 0.02) but not by coating the grafts using a plasma polymer based on methane, which did not modify graft texture (8.2 +/- 1.7 x 10(9) platelets per graft; P greater than 0.10). The benefit of the silicone rubber coating persisted for at least 48 hr. However, longer term patency was not preserved because 10 of 12 grafts placed had failed within 1 to 2 months.

  15. Endothelial Progenitor Cells Predict Cardiovascular Events after Atherothrombotic Stroke and Acute Myocardial Infarction. A PROCELL Substudy

    PubMed Central

    Cuadrado-Godia, Elisa; Regueiro, Ander; Núñez, Julio; Díaz-Ricard, Maribel; Novella, Susana; Oliveras, Anna; Valverde, Miguel A.; Marrugat, Jaume; Ois, Angel; Giralt-Steinhauer, Eva; Sanchís, Juan; Escolar, Ginès; Hermenegildo, Carlos; Roquer, Jaume

    2015-01-01

    Introduction The aim of this study was to determine prognostic factors for the risk of new vascular events during the first 6 months after acute myocardial infarction (AMI) or atherothrombotic stroke (AS). We were interested in the prognostic role of endothelial progenitor cells (EPC) and circulating endothelial cells (CEC) Methods Between February 2009 and July 2012, 100 AMI and 50 AS patients were consecutively studied in three Spanish centres. Patients with previously documented coronary artery disease or ischemic strokes were excluded. Samples were collected within 24h of onset of symptoms. EPC and CEC were studied using flow cytometry and categorized by quartiles. Patients were followed for up to 6 months. NVE was defined as new acute coronary syndrome, transient ischemic attack (TIA), stroke, or any hospitalization or death from cardiovascular causes. The variables included in the analysis included: vascular risk factors, carotid intima-media thickness (IMT), atherosclerotic burden and basal EPC and CEC count. Multivariate survival analysis was performed using Cox regression analysis. Results During follow-up, 19 patients (12.66%) had a new vascular event (5 strokes; 3 TIAs; 4 AMI; 6 hospitalizations; 1 death). Vascular events were associated with age (P = 0.039), carotid IMT≥0.9 (P = 0.044), and EPC count (P = 0.041) in the univariate analysis. Multivariate Cox regression analysis showed an independent association with EPC in the lowest quartile (HR: 10.33, 95%CI (1.22–87.34), P = 0.032] and IMT≥0.9 [HR: 4.12, 95%CI (1.21–13.95), P = 0.023]. Conclusions Basal EPC and IMT≥0.9 can predict future vascular events in patients with AMI and AS, but CEC count does not affect cardiovascular risk. PMID:26332322

  16. Keep off the grass: marijuana use and acute cardiovascular events.

    PubMed

    Caldicott, David G E; Holmes, James; Roberts-Thomson, Kurt C; Mahar, Leo

    2005-10-01

    Marijuana is one of the most widely used recreational substances in the world, considered by many consumers as a relatively safe drug with few significant side-effects. We report the case of a 21-year-old man who suffered an acute myocardial infarction following the use of marijuana, despite having no other identifiable risk factors for an acute cardiovascular event. We review the published medical literature regarding acute cardiovascular events following marijuana use and postulate a possible mechanism for this unusual pathological consequence of marijuana use.

  17. Extracellular Vesicle Proteins Associated with Systemic Vascular Events Correlate with Heart Failure: An Observational Study in a Dyspnoea Cohort

    PubMed Central

    Zhang, Ya-Nan; Vernooij, Flora; Ibrahim, Irwani; Ooi, Shirley; Gijsberts, Crystel M.; Schoneveld, Arjan H.; Sen, Kuan Win; den Ruijter, Hester M.; Timmers, Leo; Richards, Arthur Mark; Jong, Chun Tzen; Mazlan, Ibrahim; Wang, Jiong-Wei; Lam, Carolyn S. P.; de Kleijn, Dominique P. V.

    2016-01-01

    Background SerpinF2, SerpinG1, CystatinC and CD14 are involved in inflammatory processes and plasma extracellular vesicle (EV) -levels of these proteins have been reported to be associated with systemic vascular events. Evidence is accumulating that inflammatory processes may play a pivotal role both in systemic vascular events and in heart failure. Therefore, we studied the association between plasma extracellular vesicle SerpinF2-, SerpinG1-, CystatinC and CD14-levels and the occurrence of acute heart failure in patients. Methods and Result Extracellular vesicle protein levels of SerpinG1, SerpinF2, CystatinC and CD14 were measured in an observational study of 404 subjects presenting with dysponea at the emergency department (4B-cohort). Plasma extracellular vesicles were precipitated in a total extracellular vesicles (TEX)-fraction and in separate LDL- and HDL-subfractions. Extracellular vesicle protein levels were measured with a quantitative immune assay in all 3 precipitates. Out of 404 subjects, 141 (35%) were diagnosed with acutely decompensated heart failure. After correction for confounders (including comorbidities and medications), levels of CD14 in the HDL-fraction (OR 1.53, p = 0.01), SerpinF2 in the TEX-and LDL-fraction (ORs respectively 0.71 and 0.65, p<0.05) and SerpinG1 in the TEX-fraction (OR 1.55, p = 0.004) were statistically significantly related to heart failure. Furthermore, extracellular vesicle CD14- and SerpinF2-levels were significantly higher in heart failure patients with preserved ejection fraction than in those with reduced ejection fraction. Conclusion Extracellular vesicle levels of CD14, SerpinG1 and SerpinF2 are associated with the occurrence of heart failure in subjects suspected for acute heart failure, suggesting common underlying pathophysiological mechanisms for heart failure and vascular events. PMID:26820481

  18. Insight into 144 patients with ocular vascular events during VEGF antagonist injections

    PubMed Central

    Mansour, Ahmad M; Shahin, Maha; Kofoed, Peter K; Parodi, Maurizio B; Shami, Michel; Schwartz, Stephen G

    2012-01-01

    Aim To record ocular vascular events following injections of vascular endothelium growth factor (VEGF) antagonists. Methods Collaborative multicenter case series (48 cases), literature reviews (32 cases), and reports to the FDA (64 cases) of patients that had vascular occlusions during anti-VEGF therapy were collected and analyzed. Results A total of 144 cases of ocular vascular events were identified, with these diagnosed a median of 15 days after anti-VEGF injection. The majority of patients had pre-existing risk factors for cardiovascular events and nine patients had a prior history of glaucoma. Mean visual acuity dropped by 6.4 lines with severe visual loss after injection to NLP (five eyes), LP (six eyes), and HM (two eyes). The overall risk of ocular vascular events following a VEGF antagonist injection was 0.108% in the general population and 2.61% in the diabetic population. Mean retinal arterial constriction after intravitreal bevacizumab in 13 eyes was 21% (standard deviation = 27%), and mean retinal venous constriction was 8% (standard deviation = 30%). Conclusion Ocular vascular events are rare during anti-VEGF therapy, but can lead to severe visual loss and may be caused by a number of factors including the vasoconstrictor effect of the drug, a post-injection rise of intraocular pressure, patient stress as a result of the procedure, and the patient’s natural history of underlying ocular or systemic diseases. The diabetic population appears to have a tendency towards ocular vascular occlusions. PMID:22419856

  19. Haemostatic biomarkers are associated with long-term recurrent vascular events after ischaemic stroke.

    PubMed

    Pedersen, Annie; Redfors, Petra; Lundberg, Linnea; Gils, Ann; Declerck, Paul J; Nilsson, Staffan; Jood, Katarina; Jern, Christina

    2016-08-30

    Ischaemic stroke patients continue to be at risk for recurrent vascular events for many years. Predictors of long-term prognosis are needed. It was the objective of this study to investigate levels of four haemostatic proteins as long-term predictors of recurrent vascular events after ischaemic stroke. We prospectively followed 548 ischaemic stroke patients, 18-69 years, and registered recurrent vascular events. Plasma levels of tissue-type plasminogen activator (t-PA), von Willebrand factor (VWF), fibrinogen and thrombin activatable fibrinolysis inhibitor activation peptide (TAFI-AP) were measured three months after index stroke. Cox regression models were used to assess associations to outcomes for single biomarkers and for a combined biomarker measure. For single biomarkers significantly associated with any of the outcomes, we performed subanalyses stratified for age, sex, diabetes and atherosclerosis. During 5,637 person-years of follow-up, we registered 74 vascular deaths, 90 recurrent strokes and 62 coronary events. Levels of t-PA, VWF and fibrinogen were significantly associated with vascular death and coronary events. After adjustment, the association between t-PA and vascular death remained (HR per 1 SD increase in plasma level 1.27, 95 % CI 1.00-1.61, p=0.047). The combined effect of t-PA, VWF and fibrinogen was associated with coronary events (adjusted HR 1.35, 1.02-1.80, p=0.04). In non-diabetic patients, an association with coronary events was seen for VWF levels (adjusted HR 2.23, 1.45-3.43, p<0.01). In conclusion, plasma levels of haemostatic factors were associated with vascular death and coronary events, but not with recurrent stroke. Our results suggest that the predictive value of biomarkers differ by specific outcome measure and subgroup of patients.

  20. Factors Associated with Arterial Vascular Events in PROFILE: A Multiethnic Lupus Cohort

    PubMed Central

    Bertoli, Ana M.; Vilá, Luis M.; Alarcón, Graciela S.; McGwin, Gerald; Edberg, Jeffrey C.; Petri, Michelle; Ramsey-Goldman, Rosalind; Reveille, John D.; Kimberly, Robert P.

    2010-01-01

    Summary The objective of this study was to determine the factors associated with the occurrence of arterial vascular events in a multiethnic systemic lupus erythematosus (SLE) cohort. The PROFILE cohort, comprised of SLE patients (n=1,333) of defined ethnicity from five different U.S. institutions, was studied to determine demographic, clinical and biological variables associated with vascular events. An arterial vascular event (first episode) was either a myocardial infarction, angina pectoris and/or a vascular procedure for myocardial infarction, stroke, claudication and/or evidence of gangrene. Patient characteristics were analyzed by univariable and multivariable Cox proportional hazards regression analyses. One-hundred twenty-three (9.8%) patients had at least one incident arterial event. Age at cohort enrollment (HR= 1.04, 95% CI 1.03-1.06), smoking (HR= 2.20, 95% CI 1.40-3.46), and the CRP2* C alleles (HR= 1.91, 95%CI 1.04-3.49) were associated with a shorter time-to-the occurrence of arterial vascular events. Some clinical manifestations of disease activity were associated with a shorter time-to-occurrence [psychosis (HR= 2.21, 95% CI 1.10-4.44), seizures (HR= 1.85, 95% CI 1.00-3.24) and anemia (HR= 1.83, 95% CI 1.02-3.31)], but others were not [arthritis (HR= 0.32, 95% CI 0.18-0.58)]. In conclusion, older patients, especially in the context of a predisposing environmental factor (smoking) and severe clinical manifestations, are at higher risk of having arterial vascular events. The genetic contribution of the variation at the CRP locus was not obscured by demographic or clinical variables. Awareness of these factors should lead to more effective management strategies of patients at risk for arterial vascular events. PMID:19762396

  1. How data can help reduce vascular access events.

    PubMed

    Swails-Climer, Mary

    2012-11-01

    Thrombosis is the leading cause of access dysfunction and is expensive to treat. In 2011, only 10 AV access capable patients in our center were placed on a bridge catheter because of our ability to assess health and proactively use angioplasty to keep it open. Surveillance also helped us follow the progression of new fistula maturation and helped us decide on early intervention to prevent total, access failure. The Sparrow Center documented successful results with the selection of a new surveillance system that dramatically improved the quality of patient care and financial viability of the center. For dialysis center staffs looking for ways to operate more efficiently and at the same time reduce the incidence of vascular access complications caused by thrombosis, a data-driven surveillance device along with clinical monitoring protocols seems to provide a cost effective approach to addressing this critical area of patient care.

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

    SciTech Connect

    Ganaha, Fumikiyo; Yamada, Tetsuhisa; Yorozu, Naoya; Ujita, Masuo; Irie, Takeo; Fukuda, Yasushi; Fukuda, Kunihiko; Tada, Shimpei

    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.

  3. Association Between Vascular Access Dysfunction and Subsequent Major Adverse Cardiovascular Events in Patients on Hemodialysis

    PubMed Central

    Kuo, Te-Hui; Tseng, Chien-Tzu; Lin, Wei-Hung; Chao, Jo-Yen; Wang, Wei-Ming; Li, Chung-Yi; Wang, Ming-Cheng

    2015-01-01

    Abstract The association between dialysis vascular access dysfunction and the risk of developing major adverse cardiovascular events (MACE) in hemodialysis patients is unclear and has not yet been investigated. We analyzed data from the National Health Insurance Research Database of Taiwan to quantify this association. Adopting a case–control design nested within a cohort of patients who received hemodialysis from 2001 to 2010, we identified 9711 incident cases of MACE during the stage of stable maintenance dialysis and 19,422 randomly selected controls matched to cases on age, gender, and duration of dialysis. Events of vascular access dysfunction in the 6-month period before the date of MACE onset (ie, index date) for cases and before index dates for controls were evaluated retrospectively. The presence of vascular access dysfunction was associated with a 1.385-fold higher odds of developing MACE as estimated from the logistic regression analysis. This represents a significantly increased adjusted odds ratio (OR) at 1.268 (95% confidence interval [CI] = 1.186–1.355) after adjustment for comorbidities and calendar years of initiating dialysis. We also noted a significant exposure–response trend (P < 0.001) between the frequency of vascular access dysfunction and MACE, with the greatest risk (adjusted OR = 1.840, 95% CI = 1.549–2.186) noted in patients with ≥3 vascular access events. We concluded that dialysis vascular access dysfunction was significantly associated with an increased risk of MACE. Hence, vascular access failure can be an early sign for MACE in patients receiving maintenance hemodialysis. Active monitoring and treatment of cardiovascular risk factors and related diseases, not merely managing vascular access dysfunction, would be required to reduce the risk of MACE. PMID:26131808

  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. Long-term risk of vascular events after peripheral bypass surgery. A cohort study.

    PubMed

    Van Hattum, Eline S; Tangelder, Marco J D; Lawson, James A; Moll, Frans L; Algra, Ale

    2012-09-01

    Patients with peripheral arterial disease (PAD) are at high risk of major ischaemic events. Long-term data of all major ischaemic events in PAD patients are scarce and outdated, especially for patients with severe PAD requiring bypass surgery. Our objective was to define their long-term prognosis and develop a prediction model which quantifies this risk up to a decade after surgery. We conducted a retrospective cohort study in patients from the Dutch Bypass Oral anticoagulants or Aspirin (BOA) Study; a multicentre randomised trial comparing oral anticoagulants with aspirin after infrainguinal bypass surgery. The primary outcome was the composite event of non-fatal myocardial infarction, non-fatal ischaemic stroke, major amputation, and vascular death. Cumulative risks were assessed by Kaplan-Meier analysis and independent determinants by multivariable Cox regression models. From 1995 until 2009, 482 patients were followed for a median period of 7.8 years. Follow-up was complete in 94%. Overall 60% of patients experienced a primary outcome event, of which the majority was a vascular death (30%), followed by major amputations (12%). The primary cause of vascular death was a cardiovascular event (29%), whereas the minority was due to complications directly related to PAD (6%). Within five years after bypass surgery vascular death occurred in about a quarter of patients and within 10 years in nearly half of patients. This was double the rate as for non-vascular death. The primary outcome event occurred in over a third and over half of patients in 5 and 10 years after bypass surgery, respectively. From four independent determinants for the primary outcome event: age, diabetes, critical limb ischaemia, and prior vascular interventions, we developed a risk chart, which systematically classifies the 10-year risks of the primary outcome event, ranging from 25% to 85%. This study provided a detailed insight in the course of PAD long after peripheral bypass surgery and

  6. One of the most urgent vascular circumstances: Acute limb ischemia

    PubMed Central

    Sahin, Muslum; Kirma, Cevat

    2013-01-01

    Acute limb ischemia is a sudden decrease in limb perfusion that threatens limb viability and requires urgent evaluation and management. Most of the causes of acute limb ischemia are thrombosis of a limb artery or bypass graft, embolism from the heart or a disease artery, dissection, and trauma. Assessment determines whether the limb is viable or irreversibly damaged. Prompt diagnosis and revascularization by means of catheter-based thrombolysis or thrombectomy and by surgery reduce the risk of limb loss and mortality. Amputation is performed in patients with irreversible damage. Despite urgent revascularization, amputation rate is 10%–15% in patients during hospitalization, mostly above the knee, and mortality within 1 year is 10%–15% due to the coexisting conditions. PMID:26770694

  7. 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

    2016-01-01

    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. PMID:27594650

  8. Vascular stasis, intestinal hemorrhage, and heightened vascular permeability complicate acute portal hypertension in cd39-null mice

    PubMed Central

    Sun, Xiaofeng; Cárdenas, Andrés; Wu, Yan; Enjyoji, Keichi; Robson, Simon C.

    2009-01-01

    Vasoactive factors that regulate splanchnic hemodynamics include nitric oxide, catecholamines, and possibly extracellular nucleosides/nucleotides (adenosine, ATP). CD39/ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1) is the major vascular ectonucleotidase that hydrolyzes extracellular nucleotides. CD39 activity may be modulated by vascular injury, inflammation, and altered oxygen tension. Altered Cd39 expression by the murine hepatosplanchnic vasculature may impact hemodynamics and portal hypertension (PHT) in vivo. We noted that basal portal pressures (PPs) were comparable in wild-type and Cd39-null mice (n = 9). ATP infusions resulted in increments in PP in wild-type mice, but, in contrast, this significantly decreased in Cd39-null mice (n = 9) post-ATP in a nitric oxide-dependent manner. We then studied Cd39/NTPDase1 deletion in the regulation of portal hemodynamics, vascular integrity, and intestinal permeability in a murine model of PHT. Partial portal vein ligation (PPVL) was performed in Cd39-null (n = 44) and wild-type (n = 23) mice. Sequential measurements obtained after PPVL were indicative of comparable levels of PHT (ranges 14–29 mmHg) in both groups. There was one death in the wild-type group and eight in the Cd39-null group from intestinal bleeding (P = 0.024). Circulatory stasis in the absence of overt portal vein thrombosis, portal congestion, intestinal hemorrhage, and increased permeability were evident in all surviving Cd39-null mice. Deletion of Cd39 results in deleterious outcomes post-PPVL that are associated with significant microcirculatory derangements and major intestinal congestion with hemorrhage mimicking acute mesenteric occlusion. Absent Cd39/NTPDase1 and decreased generation of adenosine in the splanchnic circulation cause heightened vascular permeability and gastrointestinal hemorrhage in PPVL. PMID:19520738

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

    PubMed

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

    2013-03-15

    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

  10. Relationship between Kidney Dysfunction and Ischemic Stroke Outcomes: Albuminuria, but Not Estimated Glomerular Filtration Rate, Is Associated with the Risk of Further Vascular Events and Mortality after Stroke

    PubMed Central

    Lee, Dong-Geun

    2016-01-01

    Background and Objective Estimated glomerular filtration rate (eGFR) and albuminuria are known to be associated with ischemic stroke outcomes. In this study, we investigated the longitudinal relationships of the two markers with mortality, vascular events and functional outcomes in a stroke cohort. Methods A total of 295 patients with acute ischemic stroke were prospectively recruited in a single center between May 2012 and February 2015. Renal dysfunction was defined as a decreased eGFR (<60 mL/min/1.73 m2) or albuminuria (urine albumin-to-creatinine ratio ≥ 30 mg/g). Good functional outcome at 6 months was defined as a modified Rankin scale score ≤ 2, and the occurrence of major vascular events (stroke, acute coronary syndrome or peripheral artery occlusion) or death was monitored. The associations between renal dysfunction and mortality, major vascular events, and 6-month functional outcome were evaluated by the Cox proportional hazards model and logistic regression analysis. Unadjusted and adjusted hazards ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were obtained. A Kaplan–Meier survival curve for composite adverse events (major vascular events or death) was also computed according to the presence or absence of albuminuria. Results Albuminuria, not eGFR, was significantly associated with mortality (P = 0.028; HR 2.15; 95% CI 1.09–4.25) and major vascular events (P = 0.044; HR 2.24; 95% CI 1.02–4.94) in the multivariate Cox proportional hazards models adjusting for age, sex, diabetes, hypertension, current smoking, atrial fibrillation, previous stroke, alcohol history, initial National Institutes of Health Stroke Scale (NIHSS) score and eGFR. In addition, albuminuria was negatively associated with 6-month functional outcome in the multivariate logistic regression analysis adjusting for age, sex, diabetes, hypertension, current smoking, atrial fibrillation, previous stroke, alcohol history and eGFR (P = 0.001; OR 0.36; 95% CI 0

  11. A GAP in our knowledge of vascular signaling in acute kidney injury.

    PubMed

    Basile, David P

    2011-08-01

    Injury resulting from ischemia-reperfusion injury is a multifactorial process involving compromised function in both the tubular and the vascular compartments. Multiple vasoactive compounds have been implicated in the profound vasoconstriction that occurs in response to ischemia-reperfusion injury, and many of these factors signal through common G protein-coupled receptors. The report by Siedlecki et al. highlights the important roles of RGS4, a GTPase-accelerating protein (GAP), in the regulation of vascular tone in the setting of acute kidney injury.

  12. Acute respiratory distress syndrome caused by Mycoplasma pneumoniae without elevated pulmonary vascular permeability: a case report

    PubMed Central

    Takahashi, Naoki; Oi, Rie; Ota, Muneyuki; Toriumi, Shinichi; Ogushi, Fumitaka

    2016-01-01

    Sporadic patients with acute respiratory distress syndrome (ARDS) caused by Mycoplasma pneumoniae have been reported. However, knowledge about the pathophysiology and pharmacological treatment of this condition is insufficient. Moreover, the pulmonary vascular permeability in ARDS related to M. pneumoniae infection has not been reported. We report a case of ARDS caused by Mycoplasma pneumoniae without elevated pulmonary vascular permeability, which was successfully treated using low-dose short-term hydrocortisone, suggesting that pulmonary infiltration in ARDS caused by Mycoplasma pneumoniae does not match the criteria of permeability edema observed in typical ARDS. PMID:27162691

  13. Neuroprotection against vascular dementia after acupuncture combined with donepezil hydrochloride: P300 event related potential

    PubMed Central

    Liu, Qiang; Wang, Xiu-juan; Zhang, Zhe-cheng; Xue, Rong; Li, Ping; Li, Bo

    2016-01-01

    Acupuncture can be used to treat various nervous system diseases. Here, 168 vascular dementia patients were orally administered donepezil hydrochloride alone (5 mg/day, once a day for 56 days), or combined with acupuncture at Shenting (DU24), Tianzhu (BL10), Sishencong (Extra), Yintang (Extra), Renzhong (DU26), Neiguan (PC6), Shenmen (HT7), Fengchi (GB20), Wangu (GB12) and Baihui (DU20) (once a day for 56 days). Compared with donepezil hydrochloride alone, P300 event related potential latency was shorter with an increased amplitude in patients treated with donepezil hydrochloride and acupuncture. Mini-Mental State Examination score was also higher. Moreover, these differences in P300 latency were identified within different infarcted regions in patients treated with donepezil hydrochloride and acupuncture. These findings indicate that acupuncture combined with donepezil hydrochloride noticeably improves cognitive function in patients with vascular dementia, and exerts neuroprotective effects against vascular dementia. PMID:27127486

  14. CXCL12-producing vascular endothelial niches control acute T cell leukemia maintenance

    PubMed Central

    Pitt, Lauren A.; Tikhonova, Anastasia N.; Hu, Hai; Trimarchi, Thomas; King, Bryan; Gong, Yixiao; Sanchez-Martin, Marta; Tsirigos, Aris; Littman, Dan R.; Ferrando, Adolfo; Morrison, Sean J.; Fooksman, David R.

    2015-01-01

    SUMMARY The role of the microenvironment in T cell acute lymphoblastic leukemia (T-ALL), or any acute leukemia, is poorly understood. Here we demonstrate that T-ALL cells are in direct, stable contact with CXCL12-producing bone marrow stroma. Cxcl12 deletion from vascular endothelial, but not perivascular, cells impeded tumor growth, suggesting a vascular niche for T-ALL. Moreover, genetic targeting of CXCR4 in murine T-ALL after disease onset led to rapid, sustained disease remission, and CXCR4 antagonism suppressed human T-ALL in primary xenografts. Loss of CXCR4 targeted key T-ALL regulators, including the MYC pathway, and decreased leukemia initiating cell activity in vivo. Our data identify a T-ALL niche, and suggest targeting CXCL12/CXCR4 signaling as a powerful therapeutic approach for T-ALL. PMID:26058075

  15. Adaptive response of vascular endothelial cells to an acute increase in shear stress frequency

    PubMed Central

    Zhang, Ji

    2013-01-01

    Local shear stress sensed by arterial endothelial cells is occasionally altered by changes in global hemodynamic parameters, e.g., heart rate and blood flow rate, as a result of normal physiological events, such as exercise. In a recently study (41), we demonstrated that during the adaptive response to increased shear magnitude, porcine endothelial cells exhibited an unique phenotype featuring a transient increase in permeability and the upregulation of a set of anti-inflammatory and antioxidative genes. In the present study, we characterize the adaptive response of these cells to an increase in shear frequency, another important hemodynamic parameter with implications in atherogenesis. Endothelial cells were preconditioned by a basal-level sinusoidal shear stress of 15 ± 15 dyn/cm2 at 1 Hz, and the frequency was then elevated to 2 Hz. Endothelial permeability increased slowly after the frequency step-up, but the increase was relatively small. Using microarrays, we identified 37 genes that are sensitive to the frequency step-up. The acute increase in shear frequency upregulates a set of cell-cycle regulation and angiogenesis-related genes. The overall adaptive response to the increased frequency is distinctly different from that to a magnitude step-up. However, consistent with the previous study, our data support the notion that endothelial function during an adaptive response is different than that of fully adapted endothelial cells. Our studies may also provide insights into the beneficial effects of exercise on vascular health: transient increases in frequency may facilitate endothelial repair, whereas similar increases in shear magnitude may keep excessive inflammation and oxidative stress at bay. PMID:23851277

  16. Systemic vascular effects of acute electrical baroreflex stimulation.

    PubMed

    Burgoyne, Steven; Georgakopoulos, Dimitrios; Belenkie, Israel; Tyberg, John V

    2014-07-15

    We intended to determine if acute baroreflex activation therapy (BAT) increases venous capacitance and aortic conductance. BAT is effective in resistant hypertension, but its effect on the systemic vasculature is poorly understood. Left ventricular (LV) and aortic pressures and subdiaphragmatic aortic and caval flows (ultrasonic) were measured in six anesthetized dogs. Changes in abdominal blood volume (Vabdominal) were estimated as the integrated difference in abdominal aortic inflow and caval outflow. An electrode was implanted on the right carotid sinus. Data were measured during control and BAT. Next, sodium nitroprusside (SNP) was infused and BAT was subsequently added. Finally, angiotensin II (ANG II) was infused, and three increased BAT currents were added. We found that BAT decreased mean aortic pressure (PAo) by 22.5 ± 1.3 mmHg (P < 0.001) and increased aortic conductance by 16.2 ± 4.9% (P < 0.01) and Vabdominal at a rate of 2.2 ± 0.6 ml·kg(-1)·min(-1) (P < 0.01). SNP decreased PAo by 17.4 ± 0.7 mmHg (P < 0.001) and increased Vabdominal at a rate of 2.2 ± 0.7 ml·kg(-1)·min(-1) (P < 0.05). During the SNP infusion, BAT decreased PAo further, by 26.0 ± 2.1 mmHg (P < 0.001). ANG II increased PAo by 40.4 ± 3.5 mmHg (P = 0.001). When an increased BAT current was added, PAo decreased to baseline (P < 0.01) while aortic conductance increased from 62.3 ± 5.2% to 80.2 ± 3.3% (P < 0.05) of control. Vabdominal increased at a rate of 1.8 ± 0.9 ml·kg(-1)·min(-1) (P < 0.01), reversing the ANG II effects. In conclusion, BAT increases arterial conductance, decreases PAo, and increases venous capacitance even in the presence of powerful vasoactive drugs. Increasing venous capacitance may be an important effect of BAT in hypertension. PMID:24816258

  17. Acute exercise improves endothelial function despite increasing vascular resistance during stress in smokers and nonsmokers.

    PubMed

    Rooks, Cherie R; McCully, Kevin K; Dishman, Rod K

    2011-09-01

    The present study examined the effect of acute exercise on flow mediated dilation (FMD) and reactivity to neurovascular challenges among female smokers and nonsmokers. FMD was determined by arterial diameter, velocity, and blood flow measured by Doppler ultrasonography after forearm occlusion. Those measures and blood pressure and heart rate were also assessed in response to forehead cold and the Stroop Color-Word Conflict Test (CWT) before and after 30 min of rest or an acute bout of cycling exercise (∼50% VO₂ peak). Baseline FMD and stress responses were not different between smokers and nonsmokers. Compared to passive rest, exercise increased FMD and decreased arterial velocity and blood flow responses during the Stroop CWT and forehead cold in both groups. Overall, acute exercise improved endothelial function among smokers and nonsmokers despite increasing vascular resistance and reducing limb blood flow during neurovascular stress. PMID:21457274

  18. 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

  19. Stretching exercises enhance vascular endothelial function and improve peripheral circulation in patients with acute myocardial infarction.

    PubMed

    Hotta, Kazuki; Kamiya, Kentaro; Shimizu, Ryosuke; Yokoyama, Misako; Nakamura-Ogura, Misao; Tabata, Minoru; Kamekawa, Daisuke; Akiyama, Ayako; Kato, Michitaka; Noda, Chiharu; Matsunaga, Atsuhiko; Masuda, Takashi

    2013-01-01

    The purpose of this study was to clarify the acute effects of a single session of stretching exercises on vascular endothelial function and peripheral circulation in patients with acute myocardial infarction. This study evaluated 32 patients (mean age, 66 ± 9 years) who received phase I cardiac rehabilitation after acute myocardial infarction. Five types of stretching exercises were performed on the floor: wrist dorsiflexion, close-legged trunk flexion, open-legged trunk flexion, open-legged lateral trunk bending, and cross-legged trunk flexion. Each exercise entailed a 30-second stretching followed by a 30-second relaxation, and was repeated twice. Low- and high-frequency components (LF and HF) of heart rate variability (LF, 0.04-0.15 Hz; HF, 0.15-0.40 Hz) were analyzed, and HF and LF/HF were used as indices of parasympathetic and sympathetic nervous activities, respectively. Reactive hyperemia peripheral arterial tonometry (RH-PAT) index was measured and used as a parameter for vascular endothelial function. Transcutaneous oxygen pressure (tcPO2) on the right foot and chest was also measured, and the Foot-tcPO2/Chest-tcPO2 ratio was used as a parameter for peripheral circulation. The HF, RH-PAT index, and Foot-tcPO2/Chest-tcPO2 ratio were significantly higher after the exercises than before (P < 0.05, P < 0.01, and P < 0.05, respectively). There was no significant difference in the LF/HF ratio measured before and after stretching exercises. These findings demonstrate that stretching exercises improve vascular endothelial function and peripheral circulation in patients with acute myocardial infarction.

  20. 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.

  1. Mechanisms of vascular dysfunction in acute phase of Trypanosoma cruzi infection in mice.

    PubMed

    Silva, Josiane F; Capettini, Luciano S A; da Silva, José F P; Sales-Junior, Policarpo; Cruz, Jader Santos; Cortes, Steyner F; Lemos, Virginia S

    2016-07-01

    Vascular disorders have a direct link to mortality in the acute phase of Trypanosoma cruzi infection. However, the underlying mechanisms of vascular dysfunction in this phase are largely unknown. We hypothesize that T. cruzi invades endothelial cells causing dysfunction in contractility and relaxation of the mouse aorta. Immunodetection of T. cruzi antigen TcRBP28 was observed in endothelial cells. There was a decreased endothelial nitric oxide synthase (eNOS)-derived NO-dependent vascular relaxation, and increased vascular contractility accompanied by augmented superoxide anions production. Endothelial removal, inhibition of cyclooxygenase 2 (COX-2), blockade of thromboxane A2 (TXA2) TP receptors, and scavenger of superoxide normalized the contractile response. COX-2, thromboxane synthase, inducible nitric oxide synthase (iNOS), p65 NFκB subunit and p22(phox) of NAD(P)H oxidase (NOX) subunit expressions were increased in vessels of chagasic animals. Serum TNF-α was augmented. Basal NO production, and nitrotyrosine residue expression were increased. It is concluded that T. cruzi invades mice aorta endothelial cells and increases TXA2/TP receptor/NOX-derived superoxide formation. Alongside, T. cruzi promotes systemic TNF-α increase, which stimulates iNOS expression in vessels and nitrosative stress. In light of the heart failure that develops in the chronic phase of the disease, to understand the mechanism involved in the increased contractility of the aorta is crucial.

  2. Acute Changes in Peripheral Vascular Tonus and Systemic Circulation during Static Stretching.

    PubMed

    Inami, Takayuki; Baba, Reizo; Nakagaki, Akemi; Shimizu, Takuya

    2015-01-01

    This study aimed to investigate the acute effect of static stretching (SS) on peripheral vascular tonus and to clarify the effect of SS on systemic circulation. Twenty healthy young male volunteers performed a 1-min SS motion of the right triceps surae muscle, repeated five times. The peripheral vascular tonus (|d/a| ratio) was obtained using second derivatives of the photoplethysmogram readings before, during, and after SS. Heart rate and blood pressure (BP) were also measured. The |d/a| ratio and BP were transiently, but significantly, elevated during SS and returned to baseline immediately after SS. Furthermore, we observed a significant correlation between the amount of change in the |d/a| ratio and the ankle range of motion during SS (r = 0.793 to 0.832, P = 0.01). These responses may be caused by mechanical stress during SS.

  3. Cytoskeletal mechanisms regulating vascular endothelial barrier function in response to acute lung injury.

    PubMed

    Kása, Anita; Csortos, Csilla; Verin, Alexander D

    2015-01-01

    Endothelial cells (EC) form a semi-permeable barrier between the interior space of blood vessels and the underlying tissues. In acute lung injury (ALI) the EC barrier is weakened leading to increased vascular permeability. It is widely accepted that EC barrier integrity is critically dependent upon intact cytoskeletal structure and cell junctions. Edemagenic agonists, like thrombin or endotoxin lipopolysaccharide (LPS), induced cytoskeletal rearrangement, and EC contractile responses leading to disruption of intercellular contacts and EC permeability increase. The highly clinically-relevant cytoskeletal mechanisms of EC barrier dysfunction are currently under intense investigation and will be described and discussed in the current review. PMID:25838980

  4. Cytoskeletal mechanisms regulating vascular endothelial barrier function in response to acute lung injury

    PubMed Central

    Kása, Anita; Csortos, Csilla; Verin, Alexander D

    2014-01-01

    Endothelial cells (EC) form a semi-permeable barrier between the interior space of blood vessels and the underlying tissues. In acute lung injury (ALI) the EC barrier is weakened leading to increased vascular permeability. It is widely accepted that EC barrier integrity is critically dependent upon intact cytoskeletal structure and cell junctions. Edemagenic agonists, like thrombin or endotoxin lipopolysaccharide (LPS), induced cytoskeletal rearrangement, and EC contractile responses leading to disruption of intercellular contacts and EC permeability increase. The highly clinically-relevant cytoskeletal mechanisms of EC barrier dysfunction are currently under intense investigation and will be described and discussed in the current review. PMID:25838980

  5. Bioresorbable vascular scaffolds in patients with acute myocardial infarction: a new step forward to optimized reperfusion?

    PubMed Central

    Cuesta, Javier; Bastante, Teresa; Rivero, Fernando; García-Guimaraes, Marcos; Alvarado, Teresa; Benedicto, Amparo; Cortese, Bernardo; Byrne, Robert; Kastrati, Adnan

    2016-01-01

    Bioresorbable vascular scaffolds (BVS) represent a disruptive technology that has caused a new revolution in interventional cardiology. BVS appear to be particularly appealing in patients presenting with an acute myocardial infarction (MI). The available evidence on the value of BVS implantation in this challenging scenario is very promising but still limited. Results come from preliminary small observational studies, prospective registries that include a control group, and from scarce randomized clinical trials with surrogate mechanistic or angiographic primary end-points. Further studies, powered for clinical endpoints, are required to establish the relative safety and efficacy of BVS vs. new-generation metallic drug-eluting stents (DES) in patients with ST-segment elevation acute MI. PMID:27293870

  6. Current Trends in the Management of Acute Deep Vein Thrombosis among Korean Vascular Surgeons

    PubMed Central

    Kim, Kyeong-Sik; Kim, Dong-Ik

    2014-01-01

    Purpose: Venous thromboembolism (VTE) is a common life-threatening illness with significant morbidity and mortality rates. In recent years, the incidence of VTE has gradually increased in Korea. In this study, we evaluated the current trends in the management of acute deep vein thrombosis (DVT) in Korea. Materials and Methods: A 20-item questionnaire was prepared and sent to 48 members of the Korean Society for Vascular Surgery. Each member worked in a different hospital. Twenty-two members participated in this study. Results: The vascular surgery departments were primarily responsible for managing DVT. Ultrasound and computed tomography (CT) venography were chosen as the most common initial diagnostic tools. Eighty-two percent of participants routinely used the coagulation factor assay. Thrombolysis and inferior vena cava (IVC) filter insertion were performed mainly in the radiology departments. Seventy-seven percent of participants performed thrombolysis only if the thrombus age was less than 21 days. During thrombolysis, IVC filter was routinely inserted by 50% of respondents and removed within 14 days by 64% of respondents. Nearly all participants followed the 2012 American College of Chest Physicians guidelines for anticoagulation therapy. Conclusion: The majority of Korean vascular surgeons followed the guidelines. However, CT was frequently used. Thrombolysis and IVC filter insertion were more frequently performed than recommended by the guidelines. PMID:26217633

  7. Impaired endothelial proliferation and mesenchymal transition contribute to vascular rarefaction following acute kidney injury.

    PubMed

    Basile, David P; Friedrich, Jessica L; Spahic, Jasmina; Knipe, Nicole; Mang, Henry; Leonard, Ellen C; Changizi-Ashtiyani, Saeed; Bacallao, Robert L; Molitoris, Bruce A; Sutton, Timothy A

    2011-03-01

    Acute kidney injury induces the loss of renal microvessels, but the fate of endothelial cells and the mechanism of potential vascular endothelial growth factor (VEGF)-mediated protection is unknown. Cumulative cell proliferation was analyzed in the kidney of Sprague-Dawley rats following ischemia-reperfusion (I/R) injury by repetitive administration of BrdU (twice daily) and colocalization in endothelial cells with CD31 or cablin. Proliferating endothelial cells were undetectable for up to 2 days following I/R and accounted for only ∼1% of BrdU-positive cells after 7 days. VEGF-121 preserved vascular loss following I/R but did not affect proliferation of endothelial, perivascular cells or tubular cells. Endothelial mesenchymal transition states were identified by localizing endothelial markers (CD31, cablin, or infused tomato lectin) with the fibroblast marker S100A4. Such structures were prominent within 6 h and sustained for at least 7 days following I/R. A Tie-2-cre transgenic crossed with a yellow fluorescent protein (YFP) reporter mouse was used to trace the fate of endothelial cells and demonstrated interstititial expansion of YFP-positive cells colocalizing with S100A4 and smooth muscle actin following I/R. The interstitial expansion of YFP cells was attenuated by VEGF-121. Multiphoton imaging of transgenic mice revealed the alteration of YFP-positive vascular cells associated with blood vessels characterized by limited perfusion in vivo. Taken together, these data indicate that vascular dropout post-AKI results from endothelial phenotypic transition combined with an impaired regenerative capacity, which may contribute to progressive chronic kidney disease. PMID:21123492

  8. 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

  9. 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.

  10. 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

  11. Systems-level analysis of proteolytic events in increased vascular permeability and complement activation in skin inflammation.

    PubMed

    auf dem Keller, Ulrich; Prudova, Anna; Eckhard, Ulrich; Fingleton, Barbara; Overall, Christopher M

    2013-01-15

    During inflammation, vascular permeability is increased by various proteolytic events, such as the generation of bradykinin, that augment local tissue responses by enabling tissue penetration of serum proteins, including complement and acute-phase proteins. Proteases also govern inflammatory responses by processing extracellular matrix proteins and soluble bioactive mediators. We quantified changes in the proteome and the nature of protein amino termini (the N-terminome) and the altered abundance of murine proteases and inhibitors during skin inflammation. Through analysis of the N-terminome by iTRAQ-TAILS, we identified cotranslational and posttranslational αN-acetylation motifs, quantitative increases in protein abundance, and qualitative changes in the proteolytic signature during inflammation. Of the proteins identified in normal skin, about half were cleaved, and phorbol ester-induced inflammation increased the proportion of cleaved proteins, including chemokines and complement proteins, that were processed at previously uncharacterized sites. In response to phorbol ester-induced inflammation, mice deficient in matrix metalloproteinase 2 (MMP2) showed reduced accumulation of serum proteins in the skin and exhibited different proteolytic networks from those of wild-type mice. We found that the complement 1 (C1) inhibitor attenuated the increase in serum protein accumulation in inflamed skin. Cleavage and inactivation of the C1 inhibitor by MMP2 increased complement activation and bradykinin generation in wild-type mice, leading to increased vessel permeability during inflammation, which was diminished in Mmp2(-/-) mice. Thus, our systems-level analysis of proteolysis dissected cleavage events associated with skin inflammation and demonstrated that loss of a single protease could perturb the proteolytic signaling network and enhance inflammation.

  12. 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

  13. Time course of pulmonary vascular response to an acutely repetitive pulmonary microembolism in dogs--an analysis using pulmonary vascular impedance.

    PubMed

    Tobise, K; Tosaka, S; Onodera, S

    1992-05-01

    To understand the mechanism leading to progressive pulmonary hypertension, we investigated the time course of vascular response to an acutely repetitive pulmonary microembolism in dogs by using pulmonary vascular impedance. In a normal state, the mean pulmonary arterial pressure (mPAP) was transiently increased by emboli, and the impedance moduli of 0 Hz (= Rin), 1.5 Hz and 3 Hz were slightly increased. A four-element electrical vascular model showed the transient increase in peripheral pulmonary vascular resistance (R2) and inertia, and reduction in compliance (C). In contrast, in a state of a slight pulmonary hypertension, mPAP was continuously increased by the same amount of emboli, and the impedance moduli of both 0 Hz and 3 Hz were significantly increased. By a four-element model, a severe increase in R2 and reduction in C were observed, and these changes continued. Therefore, although the vascular response to pulmonary microembolism basically depends on the degree of mechanical obstruction, this response is thought to be modulated by the responsiveness of pulmonary vessels at that time, which is involved in the alteration in the local characteristics of pulmonary vessels, and/or the recruitment of a new blood flow.

  14. Involvement of Protein Kinase C-δ in Vascular Permeability in Acute Lung Injury.

    PubMed

    Ahn, Jong J; Jung, Jong P; Park, Soon E; Lee, Minhyun; Kwon, Byungsuk; Cho, Hong R

    2015-08-01

    Pulmonary edema is a major cause of mortality due to acute lung injury (ALI). The involvement of protein kinase C-δ (PKC-δ) in ALI has been a controversial topic. Here we investigated PKC-δ function in ALI using PKC-δ knockout (KO) mice and PKC inhibitors. Our results indicated that although the ability to produce proinflammatory mediators in response to LPS injury in PKC-δ KO mice was similar to that of control mice, they showed enhanced recruitment of neutrophils to the lung and more severe pulmonary edema. PKC-δ inhibition promoted barrier dysfunction in an endothelial cell layer in vitro, and administration of a PKC-δ-specific inhibitor significantly increased steady state vascular permeability. A neutrophil transmigration assay indicated that the PKC-δ inhibition increased neutrophil transmigration through an endothelial monolayer. This suggests that PKC-δ inhibition induces structural changes in endothelial cells, allowing extravasation of proteins and neutrophils.

  15. Small pulmonary vascular alteration and acute exacerbations of COPD: quantitative computed tomography analysis

    PubMed Central

    Wang, Zhiyue; Chen, Xuesong; Liu, Kouying; Xie, Weiping; Wang, Hong; Wei, Yongyue; Tang, Lijun; Zhu, Yinsu

    2016-01-01

    The morphologic alterations of pulmonary small vessels measured by computed tomography (CT) have been used to evaluate chronic obstructive pulmonary disease (COPD). However, the relationship between small pulmonary vascular alteration and acute exacerbations of COPD (AECOPD) is not well understood. The aim of this study was to evaluate the cross-sectional area (CSA) of small pulmonary vessel alterations measured on CT images and investigate its relationship with the COPD severity staged by the degree of airflow limitation and the occurrence of AECOPD. We retrospectively reviewed CT scans, clinical characteristics, and pulmonary function test results of 153 patients with COPD. All the patients were divided into AECOPD and non-AECOPD group according to the COPD staging and pulmonary function test results. The percentages of the total CSA less than 5 mm2 and equal to 5–10 mm2 over the lung area (%CSA<5 and %CSA5–10, respectively) were measured. The %CSA<5 steadily decreased in relation to the increase of COPD severity. In addition, %CSA<5 of the AECOPD group was significantly lower than that of the non-AECOPD group (0.41±0.13 versus 0.68±0.18, P<0.001), and the optimal cutoff value was 0.56 (sensitivity, 0.863; specificity, 0.731). Therefore, small pulmonary vascular alteration, as measured by %CSA<5, could indicate not only the degree of COPD severity, but also the occurrence of AECOPD. PMID:27578971

  16. Adrenoceptor hyporeactivity is responsible for Escherichia coli endotoxin-induced acute vascular dysfunction in humans.

    PubMed

    Pleiner, Johannes; Heere-Ress, Elisabeth; Langenberger, Herbert; Sieder, Anna E; Bayerle-Eder, Michaela; Mittermayer, Fritz; Fuchsjäger-Mayrl, Gabriele; Böhm, Johannes; Jansen, Burkhard; Wolzt, Michael

    2002-01-01

    Impaired response to catecholamines contributes to the altered hemodynamics in sepsis, which has been attributed to excessive NO formation. We have studied the systemic hemodynamic and local forearm responses and inducible NO synthase (iNOS) expression during experimental endotoxemia in humans. Escherichia coli endotoxin (lipopolysaccharide [LPS]) was administered at doses of 1 or 2 ng/kg to healthy volunteers. In 10 subjects, the systemic pressor effect of phenylephrine was assessed before and after the administration of LPS. In 9 further subjects, forearm blood flow responses to intra-arterial noradrenaline, acetylcholine, glyceryl trinitrate, and N(G)-monomethyl-L-arginine (L-NMMA) were studied at baseline and after LPS administration. Peripheral blood was collected and analyzed for iNOS mRNA and protein. Four hours after LPS, the response of systolic blood pressure (P<0.0005) and heart rate (P<0.05) to phenylephrine was significantly reduced. In the forearm, noradrenaline-induced vasoconstriction was also reduced by approximately 50% (P<0.01), but L-NMMA responsiveness was unchanged. iNOS mRNA or protein was not increased. Marked vascular adrenoceptor hyporeactivity is detectable in the absence of increased NO activity or iNOS expression in endotoxemia, arguing against major involvement of vascular iNOS activity in the acute systemic vasodilation to LPS.

  17. Small pulmonary vascular alteration and acute exacerbations of COPD: quantitative computed tomography analysis.

    PubMed

    Wang, Zhiyue; Chen, Xuesong; Liu, Kouying; Xie, Weiping; Wang, Hong; Wei, Yongyue; Tang, Lijun; Zhu, Yinsu

    2016-01-01

    The morphologic alterations of pulmonary small vessels measured by computed tomography (CT) have been used to evaluate chronic obstructive pulmonary disease (COPD). However, the relationship between small pulmonary vascular alteration and acute exacerbations of COPD (AECOPD) is not well understood. The aim of this study was to evaluate the cross-sectional area (CSA) of small pulmonary vessel alterations measured on CT images and investigate its relationship with the COPD severity staged by the degree of airflow limitation and the occurrence of AECOPD. We retrospectively reviewed CT scans, clinical characteristics, and pulmonary function test results of 153 patients with COPD. All the patients were divided into AECOPD and non-AECOPD group according to the COPD staging and pulmonary function test results. The percentages of the total CSA less than 5 mm(2) and equal to 5-10 mm(2) over the lung area (%CSA<5 and %CSA5-10, respectively) were measured. The %CSA<5 steadily decreased in relation to the increase of COPD severity. In addition, %CSA<5 of the AECOPD group was significantly lower than that of the non-AECOPD group (0.41±0.13 versus 0.68±0.18, P<0.001), and the optimal cutoff value was 0.56 (sensitivity, 0.863; specificity, 0.731). Therefore, small pulmonary vascular alteration, as measured by %CSA<5, could indicate not only the degree of COPD severity, but also the occurrence of AECOPD. PMID:27578971

  18. Vascular Pathology in the Extracranial Vertebral Arteries in Patients with Acute Ischemic Stroke

    PubMed Central

    Bentsen, L.; Nygård, A.; Ovesen, C.; Christensen, A.; Rosenbaum, S.; Havsteen, I.; Christensen, H.

    2014-01-01

    Introduction Vascular pathology in the extracranial vertebral arteries remains among the possible causes in cryptogenic stroke. However, the diagnosis is challenged by the great variety in the anatomy of the vertebral arteries, clinical symptoms and difficulties in the radiological assessments. The aim of this study was to assess the prevalence of CT angiography (CTA)-detected pathological findings in the extracranial vertebral arteries in an acute stroke population and secondly to determine the frequency of posterior pathology as probable cause in patients with otherwise cryptogenic stroke. Method The analysis was based on 657 consecutive patients with symptoms of acute stroke and a final diagnosis of ischemic stroke or transient ischemic attack. On admission, a noncontrast CT cerebrum and CTA were performed. A senior consultant neuroradiologist, blinded to clinical data, reviewed all CTA scans systematically, assessing the four segments of the extracranial vertebral arteries. First, the frequency of pathological findings including stenosis, plaques, dissection, kinked artery and coiling was assessed. Subsequently, we explored the extent of the pathological findings that were the most plausible causes of stroke, namely either a possible dissection or a kinked artery. Results Findings in the extracranial vertebral arteries included significant stenosis (0.8%), atherosclerotic plaque types (3.8%), possible dissections (2.6%), kinked arteries (2.6%) and coiling (32.0%). Eighteen patients (2.8%) with pathological findings had an unknown cause of stroke, likely posterior symptoms and no clinical stroke symptoms from the anterior circuit. Of these, 3 cases were kinked arteries (0.5%) and 15 cases (2.3%) were possible dissections. Conclusion We found that in approximately 3% of the study population, the most plausible cause of the cryptogenic strokes was due to a pathological finding in the posterior extracranial vertebral arteries, being either a possible dissection or

  19. 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…

  20. Endovascular Acute Stroke Treatment Performed by Vascular Interventional Radiologists: Is It Safe and Efficacious?

    SciTech Connect

    Fjetland, Lars Roy, Sumit; Kurz, Kathinka D.; Larsen, Jan Petter; Kurz, Martin W.

    2012-10-15

    Purpose: To evaluate the safety and efficacy of neurointerventional procedures in acute stroke patients performed by a team of vascular interventional radiologists in close cooperation with diagnostic neuroradiologists and stroke neurologists and to compare the results with those of previous reports from centres with specialised interventional neuroradiologists. Material and Methods: A total of 39 patients with acute ischemic stroke due to large-vessel occlusion not responding to or not eligible for intravenous thrombolysis were treated with either intra-arterial thrombolysis or mechanical thrombectomy (Penumbra System or solitaire FR thrombectomy system, respectively) and included in our prospective study. Outcomes were measured using the modified Rankin scale after 90 days, and recanalization was assessed by thrombolysis using the myocardial infarction score. Results: Mean patient age was 68.3 {+-} 14.2 years; the average National Institutes of Health Stroke Scale score at hospital admission was 17.2 (SD = 6.2 [n = 38]). Successful recanalization was achieved in 74.4 % of patients. Median time from clinical onset to recanalization was 5 h 11 min. Procedure-related complications occurred in 5 % of patients, and 7.5 % had a symptomatic intracerebral hemorrhage. Of the patients, 22.5 % died within the first 90 postprocedural days, 5 % of these from cerebral causes. Patients who were successfully recanalized had a clinical better outcome at follow-up than those in whom treatment failed. Of the patients, 35.9 % had an mRS score {<=}2 after 90 days. Conclusion: Our results are in line with those in the published literature and show that a treatment strategy with general interventional radiologists performing neurointerventional procedures in acute stroke patients with large vessel occlusions can be achieved to the benefit of patients.

  1. 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.

  2. [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. PMID:26047152

  3. Correlation between vascular endothelial growth factor and long-term prognosis in patients with acute myocardial infarction

    PubMed Central

    NIU, JIAMIN; HAN, XIA; QI, HUAXIN; YIN, JIE; ZHANG, ZHIQIANG; ZHANG, ZENGTANG

    2016-01-01

    The aim of the present study was to investigate the correlation between plasma the levels of vascular endothelial growth factor (VEGF) and major adverse cardiovascular events (MACE) in patients with acute myocardial infarction (AMI). A total of 124 patients with AMI undergoing emergency percutaneous coronary intervention (PCI) were selected, and plasma VEGF levels were measured 7 days after the onset of AMI using an enzyme-linked immunosorbent assay. The patients were divided into the L (≤190 pg/ml VEGF) and H (>190 pg/ml VEGF) groups, and were followed up every 2 months for an average of 12 months. MACE were recorded during follow-up. On the basis of these results, the patients were further divided into the MACE and non-MACE (N-MACE) groups, and the serum VEGF concentration was compared between the two groups. At the 6-month follow-up, the incidence of MACE in the H group was found to be significantly reduced compared with the L group. The serum VEGF concentration in the N-MACE group was significantly higher compared with the MACE group. Multinomial logistic regression revealed that reduced VEGF levels (β=1.243; 95% CI, 1.018–1.326; P=0.026) were independent risk factors for MACE. In conclusion, high plasma VEGF levels at 7 days after AMI onset facilitate the long-term prognosis in the same infarct zone in patients with AMI, while low plasma VEGF levels are independent risk factors for MACE. PMID:27347081

  4. 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. PMID:23861167

  5. Metabolic Syndrome Is a Strong Risk Factor for Minor Ischemic Stroke and Subsequent Vascular Events

    PubMed Central

    Wang, Guang-Sheng; Tong, Dao-Ming; Chen, Xiao-Dong; Yang, Tong-Hui; Zhou, Ye-Ting; Ma, Xiao-Bo

    2016-01-01

    Background Minor ischemic stroke (MIS) represents a major global public health problem worldwide due to high incidence. The aim of this study was to investigate whether metabolic syndrome (MetS) is a strong risk for MIS and subsequent vascular events (SVE). Methods A retrospective cohort study was performed examining symptomatic MIS in a Chinese neurologic outpatient population aged over 25 years without history of stroke. MetS was defined using the International Diabetes Federation criteria. MIS was diagnosed by magnetic resonance imaging-diffusion weighted images or fluid-attenuated inversion recovery. Results Of 1361 outpatients, a total of 753 (55.3%) patients were diagnosed with MIS; of them, 80% had a score of 0 using the MIS had a 0 score on the National Institutes of Health Stroke Scale. Among these, 303 (40.2%) individuals with MIS were diagnosed with MetS. Diagnosed of MIS with MetS significantly correlated with abdominal obesity (30.7% v.s 18.0%), hypertension (91.1% v.s 81.6%), increased blood glucose (6.9±2.4 v.s 5.0±0.4), dyslipidemia (78.2% v.s 48.2%), and SVE (50.5% v.s 11.3%) when compared with the controls group. On adjusted analysis, the risk of SVE was also significantly associated with three additional MetS criterion (RR,9.0; 95% CI, 5.677–14.46). Using Cox proportional analysis, risk of SVE in patient with MIS was significantly associated with MetS (RR, 3.3; 95% CI, 1.799–6.210), older age (RR, 1.0; 95% CI, 1.001–1.048), and high blood glucose (RR,1.1; 95%CI, 1.007–1.187). Conclusions The MetS is a strong risk factor for MIS, and patients presenting with MIS and MetS are at a high risk of SVE. Further studies are required to determine the improvement of Mets prevention in the reduction of MIS and SVE. PMID:27536865

  6. 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

    2015-08-01

    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.

  7. 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.

  8. Acute effects of an oral nitric oxide supplement on blood pressure, endothelial function, and vascular compliance in hypertensive patients.

    PubMed

    Houston, Mark; Hays, Laurie

    2014-07-01

    This blinded placebo-controlled crossover study evaluated the acute effects of an orally disintegrating lozenge that generates nitric oxide (NO) in the oral cavity on blood pressure (BP) response, endothelial function, and vascular compliance in unmedicated hypertensive patients. Thirty patients with clinical hypertension were recruited and enrolled in a blinded placebo-controlled clinical trial in an outpatient setting. Average baseline BP in 30 patients was 144±3/91±1 mm Hg. NO supplementation resulted in a significant decrease of 4 mm Hg in resting systolic BP (P<.003) and a significant decrease of 5 mm Hg in diastolic BP (P<.002) from baseline and placebo after 20 minutes. In addition, there was a further statistically significant reduction by 6 mm Hg in both systolic and diastolic pressure after 60 minutes (P<.0001 vs baseline). After a half hour of a single dose, there was a significant improvement in vascular compliance as measured by augmentation index and, after 4 hours, a statistically significant improvement in endothelial function as measured by the EndoPAT (Itamar Medical, Franklin, MA). A single administration of an oral active NO supplement appears to acutely lower BP, improve vascular compliance, and restore endothelial function in patients with hypertension. PMID:24962851

  9. Duration of Diabetes Predicts Aortic Pulse Wave Velocity and Vascular Events in Alström Syndrome

    PubMed Central

    Smith, Jamie; Carey, Catherine; Barrett, Timothy; Campbell, Fiona; Maffei, Pietro; Marshall, Jan D.; Paisey, Christopher; Steeds, Richard P.; Edwards, Nicola C.; Bunce, Susan; Geberhiwot, Tarekegn

    2015-01-01

    Context: Alström syndrome is characterized by increased risk of cardiovascular disease from childhood. Objective: To explore the association between risk factors for cardiovascular disease, aortic pulse wave velocity, and vascular events in Alström syndrome. Design: Cross-sectional analyses with 5-year follow-up. Setting: The UK NHS nationally commissioned specialist clinics for Alström syndrome. Patients: Thirty-one Alström patients undertook vascular risk assessment, cardiac studies, and aortic pulse wave velocity measurement. Subsequent clinical outcomes were recorded. Interventions: Insulin resistance was treated with lifestyle intervention and metformin, and diabetes with the addition of glitazones, glucagon-like peptide 1 agonists, and/or insulin. Thyroid and T deficiencies were corrected. Dyslipidemia was treated with statins and nicotinic acid derivatives. Cardiomyopathy was treated with standard therapy as required. Main Outcome Measures: The associations of age, gender, and risk factors for cardiovascular disease with aortic pulse wave velocity were assessed and correlated with the effects of reduction in left ventricular function. Vascular events were monitored for 5 years. Results: Aortic pulse wave velocity was positively associated with the duration of diabetes (P = .001) and inversely with left ventricular ejection fraction (P = .036). Five of the cohort with cardiovascular events had higher aortic pulse wave velocity (P = .0247), and all had long duration of diabetes. Conclusions: Duration of diabetes predicted aortic pulse wave velocity in Alström syndrome, which in turn predicted cardiovascular events. This offers hope of secondary prevention because type 2 diabetes can be delayed or reversed by lifestyle interventions. PMID:26066530

  10. Effects of Cinacalcet on Atherosclerotic and Nonatherosclerotic Cardiovascular Events in Patients Receiving Hemodialysis: The EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial

    PubMed Central

    Wheeler, David C.; London, Gerard M.; Parfrey, Patrick S.; Block, Geoffrey A.; Correa‐Rotter, Ricardo; Dehmel, Bastian; Drüeke, Tilman B.; Floege, Jürgen; Kubo, Yumi; Mahaffey, Kenneth W.; Goodman, William G.; Moe, Sharon M.; Trotman, Marie‐Louise; Abdalla, Safa; Chertow, Glenn M.; Herzog, Charles A.

    2014-01-01

    Background Premature cardiovascular disease limits the duration and quality of life on long‐term hemodialysis. The objective of this study was to define the frequency of fatal and nonfatal cardiovascular events attributable to atherosclerotic and nonatherosclerotic mechanisms, risk factors for these events, and the effects of cinacalcet, using adjudicated data collected during the EValuation of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial. Methods and Results EVOLVE was a randomized, double‐blind, placebo‐controlled clinical trial that randomized 3883 hemodialysis patients with moderate to severe secondary hyperparathyroidism to cinacalcet or matched placebo for up to 64 months. For this post hoc analysis, the outcome measure was fatal and nonfatal cardiovascular events reflecting atherosclerotic and nonatherosclerotic cardiovascular diseases. During the trial, 1518 patients experienced an adjudicated cardiovascular event, including 958 attributable to nonatherosclerotic disease. Of 1421 deaths during the trial, 768 (54%) were due to cardiovascular disease. Sudden death was the most frequent fatal cardiovascular event, accounting for 24.5% of overall mortality. Combining fatal and nonfatal cardiovascular events, randomization to cinacalcet reduced the rates of sudden death and heart failure. Patients randomized to cinacalcet experienced fewer nonatherosclerotic cardiovascular events (adjusted relative hazard 0.84, 95% CI 0.74 to 0.96), while the effect of cinacalcet on atherosclerotic events did not reach statistical significance. Conclusions Accepting the limitations of post hoc analysis, any benefits of cinacalcet on cardiovascular disease in the context of hemodialysis may result from attenuation of nonatherosclerotic processes. Clinical Trials Registration Unique identifier: NCT00345839. URL: ClinicalTrials.gov. PMID:25404192

  11. High hyperdiploid childhood acute lymphoblastic leukemia: Chromosomal gains as the main driver event.

    PubMed

    Paulsson, Kajsa

    2016-01-01

    High hyperdiploid childhood acute lymphoblastic leukemia is characterized by multiple chromosomal gains. Recent results show that this subtype harbors relatively few genetic abnormalities besides the extra chromosomes, which appear to arise early and are likely the main driver event. Secondary hits primarily target genes in the rat sarcoma (RAS) signaling pathway and histone modifiers. PMID:27308574

  12. Vascular Immunotargeting of Glucose Oxidase to the Endothelial Antigens Induces Distinct Forms of Oxidant Acute Lung Injury

    PubMed Central

    Christofidou-Solomidou, Melpo; Kennel, Stephen; Scherpereel, Arnaud; Wiewrodt, Rainer; Solomides, Charalambos C.; Pietra, Giuseppe G.; Murciano, Juan-Carlos; Shah, Sayed A.; Ischiropoulos, Harry; Albelda, Steven M.; Muzykantov, Vladimir R.

    2002-01-01

    Oxidative endothelial stress, leukocyte transmigration, and pulmonary thrombosis are important pathological factors in acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Vascular immunotargeting of the H2O2-generating enzyme glucose oxidase (GOX) to the pulmonary endothelium causes an acute oxidative lung injury in mice. 1 In the present study we compared the pulmonary thrombosis and leukocyte transmigration caused by GOX targeting to the endothelial antigens platelet-endothelial cell adhesion molecule (PECAM) and thrombomodulin (TM). Both anti-PECAM and anti-TM delivered similar amounts of 125I-GOX to the lungs and caused a dose-dependent, tissue-selective lung injury manifested within 2 to 4 hours by high lethality, vascular congestion, polymorphonuclear neutrophil (PMN) sequestration in the pulmonary vasculature, severe pulmonary edema, and tissue oxidation, yet at an equal dose, anti-TM/GOX inflicted more severe lung injury than anti-PECAM/GOX. Moreover, anti-TM/GOX-induced injury was accompanied by PMN transmigration in the alveolar space, whereas anti-PECAM/GOX-induced injury was accompanied by PMN degranulation within vascular lumen without PMN transmigration, likely because of PECAM blockage. Anti-TM/GOX caused markedly more severe pulmonary thrombosis than anti-PECAM/GOX, likely because of TM inhibition. These results indicate that blocking of specific endothelial antigens by GOX immunotargeting modulates important pathological features of the lung injury initiated by local generation of H2O2 and that this approach provides specific and robust models of diverse variants of human ALI/ARDS in mice. In particular, anti-TM/GOX causes lung injury combining oxidative, prothrombotic, and inflammatory components characteristic of the complex pathological picture seen in human ALI/ARDS. PMID:11891211

  13. Primary prevention with lipid lowering drugs and long term risk of vascular events in older people: population based cohort study

    PubMed Central

    Alpérovitch, Annick; Kurth, Tobias; Bertrand, Marion; Ancelin, Marie-Laure; Helmer, Catherine; Debette, Stéphanie

    2015-01-01

    Objective To determine the association between use of lipid lowering drugs (statin or fibrate) in older people with no known history of vascular events and long term risk of coronary heart disease and stroke Design Ongoing prospective population based cohort study recruited in 1999-2000, with five face-to-face examinations. Setting Random sample of community dwelling population aged 65 years and over, living in three French cities (Bordeaux, Dijon, Montpellier). Participants 7484 men and women (63%) with mean age 73.9 years and no known history of vascular events at entry. Mean follow-up was 9.1 years. Main outcome measures Adjusted hazard ratios of coronary heart disease and stroke in baseline lipid lowering drug users compared with non-users, calculated using multivariable Cox proportional hazard models adjusted for numerous potential confounding factors. Hazard ratios were estimated for use of any lipid lowering drug and for statin and fibrate separately. Results Lipid lowering drug users were at decreased risk of stroke compared with non-users (hazard ratio 0.66, 95% confidence interval 0.49 to 0.90); hazard ratios for stroke were similar for statin (0.68, 0.45 to1.01) and fibrate (0.66, 0.44 to 0.98). No association was found between lipid lowering drug use and coronary heart disease (hazard ratio 1.12, 0.90 to 1.40). Analyses stratified by age, sex, body mass index, hypertension, systolic blood pressure, triglyceride concentrations, and propensity score did not show any effect modification by these variables, either for stroke or for coronary heart disease. Conclusion In a population based cohort of older people with no history of vascular events, use of statins or fibrates was associated with a 30% decrease in the incidence of stroke. PMID:25989805

  14. Diagnostic ramifications of ocular vascular occlusion as a first thrombotic event associated with factor V Leiden and prothrombin gene heterozygosity

    PubMed Central

    Schockman, Samantha; Glueck, Charles J; Hutchins, Robert K; Patel, Jaykumar; Shah, Parth; Wang, Ping

    2015-01-01

    Aim This study aimed to assess the diagnostic ramifications of vascular occlusion of the ocular vein and artery as a first thrombotic event associated with factor V Leiden (FVL) and/or prothrombin gene (PTG) heterozygosity. Methods Patients with ocular vein (n=191) and artery (n=74) occlusion, free of cardioembolic etiologies, were sequentially referred from vitreoretinal specialists for measurement of thrombophilia-hypofibrinolysis and compared to 110 healthy normal controls. Results Of the 265 patients, 29 (11%; 17 women, 12 men) of all referred ocular vascular occlusion (OVO) cases were found to be heterozygous for FVL and/or PTG, including 16 with FVL, 12 with PTG, and 1 with both. Of the 29 cases, 16 had central retinal vein occlusion (CRVO), 2 branch retinal vein occlusion (BRVO), 5 nonarteritic anterior ischemic optic neuropathy (NA-AION), 3 retinal artery occlusion (RAO), 2 amaurosis fugax (AF), and 1 had both CRVO and RAO. Of the 16 FVL cases, 15 (94%) had OVO as a first thrombotic event without prior deep venous thrombosis (DVT) or pulmonary embolism (PE); 6 (38%) also had other thrombotic events, including recurrent miscarriage, osteonecrosis, ischemic stroke, and/or ischemic colitis; and 5 (31%) had immediate family members with previous venous thromboembolism (VTE). Of the 12 PTG cases, 9 (75%) had OVO as a first thrombotic event, 5 (42%) experienced VTE other than DVT or PE, and 6 (50%) had immediate family members with VTE. In one patient with both FVL and PTG, DVT occurred before BRVO. Of the 17 women with FVL and/or PTG mutations, 7 (41%) experienced ≥1 miscarriage, 6 (35%) were on estrogen therapy, and 1 (6%) was on clomiphene. Conclusion Of the 265 patients with OVO, 29 (11%) had FVL and/or PTG, and 83% of these 29 cases presented with OVO as their first thrombotic event. By diagnosing thrombophilia as an etiology for OVO, the ophthalmologist opens a window to family screening and preventive therapy. PMID:25897198

  15. Vascular Risk Factors and Diseases Modulate Deficits of Reward-Based Reversal Learning in Acute Basal Ganglia Stroke

    PubMed Central

    Wicking, Manon; Bellebaum, Christian; Hermann, Dirk M.

    2016-01-01

    Background Besides motor function, the basal ganglia have been implicated in feedback learning. In patients with chronic basal ganglia infarcts, deficits in reward-based reversal learning have previously been described. Methods We re-examined the acquisition and reversal of stimulus-stimulus-reward associations and acquired equivalence in eleven patients with acute basal ganglia stroke (8 men, 3 women; 57.8±13.3 years), whose performance was compared eleven healthy subjects of comparable age, sex distribution and education, who were recruited outside the hospital. Eleven hospitalized patients with a similar vascular risk profile as the stroke patients but without stroke history served as clinical control group. Results In a neuropsychological assessment 7±3 days post-stroke, verbal and spatial short-term and working memory and inhibition control did not differ between groups. Compared with healthy subjects, control patients with vascular risk factors exhibited significantly reduced performance in the reversal phase (F[2,30] = 3.47; p = 0.044; post-hoc comparison between risk factor controls and healthy controls: p = 0.030), but not the acquisition phase (F[2,30] = 1.01; p = 0.376) and the acquired equivalence (F[2,30] = 1.04; p = 0.367) tasks. In all tasks, the performance of vascular risk factor patients closely resembled that of basal ganglia stroke patients. Correlation studies revealed a significant association of the number of vascular risk factors with reversal learning (r = -0.33, p = 0.012), but not acquisition learning (r = -0.20, p = 0.121) or acquired equivalence (r = -0.22, p = 0.096). Conclusions The previously reported impairment of reward-based learning may be attributed to vascular risk factors and associated diseases, which are enriched in stroke patients. This study emphasizes the necessity of appropriate control subjects in cognition studies. PMID:27163585

  16. Prognostic value of intravenous dipyridamole thallium scintigraphy after an acute myocardial ischemic event

    SciTech Connect

    Younis, L.T.; Byers, S.; Shaw, L.; Barth, G.; Goodgold, H.; Chaitman, B.R.

    1989-07-15

    Seventy-seven patients recovering from an acute coronary event were studied by intravenous dipyridamole thallium scintigraphy to evaluate the prognostic value and safety of the test in this patient subset. Forty-four patients (58%) had unstable angina and 33 (42%) had an acute myocardial infarction. One death occurred within 24 hours of testing. Sixty-eight patients were followed for an average of 12 months; 25, 31 and 23% had a fixed, reversible or combined thallium defect on their predischarge thallium scan. During follow-up, 10 patients died or had a nonfatal myocardial infarction; in each case, a reversible or combined myocardial thallium defect was present. Univariate analysis of 17 clinical, scintigraphic and angiographic variables showed that a reversible thallium defect and the angiographically determined extent of coronary artery disease were predictors of future cardiac events. The extent of coronary disease and global left ventricular ejection fraction were predictors of subsequent reinfarction or death. Logistic regression analyses revealed that a reversible thallium defect (p less than 0.001) and the extent of coronary disease (p less than 0.009) were the only significant predictors of a cardiac event. When death or reinfarction were the outcome variables, the extent of coronary disease (p less than 0.02) and left ventricular ejection fraction (p less than 0.06) were the only variables selected. Thus, intravenous dipyridamole thallium scintigraphy after an acute coronary ischemic syndrome is a useful and relatively safe noninvasive test to predict subsequent cardiac events.

  17. 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

  18. The effect of acute administration of Vitamin D on micro vascular endothelial function in Caucasians and South Asian Indians

    PubMed Central

    Petrofsky, Jerrold; Alshammari, Faris; Khowailed, Iman Akef; Rodrigues, Sophia; Potnis, Pooja; Akerkar, Siddhesh; Shah, Jinal; Chung, Guyeon; Save, Rakhi

    2013-01-01

    Background Vitamin D is a modulator of the immune system. There is some limited evidence that it also increases local blood flow in response to stress. Material/Methods In the present study, we examined 20 age matched subjects; 10 whom were from India and 10 Caucasians from the United States. Subjects were administered 4000 IU of Vitamin D3 for 3 weeks at breakfast. The function of the endothelial cells was evaluated in 2 ways; first, the response to 4 minutes of vascular occlusion was measured with a laser Doppler flow meter and second, the blood flow response to local heat at 42°C for 6 minutes. Results The results of the experiments showed that, as reported previously, the endothelial function in people from India was less than their Caucasian counterparts. The blood flow response to heat was reduced after 3 weeks administration of vitamin D in both groups and the response to vascular occlusion in the Caucasian group. But there was only a 20% reduction in the blood flow response to heat in the Caucasian group and a 50% reduction in the group from India. Conclusions Thus acute doses of vitamin D may increase vascular tone and reduce blood flow to tissue during stressors. Dosages administered for a longer duration may have beneficial effects on endothelial function but this was not examined here. PMID:23917403

  19. PEDF improves cardiac function in rats with acute myocardial infarction via inhibiting vascular permeability and cardiomyocyte apoptosis.

    PubMed

    Zhang, Hao; Wang, Zheng; Feng, Shou-Jie; Xu, Lei; Shi, He-Xian; Chen, Li-Li; Yuan, Guang-Da; Yan, Wei; Zhuang, Wei; Zhang, Yi-Qian; Zhang, Zhong-Ming; Dong, Hong-Yan

    2015-03-11

    Pigment epithelium-derived factor (PEDF) is a pleiotropic gene with anti-inflammatory, antioxidant and anti-angiogenic properties. However, recent reports about the effects of PEDF on cardiomyocytes are controversial, and it is not known whether and how PEDF acts to inhibit hypoxic or ischemic endothelial injury in the heart. In the present study, adult Sprague-Dawley rat models of acute myocardial infarction (AMI) were surgically established. PEDF-small interfering RNA (siRNA)-lentivirus (PEDF-RNAi-LV) or PEDF-LV was delivered into the myocardium along the infarct border to knockdown or overexpress PEDF, respectively. Vascular permeability, cardiomyocyte apoptosis, myocardial infarct size and animal cardiac function were analyzed. We also evaluated PEDF's effect on the suppression of the endothelial permeability and cardiomyocyte apoptosis under hypoxia in vitro. The results indicated that PEDF significantly suppressed the vascular permeability and inhibited hypoxia-induced endothelial permeability through PPARγ-dependent tight junction (TJ) production. PEDF protected cardiomyocytes against ischemia or hypoxia-induced cell apoptosis both in vivo and in vitro via preventing the activation of caspase-3. We also found that PEDF significantly reduced myocardial infarct size and enhanced cardiac function in rats with AMI. These data suggest that PEDF could protect cardiac function from ischemic injury, at least by means of reducing vascular permeability, cardiomyocyte apoptosis and myocardial infarct size.

  20. Acute effects of vascular modifying agents in solid tumors assessed by noninvasive laser Doppler flowmetry and near infrared spectroscopy.

    PubMed

    Kragh, Michael; Quistorff, Bjørn; Horsman, Michael R; Kristjansen, Paul E G

    2002-01-01

    The potential of noninvasive laser Doppler flowmetry (LDF) and near infrared spectroscopy (NIRS) to detect acute effects of different vascular-modifying agents on perfusion and blood volume in tumors was evaluated. C3H mouse mammary carcinomas (approximately 200 mm(3)) in the rear foot of CDF1 mice were treated with flavone acetic acid (FAA, 150 mg/kg), 5,6-dimethylxanthenone-4-acetic acid (DMXAA, 20 mg/kg), combretastatin A-4 disodium phosphate (CA4DP, 250 mg/kg), hydralazine (HDZ, 5 mg/kg), or nicotinamide (NTA, 500 mg/kg). Tumor perfusion before and after treatment was evaluated by noninvasive LDF, using a 41 degrees C heated custom-built LDF probe with four integrated laser/receiver units, and tumor blood volume was estimated by NIRS, using light guide coupled reflectance measurements at 800+/-10 nm. FAA, DMXAA, CA4DP, and HDZ significantly decreased tumor perfusion by 50%, 47%, 73%, and 78%, respectively. In addition, FAA, DMXAA, and HDZ significantly reduced the blood volume within the tumor, indicating that these compounds to some degree shunted blood from the tumor to adjacent tissue, HDZ being most potent. CA4DP caused no change in the tumor blood volume, indicating that the mechanism of action of CA4DP was vascular shut down with the blood pool trapped in the tumor. NTA caused no change in either tumor perfusion or tumor blood volume. We conclude that noninvasive LDF and NIRS can determine acute effects of vascular modifying agents on tumor perfusion and blood volume.

  1. PCB 77 dechlorination products modulate pro-inflammatory events in vascular endothelial cells.

    PubMed

    Eske, Katryn; Newsome, Bradley; Han, Sung Gu; Murphy, Margaret; Bhattacharyya, Dibakar; Hennig, Bernhard

    2014-05-01

    Persistent organic pollutants such as polychlorinated biphenyls (PCBs) are associated with detrimental health outcomes including cardiovascular diseases. Remediation of these compounds is a critical component of environmental policy. Although remediation efforts aim to completely remove toxicants, little is known about the effects of potential remediation byproducts. We previously published that Fe/Pd nanoparticles effectively dechlorinate PCB 77 to biphenyl, thus eliminating PCB-induced endothelial dysfunction using primary vascular endothelial cells. Herein, we analyzed the toxic effects of PCB congener mixtures (representative mixtures of commercial PCBs based on previous dechlorination data) produced at multiple time points during the dechlorination of PCB 77 to biphenyl. Compared with pure PCB 77, exposing endothelial cells to lower chlorinated PCB byproducts led to improved cellular viability, decreased superoxide production, and decreased nuclear factor kappa B activation based on duration of remediation. Presence of the parent compound, PCB 77, led to significant increases in mRNA and protein inflammatory marker expression. These data implicate that PCB dechlorination reduces biological toxicity to vascular endothelial cells.

  2. Rho-Associated Kinase Activity Is an Independent Predictor of Cardiovascular Events in Acute Coronary Syndrome

    PubMed Central

    Kajikawa, Masato; Noma, Kensuke; Nakashima, Ayumu; Maruhashi, Tatsuya; Iwamoto, Yumiko; Matsumoto, Takeshi; Iwamoto, Akimichi; Oda, Nozomu; Hidaka, Takayuki; Kihara, Yasuki; Aibara, Yoshiki; Chayama, Kazuaki; Sasaki, Shota; Kato, Masaya; Dote, Keigo; Goto, Chikara; Liao, James K.; Higashi, Yukihito

    2016-01-01

    Rho-associated kinases play an important role in a variety of cellular functions. Although Rho-associated kinase activity has been shown to be an independent predictor for future cardiovascular events in a general population, there is no information on Rho-associated kinase activity in patients with acute coronary syndrome. We evaluated leukocyte Rho-associated kinase activity by Western blot analysis in 73 patients with acute coronary syndrome and 73 age- and gender-matched control subjects. Rho-associated kinase activity within 2 hours of acute coronary syndrome onset was higher in patients with acute coronary syndrome than in the control subjects (0.95±0.55 versus 0.69±0.31; P<0.001). Rho-associated kinase activity promptly increased from 0.95±0.55 to 1.11±0.81 after 3 hours and reached a peak of 1.21±0.76 after 1 day (P=0.03 and P=0.03, respectively) and then gradually decreased to 0.83±0.52 after 7 days, 0.78±0.42 after 14 days, and 0.72±0.30 after 6 months (P=0.22, P=0.29, and P=0.12, respectively). During a median follow-up period of 50.8 months, 31 first major cardiovascular events (death from cardiovascular causes, myocardial infarction, ischemic stroke, and coronary revascularization) occurred. After adjustment for age, sex, cardiovascular risk factors, and concomitant treatment with statins, increased Rho-associated kinase activity was associated with increasing risk of first major cardiovascular events (hazard ratio, 4.56; 95% confidence interval, 1.98–11.34; P<0.001). These findings suggest that Rho-associated kinase activity is dramatically changed after acute coronary syndrome and that Rho-associated kinase activity could be a useful biomarker to predict cardiovascular events in Japanese patients with acute coronary syndrome. PMID:26283039

  3. Inflammatory Cytokines as Risk Factors for Mortality After Acute Cardiac Events

    PubMed Central

    Hamzic-Mehmedbasic, Aida

    2016-01-01

    Introduction: Inflammatory markers have been identified as potential indicators of future adverse outcome after acute cardiac events. Aim: This study aimed to analyze baseline inflammatory cytokines levels in patients with acute heart failure (AHF) and/or acute coronary syndrome (ACS) according to survival. The main objective was to identify risk factors for mortality after an episode of AHF and/or ACS. Methods: In this prospective longitudinal study 75 patients with the diagnosis of AHF and/or ACS were enrolled. Baseline laboratory and clinical data were retrieved. Serum and urine interleukin-6 (IL-6) and interleukin-18 (IL-18) levels, plasma B-type natriuretic peptide (BNP) and serum cystatin C values were determined. The primary outcome was in-hospital mortality while secondary outcome was six-month mortality. Results: Median serum and urine IL-6 levels, serum and urine IL-18 levels, as well as median concentrations of plasma BNP and serum cystatin C, were significantly increased in deceased in comparison to surviving AHF and/or ACS patients. Univariate Cox regression analysis identified serum IL-6, serum IL-18, urine IL-6, urine IL-18 as well as serum cystatin C and Acute Physiology and Chronic Health Evaluation (APACHE) II score as risk factors for mortality after an episode of AHF and/or ACS. Multivariate Cox regression analysis revealed that only serum IL-6 is the independent risk factor for mortality after acute cardiac events (HR 61.7, 95% CI 2.1-1851.0; p=0.018). Conclusion: Present study demonstrated the strong prognostic value of serum IL-6 in predicting mortality of patients with AHF and/or ACS. PMID:27703283

  4. Safety Events in Kidney Transplant Recipients: Results from the Folic Acid for Vascular Outcome Reduction in Transplant (FAVORIT) Trial

    PubMed Central

    Weir, Matthew R.; Gravens-Muller, Lisa; Costa, Nadiesda; Ivanova, Anastasia; Manitpisitkul, Wana; Bostom, Andrew G.; Diamantidis, Clarissa J.

    2015-01-01

    Background Kidney transplant recipients are at increased risk for adverse safety events related to their reduced renal function and many medications. Methods We determined the incidence of adverse safety events based on previously defined Agency for Healthcare and Research Quality (AHRQ) ICD-9 code-derived patient safety indicators (PSI) in the Folic Acid for Vascular Outcome Reduction in Transplant (FAVORIT) trial participants who had a hospitalization stratified by tertiles of estimated glomerular filtration rate. We also examined the frequency of Micromedex defined two precautionary drug-drug interactions, and two medications whose use may be contraindicated due to reduced GFR from the FAVORIT trial Medication Thesaurus at baseline, and annually among 4110 participants. Logistic regression was used to examine the relationship between patient safety events and baseline demographic and clinical variables at a participant level. Event rates were estimated at participant and visit levels. Results Of the 2514 patients with a hospitalization, 978 (38.9%) experienced an AHRQ PSI. Factors which were associated with more common AHRQ PSI included: US location, history of cardiovascular disease or diabetes, and lower tertile of estimated GFR. At a participant level, 2524 of the 4110 participants (61.4%) were taking a CNI and a statin, 378 (9.2%) were taking azathioprine and an ACE inhibitor, 171 (12.9%) were taking a sulfonylurea ), 45 (3.4%) were taking metformin despite a baseline GFR below 40 ml/min/1.73m2. Conclusions We conclude that patient safety events are not uncommon in kidney transplant recipients. Careful monitoring is necessary to prevent adverse outcomes. PMID:25393158

  5. Detection of acute synthetic vascular graft infection with In-labeled leukocyte scanning: an animal study

    SciTech Connect

    Dries, D.J.; Alazraki, N.; Lawrence, P.F.; Murphy, K.M.; Kercher, J.; Datz, F.L.; Christian, P.; Taylor, A. Jr.

    1985-11-01

    Synthetic vascular graft infection is characterized by late diagnosis due to indolent and nonspecific symptoms. Indium- -labeled leukocyte imaging holds promise as a diagnostic tool to identify vascular graft infection, but reported data on its accuracy are somewhat sparse and conflicting. In this study, 13 mongrel dogs received Dacron aortic interposition grafts. Seven grafts were contaminated at the time of surgery by topical ATCC Staphylococcus aureus concentrated at 10(8) organisms/ml. Six control animals received no graft contamination. All infected animals were sacrificed on the second postoperative day after In leukocyte scanning. The results showed a sensitivity of 71%, specificity of 100%, and accuracy of 85% for the 111In leukocyte study in detecting early graft infections; false-positive leukocyte scans in the early postoperative period were not a problem as has been reported by others. These data indicate that leukocyte scanning for graft infection detection is likely to be clinically valuable.

  6. Using Discrete Event Computer Simulation to Improve Patient Flow in a Ghanaian Acute Care Hospital

    PubMed Central

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

    2014-01-01

    Objectives Crowding and limited resources have increased the strain on acute care facilities and emergency departments (EDs) worldwide. These problems are particularly prevalent in developing countries. Discrete event simulation (DES) is a computer-based tool that can be used to estimate how changes to complex healthcare delivery systems, such as EDs, 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. Methods We developed a simulation model of acute care at a district level hospital in Ghana to test the effects of resource-neutral (e.g. modified staff start times and roles) and resource-additional (e.g. increased staff) operational interventions on patient throughput. Previously captured, de-identified 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). Results The base-case (no change) scenario had a mean LOS of 292 minutes (95% CI 291, 293). In isolation, neither adding staffing, changing staff roles, nor varying shift times affected overall patient LOS. Specifically, adding two registration workers, history takers, and physicians resulted in a 23.8 (95% CI 22.3, 25.3) minute 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). Conclusions Resource-neutral interventions identified through DES modeling have the potential to improve acute care throughput in this Ghanaian municipal hospital. DES offers another approach to identifying potentially effective interventions to improve patient flow in emergency and acute

  7. 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.

  8. Effects of competition on acute phase proteins and lymphocyte subpopulations - oxidative stress markers in eventing horses.

    PubMed

    Valle, E; Zanatta, R; Odetti, P; Traverso, N; Furfaro, A; Bergero, D; Badino, P; Girardi, C; Miniscalco, B; Bergagna, S; Tarantola, M; Intorre, L; Odore, R

    2015-10-01

    The aim of the study was to evaluate markers of the acute phase response (APR) in eventing horses by measuring acute phase proteins (APP) (haptoglobin, Hp, and serum amyloid A, SAA), lysozyme, protein adducts such as pentosidine-like adducts (PENT), malondialdehyde adducts (MDA), hydroxynonenal adducts (HNE) and total advanced glycation/glycoxidation end products (AGEs), complete blood count and lymphocyte subpopulations (CD4+, CD8+ and CD21+) both at rest and at the end of an eventing competition. Blood samples were collected from eight Warmblood horses (medium age 10 ± 3) during an official national 2-day event competition at rest (R) and 10 min after the arrival of the cross-country test on the second day. Exercise caused a significant increase in red blood cell number, haemoglobin, packed cell volume, neutrophils, white blood cell and lymphocyte number; however, these values remained within the normal range. The CD4+ and CD8+ cells significantly increased, whereas the CD21+ lymphocytes decreased; a significant increase in serum SAA, lysozyme and protein carbonyl derivates was also observed. Two-day event causes significant changes in APR markers such as lysozyme, protein carbonyl derivates (HNE, AGEs, PENT) and lymphocyte subpopulations. The data support the hypothesis that 2-day event may alter significantly APR markers. Limitations of the study were the relatively small sample size and sampling time conditioned by the official regulations of the event. Therefore, further studies are needed to investigate the time required for recovery to basal values in order to define the possible effects on the immune function of the athlete horse.

  9. Renal and Cardiac Endothelial Heterogeneity Impact Acute Vascular Rejection in Pig-to-Baboon Xenotransplantation

    PubMed Central

    Knosalla, C.; Yazawa, K.; Behdad, A.; Bodyak, N.; Shang, H.; Bühler, L.; Houser, S.; Gollackner, B.; Griesemer, A.; Schmitt-Knosalla, I.; Schuurman, H.-J.; Awwad, M.; Sachs, D. H.; Cooper, D. K. C.; Yamada, K.; Usheva, A.; Robson, S. C.

    2010-01-01

    Xenograft outcomes are dictated by xenoantigen expression, for example, Gal α 1, 3Gal (Gal), but might also depend on differing vascular responses. We investigated whether differential vascular gene expression in kidney and cardiac xenografts correlate with development of thrombotic microangiopathy (TM) and consumptive coagulation (CC). Immunosuppressed baboons underwent miniswine or hDAF pig kidney (n = 6) or heart (n = 7), or Gal-transferase gene-knockout (GalT-KO) (thymo)kidney transplantation (n = 14). Porcine cDNA miniarrays determined donor proinflammatory, apoptosis-related and vascular coagulant/fibrinolytic gene expression at defined time points; validated by mRNA, protein levels and immunopathology. hDAF-transgenic and GalT-KO xenografts, (particularly thymokidneys) exhibited prolonged survival. CC was seen with Gal-expressing porcine kidneys (3 of 6), only 1 of 7 baboons post-cardiac xenotransplantation and was infrequent following GalT-KO grafts (1 of 14). Protective-type genes (heme oxygenase-I, superoxide dismutases and CD39) together with von Willebrand factor and P-selectin were upregulated in all renal grafts. Transcriptional responses in Gal-expressing xenografts were comparable to those seen in the infrequent GalT-KO rejection. In cardiac xenografts, fibrin deposition was associated with increased plasminogen activator inhibitor-1 expression establishing that gene expression profiles in renal and cardiac xenografts differ in a quantitative manner. These findings suggest that therapeutic targets may differ for renal and cardiac xenotransplants. PMID:19422330

  10. Lessons learned from study of depression in cardiovascular patients in an acute-care heart and vascular hospital.

    PubMed

    Davis, Michael; Brennan, J Michael; Vish, Nancy; Adams, Jenny; Muldoon, Mary; Renbarger, Tara; Garner, John

    2013-01-01

    Depression is highly prevalent in patients with cardiovascular disease, but questions about the effectiveness of screening and intervention remain unanswered. To evaluate the effects of proactive intervention at an acute-care heart and vascular hospital, patients who reported depressive symptoms on admission were randomized to an active, counseling-based depression intervention plus standard care (referral to a primary or psychiatric care physician) or to standard care alone. Despite early termination of patient enrollment because of lower-than-expected recruitment rates, the project had a positive impact. By involving and educating staff, the investigators raised awareness and improved the process of identifying and helping depressed patients. The lessons in study design and execution gained from this experience will help ensure success in future studies of this condition.

  11. Abdominal aortic occlusion and vascular compromise secondary to acute gastric dilatation in a patient with bulimia.

    PubMed

    Elsharif, M; Doulias, T; Aljundi, W; Balchandra, S

    2014-11-01

    Acute gastric dilation is a rare but recognised complication in patients with bulimia and anorexia following binge episodes owing to decreased bowel motility. We present a rare case of acute gastric dilation secondary to bulimia in an otherwise healthy 18-year-old female patient that resulted in compression and complete occlusion of the abdominal aorta, leading to acute mesenteric and bilateral lower limb ischaemia. This resolved immediately following a laparotomy and gastric decompression. Management of these patients is very challenging owing to the lack of a successful precedent. To our knowledge, such a catastrophic complication has only ever been reported once in the literature and the outcome was fatal. Our case is of additional importance as it offers a successful management strategy for these patients.

  12. Acute toxicity and vascular properties of seed of Parkia biglobosa (JACQ) R. Br Gift (Mimosaceae) on rat aorta.

    PubMed

    Ouédraogo, Sylvin; Somé, Noya; Ouattara, Sounkalo; Kini, Félix B; Traore, Aristide; Bucher, Bernard; Guissou, I Pierre

    2012-01-01

    The authors report here the results of study on Parkia biglobosa seeds used in Burkina Faso for arterial hypertension treatment. Investigations were done on acute toxicity and vascular properties of fermented and roasted seeds. Acute toxicity test using mice, revealed by the intraperitoneal route a lethal dose 50 (LD50) of 1800 mg/kg and 1600 mg/kg of body weight for aqueous extract from roasted and fermented seeds respectively. According to the scale of Hodge and Sterner and that of the World Health Organization, such drugs would be classified lightly toxic. Oral administration (up to 3000 mg/kg) did not induce any death of animal. For the vascular properties, the effects of these products were tested on the aorta isolated from rats. The cumulative administration of extract from roasted and fermented seeds (0.1-10 mg/mL) in an organ bath induced a concentration-dependent relaxation of the aorta pre contracted by phenylephrine, with or without functional endothelium. The extracts (10 mg/mL) inhibited for 100% the contraction induced by phenylephrine. The EC50 values in presence and absence of endothelium were respectively of 5.37 ± 0.12 and 4.19 ± 1.02 mg/mL for fermented seeds; for roasted seeds these values were respectively, 5.39 ± 1.12 and 5.93 ± 0.95 mg/mL. Nevertheless, low concentration of roasted seeds (1-4 mg/mL) induced endothelium-dependent relaxation and this effect was inhibited by indomethacin (10⁻⁵M), and not by L-NAME (310⁻⁴M). These experimental results revealed a vasorelaxant effect of P. biglobosa seeds. P. biglobosa seems to act directly on the smooth muscle and via endothelium involving the generation of vasodilatating prostaglandins. This vasodilator effect would be in favor of an anti hypertensive property of P. biglobosa seeds.

  13. Acute effects of whey protein isolate on blood pressure, vascular function and inflammatory markers in overweight postmenopausal women.

    PubMed

    Pal, Sebely; Ellis, Vanessa

    2011-05-01

    Previous evidence indicates that chronic consumption of dairy whey proteins has beneficial effects on CVD risk factors. The present study investigated the postprandial effects of whey protein isolate on blood pressure, vascular function and inflammatory markers in overweight and obese postmenopausal women. This was a randomised, three-way cross-over design study where twenty overweight and obese postmenopausal women consumed a breakfast meal in conjunction with one of three supplements: 45 g whey protein isolate, 45 g sodium caseinate or 45 g of a glucose control. Fasting and postprandial blood samples, blood pressure and pulse wave analysis readings were taken for up to 6 h. After consumption of the meal, both systolic and diastolic blood pressure, and augmentation index (AI) decreased initially for all interventions and gradually returned to baseline levels by 6 h. However, there were no significant differences in AI, systolic or diastolic blood pressure within or between the glucose control, casein or whey groups. There were also no significant group effects on plasma inflammatory markers (IL-6, TNF-α and C-reactive protein). The health effects previously seen with chronic whey protein ingestion were not seen in the acute 6 h postprandial period in relation to blood pressure, vascular function or inflammatory markers when compared with casein and a glucose control. This suggests that such effects are better observed from the long-term consumption of whey proteins.

  14. [[Role of dyslipidemia in pathogenesis of vascular events among Arctic Circle population].

    PubMed

    Maslov, L N; Vychuzhanova, E A; Gorbunov, A S; Tsibul'nikov, S Iu

    2014-01-01

    Habitation within the polar circle increases cardiovascular mortality rate and particularly increases mortality as a result of coronary events. The main reason of elevation of mortality from these diseases is a dyslipidemia which developed more among alien population residing long time in Far North. Dyslipidemia is less found among aboriginal population of Arctic Circle keeping traditional way of life and respectively it is low rate of mortality from coronary heart disease. The data showed that low rate of dyslipidemia among aboriginal population of North regions depends on fish consumption which is high content of Ω3-polyunsaturated fatty acids.

  15. Acute procedural complications and in-hospital events after percutaneous coronary interventions Eptifibatide versus Abciximab

    SciTech Connect

    Ajani, Andrew E.; Waksman, Ron; Gruberg, Luis; Sharma, Arvind K.; Lew, Robert; Pinnow, Ellen; Canos, Daniel A.; Cheneau, Edouard; Castagna, Marco; Satler, Lowell; Pichard, Augusto; Kent, Kenneth M

    2003-03-01

    Background: Glycoprotein IIb/IIIa antagonists reduce peri-angioplasty ischemic complications and improve in-hospital outcome in patients undergoing percutaneous coronary interventions (PCI). Prior studies have demonstrated favorable results with both eptifibatide and abciximab. The purpose of this study was to assess whether there are any differences in rates of acute procedural complications and in-hospital events with the use of these two agents. Methods: A retrospective review of 359 elective PCIs from June 1998 to August 2000 identified 152 PCIs treated with eptifibatide (bolus 180 {mu}g/kg, infusion 2 {mu}g/kg/min for 12-48 h) and 205 PCIs treated with abciximab (bolus 0.25 mg/kg, infusion 10 {mu}g/min for 12 h). All patients received IIb/IIIa antagonists at the initiation of the intervention. Results: The clinical demographics, the angiographic morphology, the indications, and the procedural details were similar in both groups. In the eptifibatide group, the maximum ACT was lower (235{+-}45 vs. 253{+-}40, P<.0001). The incidence of major procedural and in-hospital events was compared. Eptifibatide and abciximab had similar rates of major complications (death or myocardial infarction) (1.4% vs. 2.9%), repeat PTCA (3.4% vs. 1.9%), and major bleeding (3.3% vs. 4.3%). Conclusions: Eptifibatide is comparable to abciximab in regards to acute procedural complications and in-hospital events after PCI.

  16. Dimethylfumarate attenuates restenosis after acute vascular injury by cell-specific and Nrf2-dependent mechanisms

    PubMed Central

    Oh, Chang Joo; Park, Sungmi; Kim, Joon-Young; Kim, Han-Jong; Jeoung, Nam Ho; Choi, Young-Keun; Go, Younghoon; Park, Keun-Gyu; Lee, In-Kyu

    2014-01-01

    Excessive proliferation of vascular smooth muscle cells (VSMCs) and incomplete re-endothelialization is a major clinical problem limiting the long-term efficacy of percutaneous coronary angioplasty. We tested if dimethylfumarate (DMF), an anti-psoriasis drug, could inhibit abnormal vascular remodeling via NF−E2-related factor 2 (Nrf2)-NAD(P)H quinone oxidoreductase 1 (NQO1) activity. DMF significantly attenuated neointimal hyperplasia induced by balloon injury in rat carotid arteries via suppression of the G1 to S phase transition resulting from induction of p21 protein in VSMCs. Initially, DMF increased p21 protein stability through an enhancement in Nrf2 activity without an increase in p21 mRNA. Later on, DMF stimulated p21 mRNA expression through a process dependent on p53 activity. However, heme oxygenase-1 (HO-1) or NQO1 activity, well-known target genes induced by Nrf2, were dispensable for the DMF induction of p21 protein and the effect on the VSMC proliferation. Likewise, DMF protected endothelial cells from TNF-α-induced apoptosis and the dysfunction characterized by decreased eNOS expression. With knock-down of Nrf2 or NQO1, DMF failed to prevent TNF-α-induced cell apoptosis and decreased eNOS expression. Also, CD31 expression, an endothelial specific marker, was restored in vivo by DMF. In conclusion, DMF prevented abnormal proliferation in VSMCs by G1 cell cycle arrest via p21 upregulation driven by Nrf2 and p53 activity, and had a beneficial effect on TNF-α-induced apoptosis and dysfunction in endothelial cells through Nrf2–NQO1 activity suggesting that DMF might be a therapeutic drug for patients with vascular disease. PMID:25009787

  17. Assessing the influence of antivibration glove on digital vascular responses to acute hand-arm vibration.

    PubMed

    Mahbub, Md H; Yokoyama, Kenjiro; Laskar, Md S; Inoue, Masaiwa; Takahashi, Yukio; Yamamoto, Shinji; Harada, Noriaki

    2007-05-01

    This study was designed to assess the influence of an antivibration glove on digital vascular responses in healthy subjects exposed to short-term grasping of a vibrating handle. To measure finger blood flow (FBF) and finger skin temperature (FST) once at the end of every min, a blood flowmeter sensor was attached to the dorsum and a thermistor sensor was attached to the medial surface of the subject's middle phalanx of the third finger of the right hand. After 5 min of baseline measurements without or with an antivibration glove meeting ISO standard 10819, worn on the right hand, subjects gripped a vibrating handle with the same hand for a period of 5 min. Vibration was generated at two frequencies of 31.5 Hz and 250 Hz with a frequency weighted rms acceleration of 5.5 m/s(2). FBF and FST continued to be recorded for a further 5 min after release of the vibrating handle. Statistical analysis showed no significant change after vibration exposure in either FST or FBF at 250 Hz, compared to baseline (control) measurements while using the antivibration glove. At 31.5 Hz, FBF data exhibited a significant difference between before and after grasping of vibrating handle, which was less under the condition of wearing the antivibration glove than under the condition of bare hand. The results provide evidence that the antivibration glove considerably influenced finger vascular changes in healthy subjects induced by vibration exposure, especially against high frequency vibration. Further studies are required to assess finger vascular responses to hand-transmitted vibration with antivibration gloves of different manufacturers.

  18. Clinical outcomes of adverse cardiovascular events in patients with acute dapsone poisoning

    PubMed Central

    Kang, Kyung Sik; Kim, Hyung Il; Kim, Oh Hyun; Cha, Kyoung Chul; Kim, Hyun; Lee, Kang Hyun; Hwang, Sung Oh; Cha, Yong Sung

    2016-01-01

    Objective Adverse cardiovascular events (ACVEs) account for a large proportion of the morbidities and mortalities associated with drug overdose emergencies. However, there are no published reports regarding outcomes of ACVEs associated with acute dapsone poisoning. Here, the authors retrospectively analyzed ACVEs reported within 48 hours of treatment in patients with acute dapsone poisoning and assessed the significance of ACVEs as early predictors of mortality. Methods Sixty-one consecutive cases of acute dapsone poisoning that were diagnosed and treated at a regional emergency center between 2006 and 2014 were included in the study. An ACVE was defined as myocardial injury, shock, ventricular dysrhythmia, cardiac arrest, or any combination of these occurring within the first 48 hours of treatment for acute dapsone poisoning. Results Nineteen patients (31.1%) had evidence of myocardial injury (elevation of serum troponin-I level or electrocardiography signs of ischemia) after dapsone overdose, and there were a total of 19 ACVEs (31.1%), including one case of shock (1.6%). Fourteen patients (23.0%) died from pneumonia or multiple organ failure, and the incidence of ACVEs was significantly higher among non-survivors than among survivors (64.3% vs. 21.3%, P=0.006). ACVE was a significant predictor of mortality (odds ratio, 5.690; 95% confidence interval, 1.428 to 22.675; P=0.014). Conclusion The incidence of ACVE was significantly higher among patients who died after acute dapsone poisoning. ACVE is a significant predictor of mortality after dapsone overdose, and evidence of ACVE should be carefully sought in these patients. PMID:27752614

  19. Dipyridamole technetium-99m sestamibi myocardial tomography in patients evaluated for elective vascular surgery: prognostic value for perioperative and late cardiac events.

    PubMed

    Stratmann, H G; Younis, L T; Wittry, M D; Amato, M; Miller, D D

    1996-05-01

    Dipyridamole thallium-201 myocardial imaging can provide information regarding risk of perioperative cardiac events in patients being considered for vascular surgery. The value for this purpose of myocardial imaging with technetium-99m sestamibi (MIBI), a radiotracer with biokinetic and imaging properties different from thallium-201, has not been established. To this end the prognostic value of dipyridamole MIBI tomography for perioperative and late cardiac events was evaluated in 229 consecutive patients being considered for elective vascular surgery. Vascular surgery was done < or = 3 months after testing in 197 of these patients. Perioperative cardiac events (cardiac death, nonfatal myocardial infarction, unstable angina, or ischemic pulmonary edema) occurred in 9 (5%) patients. The rate of such events was 3% in patients with normal MIBI results, 5% in those with abnormal results, and 6% in patients with a reversible MIBI defect (both p = NS). When patients with abnormal MIBI results who had preoperative cardiac interventions (coronary revascularization or an increase in antiischemic medical therapy) were compared with with those who did not, no significant differences in the occurrence of perioperative cardiac events were found between these two groups either. A group of 172 medically treated patients who survived vascular surgery and did not have a nonfatal perioperative cardiac event was then monitored (mean 21 +/- 14 months) for the occurrence of a serious late cardiac event (nonfatal myocardial infarction or cardiac death). Event-free survival (Mantel-Cox) was significantly less in patients with abnormal studies compared with those with normal scan results. Late cardiac events occurred in 26 (15%) patients, with those having an abnormal MIBI result showing a significantly greater event rate than those with normal results (26% vs 4%, p < 0.0001). The rate of late cardiac events was 33% in patients with a reversible MIBI defect (p < 0.001) and 23% in those

  20. Acute impact of intermittent pneumatic leg compression frequency on limb hemodynamics, vascular function, and skeletal muscle gene expression in humans.

    PubMed

    Sheldon, Ryan D; Roseguini, Bruno T; Thyfault, John P; Crist, Brett D; Laughlin, M H; Newcomer, Sean C

    2012-06-01

    The mechanisms by which intermittent pneumatic leg compression (IPC) treatment effectively treats symptoms associated with peripheral artery disease remain speculative. With the aim of gaining mechanistic insight into IPC treatment, the purpose of this study was to investigate the effect of IPC frequency on limb hemodynamics, vascular function, and skeletal muscle gene expression. In this two study investigation, healthy male subjects underwent an hour of either high-frequency (HF; 2-s inflation/3-s deflation) or low-frequency (LF; 4-s inflation/16-s deflation) IPC treatment of the foot and calf. In study 1 (n = 11; 23.5 ± 4.7 yr), subjects underwent both HF and LF treatment on separate days. Doppler/ultrasonography was used to measure popliteal artery diameter and blood velocity at baseline and during IPC treatment. Flow-mediated dilation (FMD) and peak reactive hyperemia blood flow (RHBF) were determined before and after IPC treatment. In study 2 (n = 19; 22.0 ± 4.6 yr), skeletal muscle biopsies were taken from the lateral gastrocnemius of the treated and control limb at baseline and at 30- and 150-min posttreatment. Quantitative PCR was used to assess mRNA concentrations of genes associated with inflammation and vascular remodeling. No treatment effect on vascular function was observed. Cuff deflation resulted in increased blood flow (BF) and shear rate (SR) in both treatments at the onset of treatment compared with baseline (P < 0.01). BF and SR significantly diminished by 45 min of HF treatment only (P < 0.01). Both treatments reduced BF and SR and elevated oscillatory shear index compared with baseline (P < 0.01) during cuff inflation. IPC decreased the mRNA expression of cysteine-rich protein 61 from baseline and controls (P <0 .01) and connective tissue growth factor from baseline (P < 0.05) in a frequency-dependent manner. In conclusion, a single session of IPC acutely impacts limb hemodynamics and skeletal muscle gene expression in a frequency

  1. Effects of acute and chronic interval sprint exercise performed on a manually propelled treadmill on upper limb vascular mechanics in healthy young men.

    PubMed

    Olver, T Dylan; Reid, Steph M; Smith, Alan R; Zamir, Mair; Lemon, Peter W R; Laughlin, M Harold; Shoemaker, J Kevin

    2016-07-01

    Interval sprint exercise performed on a manually propelled treadmill, where the hands grip the handle bars, engages lower and upper limb skeletal muscle, but little is known regarding the effects of this exercise modality on the upper limb vasculature. We tested the hypotheses that an acute bout of sprint exercise and 6 weeks of training induces brachial artery (BA) and forearm vascular remodeling, favoring a more compliant system. Before and following a single bout of exercise as well as 6 weeks of training three types of vascular properties/methodologies were examined in healthy men: (1) stiffness of the entire upper limb vascular system (pulse wave velocity (PWV); (2) local stiffness of the BA; and (3) properties of the entire forearm vascular bed (determined by a modified lumped parameter Windkessel model). Following sprint exercise, PWV declined (P < 0.01), indices of BA stiffness did not change (P ≥ 0.10), and forearm vascular bed compliance increased and inertance and viscoelasticity decreased (P ≤ 0.03). Following manually propelled treadmill training, PWV remained unchanged (P = 0.31), indices of BA stiffness increased (P ≤ 0.05) and forearm vascular bed viscoelasticity declined (P = 0.02), but resistance, compliance, and inertance remained unchanged (P ≥ 0.10) compared with pretraining values. Sprint exercise induced a more compliant forearm vascular bed, without altering indices of BA stiffness. These effects were transient, as following training the forearm vascular bed was not more compliant and indices of BA stiffness increased. On the basis of these data, we conclude that adaptations to acute and chronic sprint exercise on a manually propelled treadmill are not uniform along the arterial tree in upper limb. PMID:27405970

  2. Effects of acute and chronic interval sprint exercise performed on a manually propelled treadmill on upper limb vascular mechanics in healthy young men.

    PubMed

    Olver, T Dylan; Reid, Steph M; Smith, Alan R; Zamir, Mair; Lemon, Peter W R; Laughlin, M Harold; Shoemaker, J Kevin

    2016-07-01

    Interval sprint exercise performed on a manually propelled treadmill, where the hands grip the handle bars, engages lower and upper limb skeletal muscle, but little is known regarding the effects of this exercise modality on the upper limb vasculature. We tested the hypotheses that an acute bout of sprint exercise and 6 weeks of training induces brachial artery (BA) and forearm vascular remodeling, favoring a more compliant system. Before and following a single bout of exercise as well as 6 weeks of training three types of vascular properties/methodologies were examined in healthy men: (1) stiffness of the entire upper limb vascular system (pulse wave velocity (PWV); (2) local stiffness of the BA; and (3) properties of the entire forearm vascular bed (determined by a modified lumped parameter Windkessel model). Following sprint exercise, PWV declined (P < 0.01), indices of BA stiffness did not change (P ≥ 0.10), and forearm vascular bed compliance increased and inertance and viscoelasticity decreased (P ≤ 0.03). Following manually propelled treadmill training, PWV remained unchanged (P = 0.31), indices of BA stiffness increased (P ≤ 0.05) and forearm vascular bed viscoelasticity declined (P = 0.02), but resistance, compliance, and inertance remained unchanged (P ≥ 0.10) compared with pretraining values. Sprint exercise induced a more compliant forearm vascular bed, without altering indices of BA stiffness. These effects were transient, as following training the forearm vascular bed was not more compliant and indices of BA stiffness increased. On the basis of these data, we conclude that adaptations to acute and chronic sprint exercise on a manually propelled treadmill are not uniform along the arterial tree in upper limb.

  3. Detection of acute synthetic vascular graft infection with IN-111 labeled leukocyte imaging

    SciTech Connect

    Alazraki, N.; Dries, D.; Lawrence, P.; Murphy, K.; Kercher, J.; Datz, F.; Christian, P.; Taylor, A.

    1985-05-01

    Synthetic vascular graft infection is characterized by late diagnosis due to indolent and nonspecific symptoms. Reported data on accuracy of In-111 labeled leukocyte imaging to identify vascular graft infection is sparse and conflicting. The purpose of this animal study was to clarify the accuracy of detection of early graft infection using a mixed population of In-111 labeled leukocytes. Twelve mongrel dogs received dacron aortic interposition grafts. Seven grafts were contaminated at surgery by topical ATCC S. aureus, 10/sup 8/ organisms per ml. Six control animals received no graft contamination Mixed population In-111 homologous leukocyte labeling was performed followed by imaging at 24 and 48 hours following intravenous injection of 250 ..mu..Ci In-111 leukocytes. Scans were done on Day 2 post-surgery. Infected dogs were sacrificed following Indium imaging; control dogs were rescanned at 3 weeks postop and sacrificed thereafter. Autopsy results were correlated with scans, yielding sensitivity 71%, specificity 100%, accuracy 85% for In-111 leukocyte imaging to detect early graft infection. False positive leukocyte imaging in the early postop period was not a problem. At autopsy all 5 dogs with infected grafts and positive scans had gross pus. The 2 dogs with false negative scans showed no gross pus at autopsy; cultures were positive for S. aureus in all 7 dogs. Scans at 2 days and 3 weeks post-surgery were true negatives in all 6 control dogs. These data suggest a high level of clinical reliability of leukocyte imaging for early graft infection detection.

  4. Acute Charcot foot and diabetes: A primer for the vascular nurse.

    PubMed

    Foley, Anne M

    2016-03-01

    The clinical findings of the acute Charcot process includes a swollen, warm, and erythematous foot; although pain may be present, it is often mild and out of proportion to the clinical examination. The diagnosis is confirmed by radiologic imaging, and the diagnosis must be considered in any patient with diabetic neuropathy and unilateral foot swelling. Initial treatment calls for immediate immobilization of the foot. Failure to do so can lead to further foot damage, destruction, and possibly amputation. The patient with acute CN requires referral to a multidisciplinary team experienced in the care of the diabetic patient with this devastating condition. Patient education is a crucial component of the treatment plan when caring for a client with CN. PMID:26897350

  5. Effect of acute and chronic ethanol on the agonist responses of vascular smooth muscle

    SciTech Connect

    Strickland, J.; Wooles, W.R.

    1986-03-05

    The authors studied the effects of ETOH on the response of isolated rat thoracic aorta rings to phenylephrine (PE) and angiotensin II (AII). They also examined the effect of chronic ETOH on vascular reactivity to PE and ETOH in vitro for up to 18 weeks during the development of ETOH-induced hypertension. The dose-responses (DR) of both PE and AII were shifted to the right by ETOH in a dose dependent manner. All was more sensitive to this shift which was significantly different from the controls at 50 mM ETOH compared to 150 mM ETOH for PE. The combination of 1 nM saralasin and 150 mM ETOH depressed the AII DR more than saralasin alone but was comparable to that of ETOH. The combination of 150 mM ETOH and 0.3 nM prazosin depressed the PE DR less than prazosin alone but more than ETOH alone. The effect of .01 nM verapamil on the PE DR was similar to that of saralasin on the AII DR. The results of the chronic study showed that the PE DR of the aortic rings from ETOH rats was comparable to that of control rats until the 18th week when it was shifted to the right. The PE DR was shifted rightward by 150 mM ETOH to the same extent in both control and ETOH rats which suggests that ETOH has ..cap alpha..-receptor blocking properties. Vascular reactivity to PE and to ETOH remained the same throughout the ETOH drinking period indicating a lack of development of hypersensitivity to PE or tolerance to ETOH which may contribute to the hypertensive effect of ETOH.

  6. Walking, cycling, or gardening, with or without seasonal interruption, in relation to acute coronary events.

    PubMed

    Magnus, K; Matroos, A; Strackee, J

    1979-12-01

    The case-referent study reported here investigates the relationship between acute coronary events (ACE) and sustained light physical exercise, mainly leisure-time walking, cycling, or gardening (WCG). These activities are classified as habitual WCG (greater than 8 months/year), seasonal WCG (4--8 months), or occasional WCG (less than 4 months), each category being further subdivided according to the number of hours a week: less than 4 hours, 4--7 hours, or greater than 7 hours. A significant negative association is found between ACE and habitual WCG. No such relationship is evident between ACE and seasonal WCG, however, seasonal WCG being equally frequent (27%) in both cases and referents. These observations may indicate that any effect on the incidence of acute coronary events that is caused by walking, cycling, or gardening is neutralized if these activities are interrupted for several months of the year. The negative association between habitual WCG and ACE does not depend on the number of hours a week devoted to SCG and is not enhanced by more vigorous additional exercise. The fatality of ACE (death rate within 4 weeks) is significantly higher in the least active group (WCG less than 4 months/year).

  7. Effect of acute exercise and cardiovascular fitness on cognitive function: an event-related cortical desynchronization study.

    PubMed

    Chang, Yu-Kai; Chu, Chien-Heng; Wang, Chun-Chih; Song, Tai-Fen; Wei, Gao-Xia

    2015-03-01

    This study aimed to clarify the effects of acute exercise and cardiovascular fitness on cognitive function using the Stroop test and event-related desynchronization (ERD) in an aged population. Old adults (63.10 ± 2.89 years) were first assigned to either a high-fitness or a low-fitness group, and they were then subjected to an acute exercise treatment and a reading control treatment in a counterbalanced order. Alpha ERD was recorded during the Stroop test, which was administered after both treatments. Acute exercise improved cognitive performance regardless of the level of cognition, and old adults with higher fitness levels received greater benefits from acute exercise. Additionally, acute exercise, rather than overall fitness, elicited greater lower and upper alpha ERDs relative to the control condition. These findings indirectly suggest that the beneficial effects of acute exercise on cognitive performance may result from exercise-induced attentional control observed during frontal neural excitation. PMID:25308605

  8. No Additional Prognostic Value of Genetic Information in the Prediction of Vascular Events after Cerebral Ischemia of Arterial Origin: The PROMISe Study

    PubMed Central

    Achterberg, Sefanja; Kappelle, L. Jaap; de Bakker, Paul I. W.; Traylor, Matthew; Algra, Ale

    2015-01-01

    Background Patients who have suffered from cerebral ischemia have a high risk of recurrent vascular events. Predictive models based on classical risk factors typically have limited prognostic value. Given that cerebral ischemia has a heritable component, genetic information might improve performance of these risk models. Our aim was to develop and compare two models: one containing traditional vascular risk factors, the other also including genetic information. Methods and Results We studied 1020 patients with cerebral ischemia and genotyped them with the Illumina Immunochip. Median follow-up time was 6.5 years; the annual incidence of new ischemic events (primary outcome, n=198) was 3.0%. The prognostic model based on classical vascular risk factors had an area under the receiver operating characteristics curve (AUC-ROC) of 0.65 (95% confidence interval 0.61-0.69). When we added a genetic risk score based on prioritized SNPs from a genome-wide association study of ischemic stroke (using summary statistics from the METASTROKE study which included 12389 cases and 62004 controls), the AUC-ROC remained the same. Similar results were found for the secondary outcome ischemic stroke. Conclusions We found no additional value of genetic information in a prognostic model for the risk of ischemic events in patients with cerebral ischemia of arterial origin. This is consistent with a complex, polygenic architecture, where many genes of weak effect likely act in concert to influence the heritable risk of an individual to develop (recurrent) vascular events. At present, genetic information cannot help clinicians to distinguish patients at high risk for recurrent vascular events. PMID:25906364

  9. 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

  10. Acute effects of different types of oil consumption on endothelial function, oxidative stress status and vascular inflammation in healthy volunteers.

    PubMed

    Tousoulis, Dimitris; Papageorgiou, Nikolaos; Antoniades, Charalambos; Giolis, Anastasios; Bouras, George; Gounari, Panagiota; Stefanadi, Elli; Miliou, Antigoni; Psaltopoulou, Theodora; Stefanadis, Christodoulos

    2010-01-01

    Consumption of different types of oil may have different effects on cardiovascular risk. The exact role of maize oil, cod liver oil, soya oil and extra virgin olive oil on endothelial function, oxidative stress and inflammation is unknown. We evaluated the effect of acute consumption of these types of oil on endothelial function, oxidative stress and inflammation in healthy adults. Thirty-seven healthy volunteers were randomised to receive an oral amount of each type of oil or water. Endothelial function was evaluated by gauge-strain plethysmography at baseline and 1, 2 and 3 h after consumption. Oxidative stress status was determined by total lipid peroxides (PEROX), while inflammatory process was estimated by measuring the soluble form of vascular adhesion molecule 1. Serum levels of the two previous markers were measured at baseline and 3 h after oil consumption. Reactive hyperaemia (RH) was significantly decreased after maize oil consumption compared with controls (P < 0.05). However, the consumption of cod liver oil and soya oil induced a significant improvement of RH after 1 h, compared with controls (P < 0.05). There was no significant effect of any type of oil consumption on endothelium-independent dilatation, total lipid PEROX and vascular adhesion molecule 1 serum levels. Consumption of maize oil leads to impaired endothelial function, while soya oil and cod liver oil slightly improve endothelial function. However, all types of oils did not affect inflammatory process and systemic oxidative stress, suggesting that their effect on endothelial function may not be mediated by free radicals bioavailability.

  11. Smooth muscle calcium and endothelium-derived relaxing factor in the abnormal vascular responses of acute renal failure.

    PubMed Central

    Conger, J D; Robinette, J B; Schrier, R W

    1988-01-01

    Abnormal renovascular reactivity, characterized by paradoxical vasoconstriction to a reduction in renal perfusion pressure (RPP) in the autoregulatory range, increased sensitivity to renal nerve stimulation (RNS), and loss of vasodilatation to acetylcholine have all been demonstrated in ischemic acute renal failure (ARF). To determine if ischemic injury alters vascular contractility by increasing smooth muscle cell calcium or calcium influx, the renal blood flow (RBF) response to reductions in RPP within the autoregulatory range and to RNS were tested before and after a 90-min intrarenal infusion of verapamil or diltiazem in 7-d ischemic ARF rats. Both calcium entry blockers, verapamil and diltiazem, blocked the aberrant vasoconstrictor response to a reduction in RPP and RNS (both P less than 0.001). In a second series of experiments the potential role of an ischemia-induced endothelial injury and of the absence of endothelium-derived relaxing factor (EDRF) production were examined to explain the lack of vasodilatation to acetylcholine. Acetylcholine, bradykinin (a second EDRF-dependent vasodilator), or prostacyclin, an EDRF-independent vasodilator, was infused intrarenally for 90 min, and RBF responses to a reduction in RPP and RNS were tested in 7-d ischemic ARF rats. Neither acetylcholine nor bradykinin caused vasodilatation or altered the slope of the relationship between RBF and RPP. By contrast, prostacyclin increased RBF (P less than 0.001), but did not change the vascular response to changes in RPP. It was concluded that the abnormal pressor sensitivity to a reduction in RPP and RNS was due to changes in renovascular smooth muscle cell calcium activity that could be blocked by calcium entry blockers. A lack of response to EDRF-dependent vasodilators, as a result of ischemic endothelial injury, may contribute to the increased pressor sensitivity of the renal vessels. PMID:3261301

  12. MEK1/2 inhibitors reverse acute vascular occlusion in mouse models of sickle cell disease.

    PubMed

    Zhao, Yulin; Schwartz, Evan A; Palmer, Gregory M; Zennadi, Rahima

    2016-03-01

    In sickle cell disease (SCD), treatment of recurrent vasoocclusive episodes, leading to pain crises and organ damage, is still a therapeutic challenge. Vasoocclusion is caused primarily by adherence of homozygous for hemoglobin S (SS) red blood cells (SSRBCs) and leukocytes to the endothelium. We tested the therapeutic benefits of MEK1/2 inhibitors in reversing vasoocclusion in nude and humanized SCD mouse models of acute vasoocclusive episodes using intravital microscopy. Administration of 0.2, 0.3, 1, or 2 mg/kg MEK1/2 inhibitor to TNF-α-pretreated nude mice before human SSRBC infusion inhibited SSRBC adhesion in inflamed vessels, prevented the progression of vasoocclusion, and reduced SSRBC organ sequestration. By use of a more clinically relevant protocol, 0.3 or 1 mg/kg MEK1/2 inhibitor given to TNF-α-pretreated nude mice after human SSRBC infusion and onset of vasoocclusion reversed SSRBC adhesion and vasoocclusion and restored blood flow. In SCD mice, 0.025, 0.05, or 0.1 mg/kg MEK1/2 inhibitor also reversed leukocyte and erythrocyte adhesion after the inflammatory trigger of vasoocclusion and improved microcirculatory blood flow. Cell adhesion was reversed by shedding of endothelial E-selectin, P-selectin, and αvβ3 integrin, and leukocyte CD44 and β2 integrin. Thus, MEK1/2 inhibitors, by targeting the adhesive function of SSRBCs and leukocytes, could represent a valuable therapeutic intervention for acute sickle cell vasoocclusive crises.

  13. Contribution of G-CSF to the acute mobilization of endothelial precursor cells by vascular disrupting agents

    PubMed Central

    Shaked, Yuval; Tang, Terence; Woloszynek, Jill; Daenen, Laura G.; Man, Shan; Xu, Ping; Cai, Shi-Rong; Arbeit, Jeffrey M.; Voest, Emile E.; Chaplin, David; Smythe, Jon; Harris, Adrian; Nathan, Paul; Judson, Ian; Rustin, Gordon; Bertolini, Francesco; Link, Daniel C.; Kerbel, Robert S.

    2009-01-01

    Vascular disrupting agents (VDAs) cause acute shutdown of abnormal established tumor vasculature, followed by massive intratumoral hypoxia and necrosis. However, a viable rim of tumor tissue invariably remains from which tumor regrowth rapidly resumes. We have recently shown that an acute systemic mobilization and homing of bone marrow derived circulating endothelial precursor cells (CEPs) can promote tumor regrowth following treatment with either a VDA or certain chemotherapy drugs. The molecular mediators of this systemic reactive host process are unknown. Here we show that following treatment of mice with OXi-4503, a second generation potent pro-drug derivative of combretastatin-A 4 phosphate (CA4P), rapid increases in circulating plasma VEGF, SDF-1, and G-CSF levels are detected. With the aim of determining whether G-CSF is involved in VDA-induced CEP mobilization, mutant G-CSF-R−/− mice were treated with OXI-4503. We found that as opposed to wildtype controls, G-CSF-R−/− mice failed to mobilize CEPs or show induction of SDF-1 plasma levels. Furthermore, Lewis lung carcinomas grown in such mice treated with OXi-4503 showed greater levels of necrosis compared to tumors treated in wildtype mice. Evidence for rapid elevations in circulating plasma G-CSF, VEGF, and SDF-1 were also observed in VDA (CA4P) treated cancer patients. These results highlight the possible impact of drug-induced G-CSF on tumor re-growth following certain cytotoxic drug therapies, in this case using a VDA, and hence G-CSF as a possible therapeutic target. PMID:19738066

  14. Dipyridamole-thallium-201 scintigraphy in the prediction of future cardiac events after acute myocardial infarction

    SciTech Connect

    Leppo, J.A.; O'Brien, J.; Rothendler, J.A.; Getchell, J.D.; Lee, V.W.

    1984-04-19

    To evaluate the safety and usefulness of serial thallium scanning immediately after intravenous dipyridamole, we studied 51 patients recovering from acute myocardial infarction. Eight patients experienced angina during the procedure, but there were no serious complications. Patients were followed for a mean period of 19 months after hospital discharge. Eleven of 12 patients who died during follow-up or had another infarction had shown transient defects (redistribution) on their predischarge scan, as had 22 of the 24 patients who needed readmission for management of angina. Among all the other clinical or scintigraphic criteria tested, the presence of redistribution on the dipyridamole-thallium scan was the only significant predictor of these serious cardiac events. Twenty-six patients were also given a submaximal exercise test before discharge, of whom 13 subsequently had serious cardiac events. The exercise test had been positive in only 6 of these 13 patients, whereas the dipyridamole-thallium scan had shown a redistribution pattern in 12 (P less than 0.001). We conclude from this preliminary study that dipyridamole-thallium scintigraphy after myocardial infraction is relatively safe. It appears to be a more sensitive predictor of subsequent cardiac events than a submaximal exercise test and may therefore prove useful in evaluating patients after recovery from a myocardial infarction.

  15. The Synthetic Tie2 Agonist Peptide Vasculotide Protects Renal Vascular Barrier Function In Experimental Acute Kidney Injury

    PubMed Central

    Rübig, Eva; Stypmann, Jörg; Van Slyke, Paul; Dumont, Daniel J; Spieker, Tilmann; Buscher, Konrad; Reuter, Stefan; Goerge, Tobias; Pavenstädt, Hermann; Kümpers, Philipp

    2016-01-01

    Microvascular barrier dysfunction plays a major role in the pathophysiology of acute kidney injury (AKI). Angiopoietin-1, the natural agonist ligand for the endothelial-specific Tie2 receptor, is a non-redundant endothelial survival and vascular stabilization factor. Here we evaluate the efficacy of a polyethylene glycol-clustered Tie2 agonist peptide, vasculotide (VT), to protect against endothelial-cell activation with subsequent microvascular dysfunction in a murine model of ischemic AKI. Renal ischemia reperfusion injury (IRI) was induced by clamping of the renal arteries for 35 minutes. Mice were treated with VT or PEGylated cysteine before IRI. Sham-operated animals served as time-matched controls. Treatment with VT significantly reduced transcapillary albumin flux and renal tissue edema after IRI. The protective effects of VT were associated with activation of Tie2 and stabilization of its downstream effector, VE-cadherin in renal vasculature. VT abolished the decline in renal tissue blood flow, attenuated the increase of serum creatinine and blood urea nitrogen after IRI, improved recovery of renal function and markedly reduced mortality compared to PEG [HR 0.14 (95% CI 0.05–0.78) P < 0.05]. VT is inexpensive to produce, chemically stable and unrelated to any Tie2 ligands. Thus, VT may represent a novel therapy to prevent AKI in patients. PMID:26911791

  16. Load dependence of changes in forearm and peripheral vascular resistance after acute leg exercise in man.

    PubMed Central

    Piepoli, M; Isea, J E; Pannarale, G; Adamopoulos, S; Sleight, P; Coats, A J

    1994-01-01

    1. It is known that acute exercise is often followed by a reduction in arterial blood pressure. Little is known about the time course of the recovery of the blood pressure or the influence of the intensity of the exercise on this response. Controversy exists, in particular, concerning the changes in peripheral resistance that occur during this period. 2. Eight normal volunteers performed, in random order on separate days, voluntary upright bicycle exercise of three different intensities (maximal, moderate and minimal load) and, on another day, a control period of sitting on a bicycle. They were monitored for 60 min after each test. 3. Diastolic pressure fell after maximal exercise at 5 min (-15.45 mmHg) and 60 min (-9.45 mmHg), compared with the control day. Systolic and mean pressure also fell (non-significantly) after 45 min; heart rate was significantly elevated for the whole hour of recovery (at 60 min, +7.23 beats min-1). No changes in post-exercise blood pressure and heart rate were observed on the days of moderate and minimal exercises. 4. An increase in cardiac index was observed after maximal exercise compared with control (at 60 min, 2.6 +/- 0.3 vs. 1.9 +/- 0.2 l min-1 m-2). This was entirely accounted for by the persistent increase in heart rate, with no significant alteration in stroke volume after exercise on any day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7965851

  17. Quality of Life of Patients After an Acute Coronary Event: Hospital Discharge

    PubMed Central

    Dias, Cristiane Maria Carvalho Costa; Macedo, Luciana Bilitario; Gomes, Lilian Tapioca Jones Cunha; de Oliveira, Paula Luzia Seixas Pereira; Albuquerque, Iana Verena Santana; Lemos, Amanda Queiroz; Brasil, Cristina Aires; Prado, Eloisa Pires Ferreira; Macedo, Pedro Santiago; de Oliveira, Francisco Tiago Oliveira; dos Reis, Helena Franca Correia; Darze, Eduardo Sahade; Guimaraes, Armenio Costa

    2014-01-01

    Background The acute coronary syndrome (ACS) has a high morbi-mortality rate, including physical deficiencies and functional limitations with impact on quality of life. Cardiovascular rehabilitation 1 (CVR1) should begin as early as possible, to enable improvement in functional capacity and quality of life. Previous studies have shown association of cardiovascular diseases with quality of life, in which depression and anxiety are the domains most altered. The aim of the study is to verify the impact of an acute coronary event on quality of life at the moment of hospital discharge. Methodology This was a cross-sectional study, with ACS patients hospitalized in ICU of a private hospital in the city of Salvador, Brazil, submitted to CVR1. The quality of life questionnaire Euroqol-5D was applied on discharge from hospital. Patients included in the study were those with ACV, who had medical permission to walk, had not been submitted to acute surgical treatment, were time and space oriented, and over the age of 18 years. Patients excluded from the study were those with cognitive, orthopedic and neurological problems, who used orthesis on a lower limb, and were in any condition of risk at the time of beginning with CVR1. Data were collected by a previously trained ICU team. Results Data were collected of 63 patients who revealed compromise in the domains of pain/feeling ill (20.63%) and anxiety/depression (38.09%). Statistical significance was observed in the association between sex and pain/feeling ill (P < 0.01), sex and anxiety/depression (P < 0.01), diabetes and mobility (P < 0.01), hereditary factors and anxiety/depression (p < 0.01), BMI and pain/feeling ill (P < 0.01). Conclusion In this sample of patients, on discharge from hospital after ACS, the pain/feeling ill and anxiety/depression domains were shown to be compromised. PMID:25110540

  18. Treatment and outcomes of patients with suspected acute coronary syndromes in relation to initial diagnostic impressions (insights from the Canadian Global Registry of Acute Coronary Events [GRACE] and Canadian Registry of Acute Coronary Events [CANRACE]).

    PubMed

    Bajaj, Ravi R; Goodman, Shaun G; Yan, Raymond T; Bagnall, Alan J; Gyenes, Gabor; Welsh, Robert C; Eagle, Kim A; Brieger, David; Ramanathan, Krishnan; Grondin, Francois R; Yan, Andrew T

    2013-01-15

    The early diagnosis of acute coronary syndrome (ACS) remains challenging, and a considerable proportion of patients are diagnosed with "possible" ACS on admission. The Global Registry of Acute Coronary Events (GRACE/GRACE(2)) and Canadian Registry of Acute Coronary Events (CANRACE) enrolled 16,618 Canadian patients with suspected ACS in 1999 to 2008. We compared the demographic and clinical characteristics, use of cardiac procedures, prognostic accuracy of the GRACE risk score, and in-hospital outcomes between patients given an admission diagnosis of "definite" versus "possible" ACS by the treating physician. Overall, 11,152 and 5,466 patients were given an initial diagnosis of "definite" ACS and "possible" ACS, respectively. Patients with a "possible" ACS had higher GRACE risk score (median 130 vs 125) and less frequently received aspirin, clopidogrel, heparin, or β blockers within the first 24 hours of presentation and assessment of left ventricular function, stress testing, cardiac catheterization, and percutaneous coronary intervention (all p <0.05). Patients with "possible" ACS had greater rates of in-hospital myocardial infarction (9.0% vs 2.0%, p <0.05) and heart failure (12% vs 8.9%, p <0.05). The GRACE risk score demonstrated excellent discrimination for in-hospital mortality in both groups and for the entire study population. In conclusion, compared to patients with "definite" ACS on presentation, those with "possible" ACS had higher baseline GRACE risk scores but less frequently received evidence-based medical therapies within 24 hours of admission or underwent cardiac procedures during hospitalization. The GRACE risk score provided accurate risk assessment, regardless of the initial diagnostic impression.

  19. Imaging Plaques to Predict and Better Manage Patients with Acute Coronary Events

    PubMed Central

    Garcia-Garcia, Hector M.; Jang, Ik-Kyung; Serruys, Patrick W.; Kovacic, Jason C.; Narula, Jagat; Fayad, Zahi A.

    2014-01-01

    Culprit lesions of patients who have had an acute coronary syndrome commonly are ruptured coronary plaques with superimposed thrombus. The precursor of such lesions is an inflamed thin-capped fibroatheroma. These plaques can be imaged by means of invasive techniques such as intravascular ultrasound (and derived techniques), optical coherence tomography and near-infrared spectroscopy. Very often these patients exhibit similar (multiple) plaques beyond the culprit lesion. These remote plaques can be assessed non invasively by computed tomography angiography and magnetic resonance imaging and also using invasive imaging. The detection of these remote plaques is not only feasible, but also in natural history studies have been associated with clinical coronary events. Different systemic pharmacological treatments have been studied (mostly statins) with modest success and therefore newer approaches are being tested. Local treatment for such lesions is in its infancy and larger, prospective and randomized trials are needed. This review will describe the pathological and imaging findings in culprit lesions of patients with acute coronary syndrome and as well as the assessment of remote plaques. In addition, the pharmacological and local treatment options will be reviewed. PMID:24902974

  20. Imaging plaques to predict and better manage patients with acute coronary events.

    PubMed

    Garcia-Garcia, Hector M; Jang, Ik-Kyung; Serruys, Patrick W; Kovacic, Jason C; Narula, Jagat; Fayad, Zahi A

    2014-06-01

    Culprit lesions of patients, who have had an acute coronary syndrome commonly, are ruptured coronary plaques with superimposed thrombus. The precursor of such lesions is an inflamed thin-capped fibroatheroma. These plaques can be imaged by means of invasive techniques, such as intravascular ultrasound (and derived techniques), optical coherence tomography, and near-infrared spectroscopy. Often these patients exhibit similar (multiple) plaques beyond the culprit lesion. These remote plaques can be assessed noninvasively by computed tomographic angiography and MRI and also using invasive imaging. The detection of these remote plaques is not only feasible but also in natural history studies have been associated with clinical coronary events. Different systemic pharmacological treatments have been studied (mostly statins) with modest success and, therefore, newer approaches are being tested. Local treatment for such lesions is in its infancy and larger, prospective, and randomized trials are needed. This review will describe the pathological and imaging findings in culprit lesions of patients with acute coronary syndrome and the assessment of remote plaques. In addition, the pharmacological and local treatment options will be reviewed.

  1. 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.

  2. Low rate of cardiovascular events in patients with acute myocarditis diagnosed by cardiovascular magnetic resonance

    PubMed Central

    De Stefano, Luciano; Yeyati, Ezequiel Levy; Pietrani, Marcelo; Kohan, Andres; Falconi, Mariano; Benger, Juan; Dragonetti, Laura; Garcia-Monaco, Ricardo; Cagide, Arturo

    2014-01-01

    Background Myocarditis is a relatively common inflammatory disease that affects the myocardium. Infectious disease accounts for most of the cases either because of a direct viral infection or post-viral immune-mediated reaction. Cardiovascular magnetic resonance (CMR) has become an established non-invasive diagnosis tool for acute myocarditis. A recent large single centre study with patients with biopsy-proven viral myocarditis undergoing CMR scans found a high rate of mortality. The aim of this study was to assess the rate of clinical events in our population of patients with diagnosed myocarditis by CMR scan. Methods Patients who consulted to the emergency department with diagnosis of myocarditis by CMR were retrospectively included in the study from January 2008 to May 2012. A CMR protocol was used in all patients, and were followed up to assess the rate of the composite endpoint of all-cause death, congestive heart failure, sudden cardiac death, hospitalization for cardiac cause, recurrent myocarditis or need of radiofrequency ablation or implantable cardiac defibrillator (ICD). A descriptive statistical analysis was performed. Results Thirty-two patients with myocarditis were included in the study. The mean age was 42.6±21.2 years and 81.2% were male. In a mean follow up of 30.4±17.8 months, the rate of the composite endpoint of all-cause death, congestive heart failure, sudden cardiac death, hospitalization for cardiac cause, recurrent myocarditis or need of radiofrequency ablation or ICD was 15.6% (n=5). Two patients had heart failure (one of them underwent heart transplant), one patient needed ICD because of ventricular tachycardia and two other patients were re-hospitalized, for recurrent chest pain and for recurrent myocarditis respectively. Conclusions In our series of acute myocarditis diagnosed by CMR we found a low rate of cardiovascular events without mortality. These findings might oppose data from recently published myocarditis trials. PMID

  3. Crosstalk between ACE2 and PLGF regulates vascular permeability during acute lung injury

    PubMed Central

    Wang, Lantao; Li, Yong; Qin, Hao; Xing, Dong; Su, Jie; Hu, Zhenjie

    2016-01-01

    Angiotensin converting enzyme 2 (ACE2) treatment suppresses the severity of acute lung injury (ALI), through antagonizing hydrolyzing angiotensin II (AngII) and the ALI-induced apoptosis of pulmonary endothelial cells. Nevertheless, the effects of ACE2 on vessel permeability and its relationship with placental growth factor (PLGF) remain ill-defined. In the current study, we examined the relationship between ACE2 and PLGF in ALI model in mice. We used a previously published bleomycin method to induce ALI in mice, and treated the mice with ACE2. We analyzed the levels of PLGF in these mice. The mouse lung vessel permeability was determined by a fluorescence pharmacokinetic assay following i.v. injection of 62.5 µg/kg Visudyne. PLGF pump or soluble Flt-1 (sFlt-1) pump was given to augment or suppress PLGF effects, respectively. The long-term effects on lung function were determined by measurement of lung resistance using methacholine. We found that ACE2 treatment did not alter PLGF levels in lung, but antagonized the effects of PLGF on increases of lung vessel permeability. Ectogenic PLGF abolished the antagonizing effects of ACE2 on the vessel permeability against PLGF. On the other hand, suppression of PLGF signaling mimicked the effects of ACE2 on the vessel permeability against PLGF. The suppression of vessel permeability resulted in improvement of lung function after ALI. Thus, ACE2 may antagonize the PLGF-mediated increases in lung vessel permeability during ALI, resulting in improvement of lung function after ALI. PMID:27158411

  4. Vitamin D deficiency contributes to vascular damage in sustained ischemic acute kidney injury.

    PubMed

    de Bragança, Ana C; Volpini, Rildo A; Mehrotra, Purvi; Andrade, Lúcia; Basile, David P

    2016-07-01

    Reductions in renal microvasculature density and increased lymphocyte activity may play critical roles in the progression of chronic kidney disease (CKD) following acute kidney injury (AKI) induced by ischemia/reperfusion injury (IRI). Vitamin D deficiency is associated with tubulointerstitial damage and fibrosis progression following IRI-AKI We evaluated the effect of vitamin D deficiency in sustained IRI-AKI, hypothesizing that such deficiency contributes to the early reduction in renal capillary density or alters the lymphocyte response to IRI Wistar rats were fed vitamin D-free or standard diets for 35 days. On day 28, rats were randomized into four groups: control, vitamin D deficient (VDD), bilateral IRI, and VDD+IRI Indices of renal injury and recovery were evaluated for up to 7 days following the surgical procedures. VDD rats showed reduced capillary density (by cablin staining), even in the absence of renal I/R. In comparison with VDD and IRI rats, VDD+IRI rats manifested a significant exacerbation of capillary rarefaction as well as higher urinary volume, kidney weight/body weight ratio, tissue injury scores, fibroblast-specific protein-1, and alpha-smooth muscle actin. VDD+IRI rats also had higher numbers of infiltrating activated CD4(+) and CD8(+) cells staining for interferon gamma and interleukin-17, with a significant elevation in the Th17/T-regulatory cell ratio. These data suggest that vitamin D deficiency impairs renal repair responses to I/R injury, exacerbates changes in renal capillary density, as well as promoting fibrosis and inflammation, which may contribute to the transition from AKI to CKD.

  5. 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.

  6. 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. PMID:19276707

  7. An Enduring Somatic Threat Model of Posttraumatic Stress Disorder Due to Acute Life-Threatening Medical Events

    PubMed Central

    Edmondson, Donald

    2014-01-01

    Posttraumatic stress disorder (PTSD) occurs in 12-25% of survivors of acute life-threatening medical events such as heart attack, stroke, and cancer, and is associated with recurrence of cardiac events and mortality in heart attack survivors. This article reviews the current state of knowledge about PTSD after such events, and proposes an Enduring Somatic Threat (EST) model of PTSD due to acute life-threatening medical events to address underappreciated differences between PTSD due to past, discrete/external traumatic events (such as combat) and PTSD due to acute manifestations of chronic disease that are enduring/internal in nature (such as heart attack and stroke). The differences include the external versus internal/somatic source of the threat, the past versus present/future temporal focus of threatening cognitions, the different types and consequences of avoidance behavior, and the different character and consequences of hyperarousal. Although important differences between the two types of PTSD exist, the EST model proposes that the underlying fear of mortality maintains PTSD symptoms due to both discrete/external and ongoing/somatic events. Finally, this article offers a research agenda for testing the EST model, with a particular focus on areas that may improve cardiovascular prognosis and health behaviors in survivors of heart attack and stroke. PMID:24920956

  8. Glutathione (GSH) and the GSH synthesis gene Gclm modulate plasma redox and vascular responses to acute diesel exhaust inhalation in mice

    PubMed Central

    Weldy, Chad S.; Luttrell, Ian P.; White, Collin C.; Morgan-Stevenson, Vicki; Cox, David P.; Carosino, Christopher M.; Larson, Timothy V.; Stewart, James A.; Kaufman, Joel D.; Kim, Francis; Chitaley, Kanchan; Kavanagh, Terrance J.

    2013-01-01

    Context Inhalation of fine particulate matter (PM2.5) is associated with acute pulmonary inflammation and impairments in cardiovascular function. In many regions, PM2.5 is largely derived from diesel exhaust (DE), and these pathophysiological effects may be due in part to oxidative stress resulting from DE inhalation. The antioxidant glutathione (GSH) is important in limiting oxidative stress-induced vascular dysfunction. The rate-limiting enzyme in GSH synthesis is glutamate cysteine ligase and polymorphisms in its catalytic and modifier subunits (GCLC and GCLM) have been shown to influence vascular function and risk of myocardial infarction in humans. Objective We hypothesized that compromised de novo synthesis of GSH in Gclm−/+ mice would result in increased sensitivity to DE-induced lung inflammation and vascular effects. Materials and methods WT and Gclm−/+ mice were exposed to DE via inhalation (300 µg/m3) for 6 h. Neutrophil influx into the lungs, plasma GSH redox potential, vascular reactivity of aortic rings and aortic nitric oxide (NO•) were measured. Results DE inhalation resulted in mild bronchoalveolar neutrophil influx in both genotypes. DE-induced effects on plasma GSH oxidation and acetylcholine (ACh)-relaxation of aortic rings were only observed in Gclm−/+ mice. Contrary to our hypothesis, DE exposure enhanced ACh-induced relaxation of aortic rings in Gclm−/+ mice. Discussion and conclusion These data support the hypothesis that genetic determinants of antioxidant capacity influence the biological effects of acute inhalation of DE. However, the acute effects of DE on the vasculature may be dependent on the location and types of vessels involved. Polymorphisms in GSH synthesis genes are common in humans and further investigations into these potential gene-environment interactions are warranted. PMID:23808636

  9. Expression of vascular endothelial growth factor and basic fibroblast growth factor in acute rejection reaction following rat orthotopic liver transplantation.

    PubMed

    Zhang, Changsong; Yang, Guangshun; Lu, Dewen; Ling, Yang; Chen, Guihua; Zhou, Tianbao

    2014-08-01

    The aim of the present study was to investigate the expression levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in acute rejection reaction (ARR) following orthotopic liver transplantation in a rat model. Serum VEGF and bFGF levels were detected using ELISA, and their expression levels in liver and spleen tissues were determined using immunohistochemistry. The mRNA expression levels of VEGF and bFGF were detected by conducting a quantitative polymerase chain reaction during the ARR following orthotopic liver transplantation. The expression levels of VEGF and bFGF in the serum 3 days following liver transplantation were significantly higher compared with those in the other groups (1 and 7 days following transplantation; P<0.01). In addition, the numbers of cells in the liver tissue that were shown to be positive for the expression VEGF and bFGF using immunohistochemistry were significantly higher 3 days following transplantation than at the other time points (P<0.0001). Furthermore, the numbers of cells positive for VEGF and bFGF expression in the spleen detected 3 days following the transplantation surgery were also significantly higher compared with those at the other time points (P<0.01). VEGF and bFGF mRNA expression levels were also increased from 1 day following the surgery and reached a peak at day 3, prior to declining gradually and remaining at a relatively high level. VEGF and bFGF mRNA expression levels changed dynamically, by peaking and then declining, in ARR following orthotopic liver transplantation. These changes may have an important impact on angiogenesis and the inflammatory reaction, and the identification of these changes increases the current understanding of ARR following orthotopic liver transplantation.

  10. Design and Rationale of Gulf locals with Acute Coronary Syndrome Events (Gulf Coast) Registry

    PubMed Central

    Zubaid, Mohammad; Thani, Khalid Bin; Rashed, Wafa; Alsheikh-Ali, Alawi; Alrawahi, Najib; Ridha, Mustafa; Akbar, Mousa; Alenezi, Fahad; Alhamdan, Rashed; Almahmeed, Wael; Ouda, Hussam; Al-Mulla, Arif; Baslaib, Fahad; Shehab, Abdulla; Alnuaimi, Abdulla; Amin, Haitham; Krumholz, Harlan M

    2014-01-01

    Objectives: To describe the risk profile, management and one-year outcomes of patients hospitalized with acute coronary syndrome (ACS) in the Gulf region of the Middle East. Subjects and Methods: The Gulf locals with acute coronary syndrome events (Gulf COAST) registry is a prospective, multinational, longitudinal, observational, cohort-based registry of consecutive citizens, from the Gulf region of the Middle East, admitted from January 2012 to January 2013 to 29 hospitals with a diagnosis of ACS. Data entered online included patient demographics, cardiovascular risk profiles, past medical history, physical findings on admission, in-hospital diagnostic tests and therapeutic management, as well as one year outcomes. Results: 3188 patients were recruited. The mean age was 60.4 ± 12.6years (range: 22-112), 2104 (66%) were males and 1084 (34%) females. The discharge diagnosis was ST-segment elevation myocardial infarction (STEMI) in 741 (23.2%), new-onset left bundle branch block myocardial infarction (LBBBMI) in 30 (0.9%), non-ST-segment elevation myocardial infarction (NSTEMI) in 1486 (46.6%) and unstable angina in 931 (29.2%). At hospital presentation, 2105 (66%), 1779 (55.8%), 1703 (53.4%) and 740 (23.2%) had history of hypertension, dyslipidemia, diabetes mellitus and active smoking, respectively. Conclusion: Patients with ACS in our region are young with very high risk profile. The Gulf COAST registry is an example of successful regional collaboration and will provide information on contemporary management of ACS in the region. PMID:25328551

  11. Acute hematological effects of solar particle event proton radiation in the porcine model.

    PubMed

    Sanzari, J K; Wan, X S; Wroe, A J; Rightnar, S; Cengel, K A; Diffenderfer, E S; Krigsfeld, G S; Gridley, D S; Kennedy, A R

    2013-07-01

    Acute radiation sickness (ARS) is expected to occur in astronauts during large solar particle events (SPEs). One parameter associated with ARS is the hematopoietic syndrome, which can result from decreased numbers of circulating blood cells in those exposed to radiation. The peripheral blood cells are critical for an adequate immune response, and low blood cell counts can result in an increased susceptibility to infection. In this study, Yucatan minipigs were exposed to proton radiation within a range of skin dose levels expected for an SPE (estimated from previous SPEs). The proton-radiation exposure resulted in significant decreases in total white blood cell count (WBC) within 1 day of exposure, 60% below baseline control value or preirradiation values. At the lowest level of the blood cell counts, lymphocytes, neutrophils, monocytes and eosinophils were decreased up to 89.5%, 60.4%, 73.2% and 75.5%, respectively, from the preirradiation values. Monocytes and lymphocytes were decreased by an average of 70% (compared to preirradiation values) as early as 4 h after radiation exposure. Skin doses greater than 5 Gy resulted in decreased blood cell counts up to 90 days after exposure. The results reported here are similar to studies of ARS using the nonhuman primate model, supporting the use of the Yucatan minipig as an alternative. In addition, the high prevalence of hematologic abnormalities resulting from exposure to acute, whole-body SPE-like proton radiation warrants the development of appropriate countermeasures to prevent or treat ARS occurring in astronauts during space travel.

  12. Urgent carotid endarterectomy in patients with acute neurological ischemic events within six hours after symptoms onset.

    PubMed

    Gajin, P; Radak, Dj; Tanaskovic, S; Babic, S; Nenezic, D

    2014-06-01

    To analyze the outcome of urgent carotid endarterectomy (CEA) performed within less than six hours in patients with crescendo transient ischemic attack (TIA) and stroke in progression. From January 1998 to December 2008, 58 urgent CEAs were done for acute neurological ischemic events--46 patients with crescendo TIA and 12 patients with stroke in progression. Brain computed tomography (CT) was done prior and after the surgery. Disability level was assessed prior to and after urgent CEA using modified Rankin scale. Median follow-up was 42.1 ± 16.6 months. In the early postoperative period stroke rate was 0% for the patients in crescendo TIA group while in patients with stroke in progression group 3 patients (25%) had positive postoperative brain CT, yet neurological status significantly improved. Mid-term stroke rate was 2.2% in crescendo TIA group and 8.3% in stroke in progression group. In the early postoperative period there were no lethal outcomes, mid-term mortality was 8.3% in stroke in progression while in crescendo TIA group lethal outcomes were not observed. In conclusion, based on our results urgent CEA is a safe and effective treatment option for patients with crescendo TIA and stroke in progression with acceptable rate of postoperative complications.

  13. Acute myocardial infarction versus other cardiovascular events in community-acquired pneumonia

    PubMed Central

    Ramirez, Julio; Cosentini, Roberto; Valenti, Vincenzo; Voza, Antonio; Rossi, Paolo; Stolz, Daiana; Legnani, Delfino; Pesci, Alberto; Richeldi, Luca; Peyrani, Paula; Massari, Fernando Maria; Blasi, Francesco

    2015-01-01

    The aim of the present study was to define the prevalence, characteristics, risk factors and impact on clinical outcomes of acute myocardial infarction (AMI) versus other cardiovascular events (CVEs) in patients with community-acquired pneumonia (CAP). This was an international, multicentre, observational, prospective study of CAP patients hospitalised in eight hospitals in Italy and Switzerland. Three groups were identified: those without CVEs, those with AMI and those with other CVEs. Among 905 patients, 21 (2.3%) patients experienced at least one AMI, while 107 (11.7%) patients experienced at least one other CVE. Patients with CAP and either AMI or other CVEs showed a higher severity of the disease than patients with CAP alone. Female sex, liver disease and the presence of severe sepsis were independent predictors for the occurrence of AMI, while female sex, age >65 years, neurological disease and the presence of pleural effusion predicted other CVEs. In-hospital mortality was significantly higher among those who experienced AMI in comparison to those experiencing other CVEs (43% versus 21%, p=0.039). The presence of AMI showed an adjusted odds ratio for in-hospital mortality of 3.57 (p=0.012) and for other CVEs of 2.63 (p=0.002). These findings on AMI versus other CVEs as complications of CAP may be important when planning interventional studies on cardioprotective medications.

  14. Carotid Intima-Media Thickness Progression and Risk of Vascular Events in People With Diabetes: Results From the PROG-IMT Collaboration

    PubMed Central

    Price, Jackie F.; Robertson, Christine; Bots, Michiel L.; Polak, Joseph F.; Poppert, Holger; Kavousi, Maryam; Dörr, Marcus; Stensland, Eva; Ducimetiere, Pierre; Ronkainen, Kimmo; Kiechl, Stefan; Sitzer, Matthias; Rundek, Tatjana; Lind, Lars; Liu, Jing; Bergström, Göran; Grigore, Liliana; Bokemark, Lena; Friera, Alfonsa; Yanez, David; Bickel, Horst; Ikram, M. Arfan; Völzke, Henry; Johnsen, Stein Harald; Empana, Jean Philippe; Tuomainen, Tomi-Pekka; Willeit, Peter; Steinmetz, Helmuth; Desvarieux, Moise; Xie, Wuxiang; Schmidt, Caroline; Norata, Giuseppe D.; Suarez, Carmen; Sander, Dirk; Hofman, Albert; Schminke, Ulf; Mathiesen, Ellisiv; Plichart, Matthieu; Kauhanen, Jussi; Willeit, Johann; Sacco, Ralph L.; McLachlan, Stela; Zhao, Dong; Fagerberg, Björn; Catapano, Alberico L.; Gabriel, Rafael; Franco, Oscar H.; Bülbül, Alpaslan; Scheckenbach, Frank; Pflug, Anja; Gao, Lu; Thompson, Simon G.

    2015-01-01

    OBJECTIVE Carotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes. RESEARCH DESIGN AND METHODS In a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33–92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis. RESULTS Average mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12–1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between −0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91–1.08). CONCLUSIONS Despite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes. PMID:26180107

  15. 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

  16. Thrombotic recurrences and bleeding events in APS vascular patients: a review from the literature and a comparison with the APS Piedmont Cohort.

    PubMed

    Bazzan, M; Vaccarino, A; Stella, S; Bertero, M T; Carignola, R; Montaruli, B; Roccatello, D; Shoenfeld, Y

    2013-06-01

    In APS vascular patients, thrombotic recurrences are more frequent than in non-APS thrombotic patients. To better define this clinical setting, a systematic review of the literature after 1999 was performed: 8 cohort studies (including the recent APS Piedmont Cohort) and 6 intervention studies were selected and evaluated. Thrombotic recurrences, bleeding events, therapeutic strategies, antiphospholipid (aPL) profile, inherited and acquired risk factors (when present) were calculated and compared. Emerging risk factors for thrombotic recurrences include withdrawal of oral anticoagulant therapy (OAT), high intensity OAT (INR range 3-4), aPL profile (triple positivity, Miyakis types 1 and 2a profiles) and association with inherited or acquired pro-thrombotic risk factors. Moreover, there are evidences that high risk (mainly for aPL profile) APS vascular patients have a high recurrence rate in spite of correct OAT treatment. Clinical trials in this clinical setting are needed.

  17. Risk of Adverse Vascular Events in Newly Diagnosed Glioblastoma Multiforme Patients Treated with Bevacizumab: a Systematic Review and Meta-Analysis.

    PubMed

    Li, Xiaoqing; Huang, Rongzhong; Xu, Zhongye

    2015-01-01

    Previous evidence suggests that the humanized anti-VEGF antibody bevacizumab increases thrombosis risk in glioma patients. Here, we comprehensively assessed the risk of adverse vascular events in adult glioma patients receiving bevacizumab therapy. Systematic searches of MEDLINE, EMBASE, and the Cochrane Library were conducted to find prospective phase II/III clinical trials on adult bevacizumab-treated glioma patients and non-bevacizumab-treated controls that reported data on adverse vascular events. Four high-quality trials were finally included in the systematic review, scoring greater than or equal to 7/8 on the Newcastle-Ottawa Scale. Three trials provided sufficient data for four meta-analytical comparisons between bevacizumab-treated and control groups of newly diagnosed glioblastoma multiforme (GBM) patients: all-cause discontinuation, thrombocytopenia, deep vein thrombosis (DVT), and pulmonary embolism. None of these adverse outcomes were found to be significantly different between bevacizumab-treated and control groups (P > 0.05); however, there was a trend toward significance with regard to bevacizumab therapy and the risk of pulmonary embolism (P = 0.07). As there was a trend toward significance with regard to bevacizumab therapy and the risk of pulmonary embolism, anticoagulation may be advisable in certain newly diagnosed adult GBM patients who display a history of thromboembolism and/or more serious risk factors for thromboembolic events.

  18. Upregulation of Steroidogenic Acute Regulatory Protein by Hypoxia Stimulates Aldosterone Synthesis in Pulmonary Artery Endothelial Cells to Promote Pulmonary Vascular Fibrosis

    PubMed Central

    Maron, Bradley A.; Oldham, William M.; Chan, Stephen Y.; Vargas, Sara O.; Arons, Elena; Zhang, Ying-Yi; Loscalzo, Joseph; Leopold, Jane A.

    2014-01-01

    Background The molecular mechanism(s) regulating hypoxia-induced vascular fibrosis are unresolved. Hyperaldosteronism correlates positively with vascular remodeling in pulmonary arterial hypertension (PAH), suggesting that aldosterone may contribute to the pulmonary vasculopathy of hypoxia. The hypoxia-sensitive transcription factors c-Fos/c-Jun regulate steroidogenic acute regulatory protein (StAR), which facilitates the rate-limiting step of aldosterone steroidogenesis. We hypothesized that c-Fos/c-Jun upregulation by hypoxia activates StAR-dependent aldosterone synthesis in human pulmonary artery endothelial cells (HPAECs) to promote vascular fibrosis in PAH. Methods and Results Patients with PAH, rats with Sugen/hypoxia-PAH, and mice exposed to chronic hypoxia expressed increased StAR in remodeled pulmonary arterioles, providing a basis for investigating hypoxia-StAR signaling in HPAECs. Hypoxia (2.0% FiO2) increased aldosterone levels selectively in HPAECs, which was confirmed by liquid chromatography-mass spectrometry. Increased aldosterone by hypoxia resulted from enhanced c-Fos/c-Jun binding to the proximal activator protein (AP-1) site of the StAR promoter in HPAECs, which increased StAR expression and activity. In HPAECs transfected with StAR-siRNA or treated with the AP-1 inhibitor, SR-11302, hypoxia failed to increase aldosterone, confirming that aldosterone biosynthesis required StAR activation by c-Fos/c-Jun. The functional consequences of aldosterone were confirmed by pharmacological inhibition of the mineralocorticoid receptor with spironolactone or eplerenone, which attenuated hypoxia-induced upregulation of the fibrogenic protein connective tissue growth factor and collagen III in vitro, and decreased pulmonary vascular fibrosis to improve pulmonary hypertension in Conclusions Our findings identify autonomous aldosterone synthesis in HPAECs due to hypoxia-mediated upregulation of StAR as a novel molecular mechanism that promotes pulmonary vascular

  19. Antenatal Magnesium Sulfate Exposure and Acute Cardiorespiratory Events in Preterm Infants

    PubMed Central

    DE JESUS, Lilia C.; SOOD, Beena G.; SHANKARAN, Seetha; KENDRICK, Mr. 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, Ms. Rebecca; HALE, Ellen C.; NEWMAN, Ms. Nancy S.; BALL, Ms. M. Bethany; HIGGINS, Rosemary D.

    2014-01-01

    Objective Antenatal magnesium (anteMg) is used for tocolysis, pregnancy-induced hypertension (PIH) and neuroprotection for preterm birth. Infants exposed to anteMg are at risk for respiratory depression and resuscitation in the delivery room (DR). The study objective was to compare the risk of acute cardio-respiratory (CR) events among preterm infants exposed to anteMg and those unexposed (noMg). Study Design This was a retrospective analysis of prospective data collected in the NICHD Neonatal Research Network's Generic Database from 4/1/11 to 3/31/12. The primary outcome was DR intubation or mechanical ventilation (MV) at birth or on day 1 of life. Secondary outcomes were endotracheal MV (eMV), hypotension and other neonatal morbidities and mortality. Logistic regression analysis evaluated the risk of primary outcomes after adjustment for gestational age (GA), center, antenatal steroids (ANS) and PIH/eclampsia. Results We evaluated 1,544 infants <29 weeks GA (1,091 in anteMg group and 453 in noMg group). Mothers in the anteMg group were more likely to have higher education, PIH/eclampsia and ANS; while their infants were younger in gestation and weighed less (P<0.05). The primary outcome, mortality and neonatal morbidities were similar between groups; while eMV and hypotension were significantly less among the anteMg group compared to the noMg group. AnteMg exposure was significantly associated with decreased risk of hypotension on day 1 of life and eMV on day 3 of life in the regression analysis. Conclusion Preterm infants <29 weeks GA who were exposed to anteMg did not suffer worse CR outcomes compared to those without exposure. PMID:25046806

  20. 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. PMID:25381144

  1. 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.

  2. 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.

  3. Vascular ultrasound for atherosclerosis imaging

    PubMed Central

    de Korte, Chris L.; Hansen, Hendrik H. G.; van der Steen, Anton F. W.

    2011-01-01

    Cardiovascular disease is a leading cause of death in the Western world. Therefore, detection and quantification of atherosclerotic disease is of paramount importance to monitor treatment and possible prevention of acute events. Vascular ultrasound is an excellent technique to assess the geometry of vessel walls and plaques. The high temporal as well as spatial resolution allows quantification of luminal area and plaque size and volume. While carotid arteries can be imaged non-invasively, scanning of coronary arteries requires invasive intravascular catheters. Both techniques have already demonstrated their clinical applicability. Using linear array technology, detection of disease as well as monitoring of pharmaceutical treatment in carotid arteries are feasible. Data acquired with intravascular ultrasound catheters have proved to be especially beneficial in understanding the development of atherosclerotic disease in coronary arteries. With the introduction of vascular elastography not only the geometry of plaques but also the risk for rupture of plaques might be identified. These so-called vulnerable plaques are frequently not flow-limiting and rupture of these plaques is responsible for the majority of cerebral and cardiac ischaemic events. Intravascular ultrasound elastography studies have demonstrated a high correlation between high strain and vulnerable plaque features, both ex vivo and in vivo. Additionally, pharmaceutical intervention could be monitored using this technique. Non-invasive vascular elastography has recently been developed for carotid applications by using compound scanning. Validation and initial clinical evaluation is currently being performed. Since abundance of vasa vasorum (VV) is correlated with vulnerable plaque development, quantification of VV might be a unique tool to even prevent this from happening. Using ultrasound contrast agents, it has been demonstrated that VV can be identified and quantified. Although far from routine

  4. Hemodynamic assessment and acute pulmonary vasoreactivity testing in the evaluation of children with pulmonary vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.

    PubMed

    Apitz, Christian; Hansmann, Georg; Schranz, Dietmar

    2016-05-01

    Invasive assessment of haemodynamics (ventricular, pulmonary) and testing of acute vasoreactivity in the catheterisation laboratory remain the gold standard for the diagnosis of pulmonary hypertension (PH) and pulmonary hypertensive vascular disease. However, these measurements and the interpretation thereof are challenging due to the heterogeneous aetiology of PH in childhood and potentially confounding factors in the catheterisation laboratory. Patients with pulmonary arterial hypertension (PAH) associated with congenital heart disease who have a cardiovascular shunt need to undergo a completely different catheterisation approach than those with idiopathic PAH lacking an anatomical cardiovascular defect. Diagnostic cardiac catheterisation of children with suspected PH usually includes right and left heart catheterisation, particularly for the initial assessment (ie, at the time of diagnosis), and should be performed in experienced centres only. Here, we present graded consensus recommendations for the invasive evaluation of children with PH including those with pulmonary hypertensive vascular disease and/or ventricular dysfunction. Based on the limited published studies and our own experience we suggest a structured catheterisation protocol and two separate definitions of positive acute vasoreactivity testing (AVT): (1) AVT to assess prognosis and indication for specific PH therapy, and (2) AVT to assess operability of PAH associated with congenital heart disease. The protocol and the latter definitions may help in the systematic assessment of these patients and the interpretation of the obtained data. Beyond an accurate diagnosis in the individual patient, such a structured approach may allow systematic decision making for the initiation of a specific treatment and may assist in estimating disease progression and individual prognosis.

  5. Hemodynamic assessment and acute pulmonary vasoreactivity testing in the evaluation of children with pulmonary vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.

    PubMed

    Apitz, Christian; Hansmann, Georg; Schranz, Dietmar

    2016-05-01

    Invasive assessment of haemodynamics (ventricular, pulmonary) and testing of acute vasoreactivity in the catheterisation laboratory remain the gold standard for the diagnosis of pulmonary hypertension (PH) and pulmonary hypertensive vascular disease. However, these measurements and the interpretation thereof are challenging due to the heterogeneous aetiology of PH in childhood and potentially confounding factors in the catheterisation laboratory. Patients with pulmonary arterial hypertension (PAH) associated with congenital heart disease who have a cardiovascular shunt need to undergo a completely different catheterisation approach than those with idiopathic PAH lacking an anatomical cardiovascular defect. Diagnostic cardiac catheterisation of children with suspected PH usually includes right and left heart catheterisation, particularly for the initial assessment (ie, at the time of diagnosis), and should be performed in experienced centres only. Here, we present graded consensus recommendations for the invasive evaluation of children with PH including those with pulmonary hypertensive vascular disease and/or ventricular dysfunction. Based on the limited published studies and our own experience we suggest a structured catheterisation protocol and two separate definitions of positive acute vasoreactivity testing (AVT): (1) AVT to assess prognosis and indication for specific PH therapy, and (2) AVT to assess operability of PAH associated with congenital heart disease. The protocol and the latter definitions may help in the systematic assessment of these patients and the interpretation of the obtained data. Beyond an accurate diagnosis in the individual patient, such a structured approach may allow systematic decision making for the initiation of a specific treatment and may assist in estimating disease progression and individual prognosis. PMID:27053694

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

    PubMed Central

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

    2016-01-01

    Aim: 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. Methods: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. Results: 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′). Conclusion: 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. PMID:27014090

  7. Stressful life events preceding the acute onset of schizophrenia: a cross-national study from the World Health Organization.

    PubMed

    Day, R; Nielsen, J A; Korten, A; Ernberg, G; Dube, K C; Gebhart, J; Jablensky, A; Leon, C; Marsella, A; Olatawura, M

    1987-06-01

    This study reports on the findings from a WHO sponsored cross-national investigation of life events and schizophrenia. Data are presented from a series of 386 acutely ill schizophrenic patients selected from nine field research centers located in developing and developed countries (Aarhus, Denmark; Agra, India; Cali, Colombia; Chandigarh, India; Honolulu, USA; Ibadan, Nigeria; Nagasaki, Japan; Prague, Czechoslovakia; Rochester, USA). On a methodological level, the study demonstrates that life event methodologies originating in the developed countries can be adapted for international studies and may be used to collect reasonably reliable and comparable cross-cultural data on psychosocial factors affecting the course of schizophrenic disorders. Substantive findings replicate the results of prior studies which conclude that socioenvironmental stressors may precipitate schizophrenic attacks and such events tend to cluster in the two to three week period immediately preceding illness onset.

  8. Differential Effects of Acute Alcohol on Prepulse Inhibition and Event-Related Potentials in Adolescent and Adult Wistar Rats

    PubMed Central

    Pian, Jerry P.; Criado, Jose R.; Ehlers, Cindy L.

    2009-01-01

    Background Previous studies have demonstrated that adolescent and adult rats show differential sensitivity to many of the acute effects of alcohol. We recently reported evidence of developmental differences in the effects of acute alcohol on the cortical electroencephalogram (EEG). However, it is unclear whether developmental differences are also observed in other neurophysiological and neurobehavioral measurements known to be sensitive to alcohol exposure. The present study determined the age-related effects of acute alcohol on behavioral and event-related potential (ERP) responses to acoustic startle (AS) and prepulse inhibition (PPI). Methods Male adolescent and adult Wistar rats were implanted with cortical recording electrodes. The effects of acute alcohol (0.0, 0.75, and 1.5 g/kg) on behavioral and ERP responses to AS and PPI were assessed. Results Acute alcohol (0.75 and 1.5 g/kg) significantly reduced the behavioral and electrophysiological response to AS in adolescent and adult rats. Both 0.75 and 1.5 g/kg alcohol significantly enhanced the behavioral response to PPI in adolescent, but not in adult rats. During prepulse+pulse trials, 1.5 g/kg alcohol significantly increased the N10 pulse response in the adolescent frontal cortex. Acute alcohol (0.75 and 1.5 g/kg) also increased the N1 ERP pulse response to prepulse stimuli in frontal and parietal cortices in adult rats, but not in adolescent rats. Conclusions These data suggest that alcohol’s effect on behavioral and electrophysiological indices of AS do not differ between adults and adolescents whereas developmental stage does appear to significantly modify alcohol influenced response to PPI. PMID:18828807

  9. Do pollution time-series studies contain uncontrolled or residual confounding by risk factors for acute health events?

    PubMed

    Bukowski, John

    2008-07-01

    Acute health effects from air pollution are based largely on weak associations identified in time-series studies comparing daily air pollution levels to daily mortality. Much of this mortality is due to cardiovascular disease. Time-series studies have many potential limitations, but are not thought to be confounded by traditional cardiovascular risk factors (e.g., smoking status or hypertension) because these chronic risk factors are not obviously associated with daily pollution levels. However, acute psychobehavioral variants of these risk factors (e.g., smoking patterns and episodes of stress on any given day) are plausible confounders for the associations observed in time-series studies, given that time-series studies attempt to predict acute rather than chronic health outcomes. There is a fairly compelling literature on the strong link between cardiovascular events and daily "triggers" such as stress. Stress-related triggers are plausibly associated with daily pollution levels through surrogate stressors such as ambient temperature, daily workload, local traffic congestion, or other correlates of air pollution. For example, variables such as traffic congestion and industrial activity increase both stress-related health events and air pollution, suggesting the potential for classical confounding. Support for this argument is illustrated through examples of the well-demonstrated relationship between emotional stress and heart attack/stroke.

  10. Serum levels of thrombomodulin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin in the acute phase of Plasmodium vivax malaria.

    PubMed

    Ohnishi, K

    1999-02-01

    Elevated plasma or serum levels of thrombomodulin (TM), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin have been reported in several diseases. However, plasma or serum levels of TM, ICAM-1, VCAM-1, and E-selectin have not been investigated in the acute phase of Plasmodium vivax malaria. Serum TM, ICAM-1, VCAM-1, E-selectin, and creatinine levels were determined in six Japanese patients in the acute phase of vivax malaria and in seven healthy Japanese controls. Parasitemias of the peripheral blood were < 0.1% in five patients and 0.8% in one patient. The patients' mean +/- SD serum levels of TM, ICAM-1, VCAM-1, and E-selectin were 5.7 +/- 1.3 Fujirebio units/ml, 709 +/- 397 ng/ml, 2,112 +/- 782 ng/ml, and 99 +/- 28 ng/ml, respectively, and all were significantly greater than those in the controls (TM; P < 0.005, ICAM-1; P < 0.025, VCAM-1; P < 0.005, E-selectin; P < 0.025). However, no significant difference was identified between patients and controls for serum creatinine values. The serum levels of TM and VCAM-1 were not related to parasitemia. The elevation of serum TM levels suggests that endothelial cell damage occurs in the acute phase of vivax malaria.

  11. Catechol-O-Methyltransferase Gene Polymorphism Modifies the Effect of Coffee Intake on Incidence of Acute Coronary Events

    PubMed Central

    Happonen, Pertti; Voutilainen, Sari; Tuomainen, Tomi-Pekka; Salonen, Jukka T.

    2006-01-01

    Background The role of coffee intake as a risk factor for coronary heart disease (CHD) has been debated for decades. We examined whether the relationship between coffee intake and incidence of CHD events is dependent on the metabolism of circulating catecholamines, as determined by functional polymorphism of the catechol-O-methyltransferase (COMT) gene. Methodology/Principal Findings In a cohort of 773 men who were 42 to 60 years old and free of symptomatic CHD at baseline in 1984–89, 78 participants experienced an acute coronary event during an average follow-up of 13 years. In logistic regression adjusting for age, smoking, family history of CHD, vitamin C deficiency, blood pressure, plasma cholesterol concentration, and diabetes, the odds ratio (90% confidence interval) comparing heavy coffee drinkers with the low activity COMT genotype with those with the high activity or heterozygotic genotypes was 3.2 (1.2–8.4). Urinary adrenaline excretion increased with increasing coffee intake, being over two-fold in heavy drinkers compared with nondrinkers (p = 0.008 for trend). Conclusions/Significance Heavy coffee consumption increases the incidence of acute coronary events in men with low but not high COMT activity. Further studies are required to determine to which extent circulating catecholamines mediate the relationship between coffee intake and CHD. PMID:17205121

  12. 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

  13. Event-free survival and cost-effectiveness in adult acute lymphoblastic leukaemia in first remission treated with allogeneic transplantation.

    PubMed

    Orsi, C; Bartolozzi, B; Messori, A; Bosi, A

    2007-10-01

    Allogeneic transplantation in patients with acute lymphoblastic leukaemia in first remission (ALL-CR1) has been studied in several clinical trials. However, no pooled survival analysis has yet been done. We conducted a survival meta-analysis to compare allogeneic transplantation vs chemotherapy or autologous transplantation using an intention-to-treat approach. Our study included the controlled clinical trials, wherein allocation to allogeneic transplant was based on donor availability. The event-free individual survival data were reconstructed on the basis of published information and Kaplan-Meier graphs. We then generated the meta-analytic event-free survival curves for the two treatments. The mean survival gain per patient was estimated and a simplified cost-effectiveness assessment was carried out. In the allogeneic transplantation group, 293 patients were examined and 479 as controls (four trials). The event-free survival difference was statistically significant (P=0.011). The relative risk for event occurrence was 0.79 for the experimental group vs the controls (95% CI: 0.66-0.96; P=0.017). The mean survival gain was 1 year per patient. The cost per life-year gained was less than the conventional threshold of 50,000 euros. Allogeneic transplantation in ALL-CR1 improves event-free survival as compared to chemotherapy or autologous transplantation. Its cost-effectiveness profile is acceptable. PMID:17660839

  14. Relationship between Inflammatory Markers and New Cardiovascular Events in Patients with Acute Myocardial Infarction Who Underwent Primary Angioplasty

    PubMed Central

    Franca, Eluisa La; Caruso, Marco; Sansone, Angela; Iacona, Rosanna; Ajello, Laura; Mancuso, Dario; Castellano, Fabiana; Novo, Salvatore; Assennato, Pasquale

    2013-01-01

    Introduction: The determination of inflammation markers in circulation has enabled an important improvement in the study of cardiovascular diseases. It was tested the hypothesis that non-specific markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and fibrinogen may provide prognostic information in patients with acute myocardial infarction with persistent ST-segment elevation (STEMI) undergoing primary angioplasty (PCI). Methods: Patients: A cohort of 197 consecutive patients with STEMI undergoing primary PCI was enrolled, evaluating during hospitalization, the peak values of the following markers of inflammation: ESR, CRP and fibrinogen. A telephone follow-up has been made in order to investigate any possible new cardiovascular events after hospital discharge and the procedure performed. Results: Higher values of CRP were statistically associated with adverse future events as composite endpoint and with the single endpoint of death. Furthermore, higher age, presence of hypertension, history of previous cardiovascular events, were statistically significantly associated with cardiac events at follow up. In this group were also overrepresented subjects with anterior myocardial infarction in the anterior localization and with an EF ≤ 35% at discharge. Conclusions: CRP appears to be a predictor of future cardiovascular events, confirming that a pro-inflammatory state promotes the progression of atherosclerotic disease and its complications. PMID:23777720

  15. Promoting inflammatory lymphangiogenesis by vascular endothelial growth factor-C (VEGF-C) aggravated intestinal inflammation in mice with experimental acute colitis

    PubMed Central

    Wang, X.L.; Zhao, J.; Qin, L.; Qiao, M.

    2016-01-01

    Angiogenesis and lymphangiogenesis are thought to play a role in the pathogenesis of inflammatory bowel diseases (IBD). However, it is not understood if inflammatory lymphangiogenesis is a pathological consequence or a productive attempt to resolve the inflammation. This study investigated the effect of lymphangiogenesis on intestinal inflammation by overexpressing a lymphangiogenesis factor, vascular endothelial growth factor-C (VEGF-C), in a mouse model of acute colitis. Forty eight-week-old female C57BL/6 mice were treated with recombinant adenovirus overexpressing VEGF-C or with recombinant VEGF-C156S protein. Acute colitis was then established by exposing the mice to 5% dextran sodium sulfate (DSS) for 7 days. Mice were evaluated for disease activity index (DAI), colonic inflammatory changes, colon edema, microvessel density, lymphatic vessel density (LVD), and VEGFR-3mRNA expression in colon tissue. When acute colitis was induced in mice overexpressing VEGF-C, there was a significant increase in colonic epithelial damage, inflammatory edema, microvessel density, and neutrophil infiltration compared to control mice. These mice also exhibited increased lymphatic vessel density (73.0±3.9 vs 38.2±1.9, P<0.001) and lymphatic vessel size (1974.6±104.3 vs 1639.0±91.5, P<0.001) compared to control mice. Additionally, the expression of VEGFR-3 mRNA was significantly upregulated in VEGF-C156S mice compared to DSS-treated mice after induction of colitis (42.0±1.4 vs 3.5±0.4, P<0.001). Stimulation of lymphangiogenesis by VEGF-C during acute colitis promoted inflammatory lymphangiogenesis in the colon and aggravated intestinal inflammation. Inflammatory lymphangiogenesis may have pleiotropic effects at different stages of IBD. PMID:27074165

  16. 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

  17. Post-Acute Care Services Received by Older Adults Following a Cardiac Event: A Population-Based Analysis

    PubMed Central

    Xu, Fang; Zullo, Melissa; Shishehbor, Mehdi; Moore, Shirley M.; Rimm, Alfred A.

    2010-01-01

    Background Post-acute care (PAC) is available for older adults who need additional services after hospitalization for acute cardiac events. With the aging population and an increase in the prevalence of cardiac disease, it is important to determine current PAC use for cardiac patients to assist health care workers to meet the needs of older cardiac patients. The purpose of this study was to determine the current PAC use and factors associated with PAC use for older adults following hospitalization for a cardiac event that includes coronary artery bypass graph (CABG) and valve surgeries, myocardial infarction (MI), percutaneous coronary intervention (PCI), and heart failure (HF). Methods and Results A cross-sectional design and the 2003 Medicare Part A database were used for this study. The sample (n=1,493,521) consisted of patients aged 65 years and older discharged after their first cardiac event. Multinomial logistic regression was used to examine factors associated with PAC use. Overall, PAC use was 55% for cardiac valve surgery, 50% for MI, 45% for HF, 44% for CABG, and 5% for PCI. Medical patients use more skilled nursing facility care and surgical patients use more home health care. Only 0.1–3.4% of the cardiac patients use intermediate rehabilitation facilities. Compared to those who do not use PAC, those who use home health care and skilled nursing facility care are older, female, have a longer hospital length of stay, and more comorbidity. Asians, Hispanics and Native Americans were less likely to use PAC after hospitalization for an MI or HF. Conclusions The current rate of PAC use indicates that almost half of non-disabled Medicare patients discharged from the hospital following a cardiac event use one of these services. Healthcare professionals can increase PAC use for Asians, Hispanics and Native Americans by including culturally targeted communication. Optimizing recovery for cardiac patients who use PAC may require focused cardiac rehabilitation

  18. Factor XIa and Thrombin Generation Are Elevated in Patients with Acute Coronary Syndrome and Predict Recurrent Cardiovascular Events

    PubMed Central

    Loeffen, Rinske; van Oerle, René; Leers, Mathie P. G.; Kragten, Johannes A.; Crijns, Harry; Spronk, Henri M. H.; ten Cate, Hugo

    2016-01-01

    Objective In acute coronary syndrome (ACS) cardiac cell damage is preceded by thrombosis. Therefore, plasma coagulation markers may have additional diagnostic relevance in ACS. By using novel coagulation assays this study aims to gain more insight into the relationship between the coagulation system and ACS. Methods We measured plasma thrombin generation, factor XIa and D-dimer levels in plasma from ACS (n = 104) and non-ACS patients (n = 42). Follow-up measurements (n = 73) were performed at 1 and 6 months. Associations between coagulation markers and recurrent cardiovascular events were calculated by logistic regression analysis. Results Thrombin generation was significantly enhanced in ACS compared to non-ACS patients: peak height 148±53 vs. 122±42 nM. There was a significantly diminished ETP reduction (32 vs. 41%) and increased intrinsic coagulation activation (25 vs. 7%) in ACS compared to non-ACS patients. Furthermore, compared to non-ACS patients factor XIa and D-dimer levels were significantly elevated in ACS patients: 1.9±1.1 vs. 1.4±0.7 pM and 495(310–885) vs. 380(235–540) μg/L. Within the ACS spectrum, ST-elevated myocardial infarction patients had the highest prothrombotic profile. During the acute event, thrombin generation was significantly increased compared to 1 and 6 months afterwards: peak height 145±52 vs. 100±44 vs. 98±33 nM. Both peak height and factor XIa levels on admission predicted recurrent cardiovascular events (OR: 4.9 [95%CI 1.2–20.9] and 4.5 [1.1–18.9]). Conclusion ACS patients had an enhanced prothrombotic profile, demonstrated by an increased thrombin generation potential, factor XIa and D-dimer levels. This study is the first to demonstrate the positive association between factor XIa, thrombin generation and recurrent cardiovascular events. PMID:27419389

  19. 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

  20. Metabolic disease in 10 patients with sudden unexpected death in infancy or acute life-threatening events.

    PubMed

    Takahashi, Tomoo; Yamada, Kenji; Kobayashi, Hironori; Hasegawa, Yuki; Taketani, Takeshi; Fukuda, Seiji; Yamaguchi, Seiji

    2015-06-01

    In order to determine the associations between sudden unexpected death in infancy (SUDI) or acute life-threatening events (ALTE) and inborn errors of metabolism, particularly organic acidemia and fatty acid oxidation disorders, we evaluated clinical features in patients with SUDI or ALTE. The subjects were infants between the ages of 7 days and 3 years who developed SUDI or ALTE between January 2004 and December 2013. They were then diagnosed as having inborn errors of metabolism on gas chromatography-mass spectrometry (GC/MS) and/or tandem mass spectrometry (MS/MS). The age distribution, onset forms, and clinical findings were evaluated during the acute phase. Inborn errors of metabolism were detected in three of 196 patients with SUDI, and in seven of 167 patients with ALTE. Of these 10 patients, nine had a history of poor feeding and somnolence during the neonatal period, and symptoms of infection such as cough, fever or vomiting during infancy. Routine laboratory tests during an acute phase indicated hyperammonemia, liver dysfunction, increased blood creatine kinase, acidosis, positive ketone bodies in urine or blood, or hypoglycemia. When SUDI or ALTE are encountered in the emergency unit, it is essential that a detailed medical history is taken, particularly with regard to the neonatal period, and that specific abnormalities are investigated on routine laboratory tests. Moreover, samples such as urine, serum, and filter paper blood specimens should be collected for GC/MS and/or MS/MS of organic acids and acylcarnitines, to identify inborn metabolic disorders.

  1. Use of embolic protective devices in treating acute arterial occlusions: an interventional radiology and vascular surgery collaborative learning experience

    PubMed Central

    Woodley-Cook, Joel; Prabhudesai, Vikram; Moloney, Tony

    2013-01-01

    A 43-year-old man presented to the emergency department with left leg claudication. CT angiogram confirmed an acute left leg arterial occlusion from a left ventricular thrombus. During intra-arterial thrombolysis, he developed severe abdominal pain and a CT angiogram confirmed an acute occlusive thromboembolism to his left renal artery. Prior to left renal artery intra-arterial embolectomy, temporary intra-arterial occlusion balloons were inflated within his (1) right renal artery to protect this kidney from acute embolism and (2) left iliac artery to protect his left leg from further clot burden. Following the left renal embolectomy, an angiogram demonstrated patent renal arteries, acute occlusion of the right common iliac artery and persistent clot in his left iliac/lower limb. These occlusions were retrieved by surgical embolectomy. Final angiogram demonstrated patent bilateral iliac/lower limb arteries. The patient was discharged on lifelong anticoagulation and remains asymptomatic with bilateral palpable distal pulses and normal serum creatine. PMID:23580669

  2. Acute deep brain stimulation in the thalamic reticular nucleus protects against acute stress and modulates initial events of adult hippocampal neurogenesis.

    PubMed

    Magdaleno-Madrigal, Víctor Manuel; Pantoja-Jiménez, Christopher Rodrigo; Bazaldúa, Adrián; Fernández-Mas, Rodrigo; Almazán-Alvarado, Salvador; Bolaños-Alejos, Fernanda; Ortíz-López, Leonardo; Ramírez-Rodriguez, Gerardo Bernabé

    2016-11-01

    Deep brain stimulation (DBS) is used as an alternative therapeutic procedure for pharmacoresistant psychiatric disorders. Recently the thalamic reticular nucleus (TRN) gained attention due to the description of a novel pathway from the amygdala to this nucleus suggesting that may be differentially disrupted in mood disorders. The limbic system is implicated in the regulation of these disorders that are accompanied by neuroplastic changes. The hippocampus is highly plastic and shows the generation of new neurons, process affected by stress but positively regulated by antidepressant drugs. We explored the impact of applying acute DBS to the TRN (DBS-TRN) in male Wistar rats exposed to acute stress caused by the forced-swim Porsolt's test (FST) and on initial events of hippocampal neurogenesis. After the first session of forced-swim, rats were randomly subdivided in a DBS-TRN and a Sham group. Stimulated rats received 10min of DBS, thus the depressant-like behavior reflected as immobility was evaluated in the second session of forced-swim. Locomotricity was evaluated in the open field test. Cell proliferation and doublecortin-associated cells were quantified in the hippocampus of other cohorts of rats. No effects of electrode implantation were found in locomotricity. Acute DBS-TRN reduced immobility in comparison to the Sham group (p<0.001). DBS-TRN increased cell proliferation (Ki67 or BrdU-positive cells; p=0.02, p=0.02) and the number of doublecortin-cells compared to the Sham group (p<0.02). Similar effects were found in rats previously exposed to the first session of forced-swim. Our data could suggest that TRN brain region may be a promising target for DBS to treat intractable depression.

  3. Acute deep brain stimulation in the thalamic reticular nucleus protects against acute stress and modulates initial events of adult hippocampal neurogenesis.

    PubMed

    Magdaleno-Madrigal, Víctor Manuel; Pantoja-Jiménez, Christopher Rodrigo; Bazaldúa, Adrián; Fernández-Mas, Rodrigo; Almazán-Alvarado, Salvador; Bolaños-Alejos, Fernanda; Ortíz-López, Leonardo; Ramírez-Rodriguez, Gerardo Bernabé

    2016-11-01

    Deep brain stimulation (DBS) is used as an alternative therapeutic procedure for pharmacoresistant psychiatric disorders. Recently the thalamic reticular nucleus (TRN) gained attention due to the description of a novel pathway from the amygdala to this nucleus suggesting that may be differentially disrupted in mood disorders. The limbic system is implicated in the regulation of these disorders that are accompanied by neuroplastic changes. The hippocampus is highly plastic and shows the generation of new neurons, process affected by stress but positively regulated by antidepressant drugs. We explored the impact of applying acute DBS to the TRN (DBS-TRN) in male Wistar rats exposed to acute stress caused by the forced-swim Porsolt's test (FST) and on initial events of hippocampal neurogenesis. After the first session of forced-swim, rats were randomly subdivided in a DBS-TRN and a Sham group. Stimulated rats received 10min of DBS, thus the depressant-like behavior reflected as immobility was evaluated in the second session of forced-swim. Locomotricity was evaluated in the open field test. Cell proliferation and doublecortin-associated cells were quantified in the hippocampus of other cohorts of rats. No effects of electrode implantation were found in locomotricity. Acute DBS-TRN reduced immobility in comparison to the Sham group (p<0.001). DBS-TRN increased cell proliferation (Ki67 or BrdU-positive cells; p=0.02, p=0.02) and the number of doublecortin-cells compared to the Sham group (p<0.02). Similar effects were found in rats previously exposed to the first session of forced-swim. Our data could suggest that TRN brain region may be a promising target for DBS to treat intractable depression. PMID:27435420

  4. Validity of the GRACE (Global Registry of Acute Coronary Events) acute coronary syndrome prediction model for six month post‐discharge death in an independent data set

    PubMed Central

    Bradshaw, P J; Ko, D T; Newman, A M; Donovan, L R

    2006-01-01

    Objective To determine the validity of the GRACE (Global Registry of Acute Coronary Events) prediction model for death six months after discharge in all forms of acute coronary syndrome in an independent dataset of a community based cohort of patients with acute myocardial infarction (AMI). Design Independent validation study based on clinical data collected retrospectively for a clinical trial in a community based population and record linkage to administrative databases. Setting Study conducted among patients from the EFFECT (enhanced feedback for effective cardiac treatment) study from Ontario, Canada. Patients Randomly selected men and women hospitalised for AMI between 1999 and 2001. Main outcome measure Discriminatory capacity and calibration of the GRACE prediction model for death within six months of hospital discharge in the contemporaneous EFFECT AMI study population. Results Post‐discharge crude mortality at six months for the EFFECT study patients with AMI was 7.0%. The discriminatory capacity of the GRACE model was good overall (C statistic 0.80) and for patients with ST segment elevation AMI (STEMI) (0.81) and non‐STEMI (0.78). Observed and predicted deaths corresponded well in each stratum of risk at six months, although the risk was underestimated by up to 30% in the higher range of scores among patients with non‐STEMI. Conclusions In an independent validation the GRACE risk model had good discriminatory capacity for predicting post‐discharge death at six months and was generally well calibrated, suggesting that it is suitable for clinical use in general populations. PMID:16387810

  5. Cancer Events After Acute or Chronic Exposure to Sulfur Mustard: A Review of the Literature

    PubMed Central

    Razavi, Seyed Mansour; Abdollahi, Mohammad; Salamati, Payman

    2016-01-01

    Background: Sulfur mustard (SM) has been considered as a carcinogen in the laboratory studies. However, its carcinogenic effects on human beings were not well discussed. The main purpose of our study is to assess carcinogenesis of SM following acute and/or chronic exposures in human beings. Methods: The valid scientific English and Persian databases including PubMed, Web of Science, Scopus, IranMedex, and Irandoc were searched and the collected papers reviewed. The used keywords were in two languages: English and Persian. The inclusion criteria were the published original articles indexed in above-mentioned databases. Eleven full-texts out of 296 articles were found relevant and then assessed. Results: Studies on the workers of the SM factories during the World Wars showed that the long-term chronic exposure to mustards can cause a variety of cancers in the organs such as oral cavity, larynx, lung, and skin. Respiratory system was the most important affected system. Acute single exposure to SM was assumed as the carcinogenic inducer in the lung and blood and for few cancers including basal cell carcinoma and squamous cell carcinoma. Conclusions: SM is a proven carcinogen in chronic situations although data are not enough to strongly conclude in acute exposure. PMID:27280012

  6. Effect of acute hyaluronidase treatment of the glycocalyx on tracer-based whole body vascular volume estimates in mice.

    PubMed

    VanTeeffelen, Jurgen W G E; Brands, Judith; Janssen, Ben J A; Vink, Hans

    2013-05-01

    The endothelial glycocalyx forms a hyaluronan-containing interface between the flowing blood and the endothelium throughout the body. By comparing the systemic distribution of a small glycocalyx-accessible tracer vs. a large circulating plasma tracer, the size-selective barrier properties of the glycocalyx have recently been utilized to estimate whole body glycocalyx volumes in humans and animals, but a comprehensive validation of this approach has been lacking at the moment. In the present study, we compared, in anesthetized, ventilated C57Bl/6 mice, the whole body distribution of small (40 kDa) dextrans (Texas Red labeled; Dex40) vs. that of intermediate (70 kDa) and large (500 kDa) dextrans (both FITC labeled; Dex70 and Dex500, respectively) using tracer dilution and vs. that of circulating plasma, as derived from the dilution of fluorescein-labeled red blood cells and large-vessel hematocrit. The contribution of the glycocalyx was evaluated by intravenous infusion of a bolus of the enzyme hyaluronidase. In saline-treated control mice, distribution volume (in ml) differed between tracers (P < 0.05; ANOVA) in the following order: Dex40 (0.97 ± 0.04) > Dex70 (0.90 ± 0.04) > Dex500 (0.81 ± 0.10) > plasma (0.71 ± 0.02), resulting in an inaccessible vascular volume, i.e., compared with the distribution volume of Dex40, of 0.03 ± 0.01, 0.15 ± 0.04, and 0.31 ± 0.05 ml for Dex70, Dex500, and plasma, respectively. In hyaluronidase-treated mice, Dex70 and Dex40 volumes were not different from each other, and inaccessible vascular volumes for Dex500 (0.03 ± 0.03) and plasma (0.14 ± 0.05) were smaller (P < 0.05) than those in control animals. Clearance of Dex70 and Dex500 from the circulation was enhanced (P < 0.05) in hyaluronidase-treated vs. control mice. These results indicate that the glycocalyx contributes to size-dependent differences in whole body vascular distribution of plasma solutes in mice. Whole body vascular volume measurements based on the

  7. Effect of acute hyaluronidase treatment of the glycocalyx on tracer-based whole body vascular volume estimates in mice.

    PubMed

    VanTeeffelen, Jurgen W G E; Brands, Judith; Janssen, Ben J A; Vink, Hans

    2013-05-01

    The endothelial glycocalyx forms a hyaluronan-containing interface between the flowing blood and the endothelium throughout the body. By comparing the systemic distribution of a small glycocalyx-accessible tracer vs. a large circulating plasma tracer, the size-selective barrier properties of the glycocalyx have recently been utilized to estimate whole body glycocalyx volumes in humans and animals, but a comprehensive validation of this approach has been lacking at the moment. In the present study, we compared, in anesthetized, ventilated C57Bl/6 mice, the whole body distribution of small (40 kDa) dextrans (Texas Red labeled; Dex40) vs. that of intermediate (70 kDa) and large (500 kDa) dextrans (both FITC labeled; Dex70 and Dex500, respectively) using tracer dilution and vs. that of circulating plasma, as derived from the dilution of fluorescein-labeled red blood cells and large-vessel hematocrit. The contribution of the glycocalyx was evaluated by intravenous infusion of a bolus of the enzyme hyaluronidase. In saline-treated control mice, distribution volume (in ml) differed between tracers (P < 0.05; ANOVA) in the following order: Dex40 (0.97 ± 0.04) > Dex70 (0.90 ± 0.04) > Dex500 (0.81 ± 0.10) > plasma (0.71 ± 0.02), resulting in an inaccessible vascular volume, i.e., compared with the distribution volume of Dex40, of 0.03 ± 0.01, 0.15 ± 0.04, and 0.31 ± 0.05 ml for Dex70, Dex500, and plasma, respectively. In hyaluronidase-treated mice, Dex70 and Dex40 volumes were not different from each other, and inaccessible vascular volumes for Dex500 (0.03 ± 0.03) and plasma (0.14 ± 0.05) were smaller (P < 0.05) than those in control animals. Clearance of Dex70 and Dex500 from the circulation was enhanced (P < 0.05) in hyaluronidase-treated vs. control mice. These results indicate that the glycocalyx contributes to size-dependent differences in whole body vascular distribution of plasma solutes in mice. Whole body vascular volume measurements based on the

  8. Acute clinical events in 299 homozygous sickle cell patients living in France. French Study Group on Sickle Cell Disease.

    PubMed

    Neonato, M G; Guilloud-Bataille, M; Beauvais, P; Bégué, P; Belloy, M; Benkerrou, M; Ducrocq, R; Maier-Redelsperger, M; de Montalembert, M; Quinet, B; Elion, J; Feingold, J; Girot, R

    2000-09-01

    A subset of 299 patients with homozygous sickle cell anaemia, enrolled in the cohort of the French Study Group on sickle cell disease (SCD), was investigated in this study. The majority of patients were children (mean age 10.1 +/- 5.8 yr) of first generation immigrants from Western and Central Africa, the others originated from the French West Indies (20.2%). We report the frequency of the main clinical events (mean follow-up 4.2 +/- 2.2 yr). The prevalence of meningitis-septicaemia and osteomyelitis was, respectively, 11.4% and 12% acute chest syndrome was observed in 134 patients (44.8%). Twenty patients (6.7%) developed stroke with peak prevalence at 10-15 yr of age. One hundred and seventy-two patients (58%) suffered from one or more painful sickle cell crises, while the others (42.5%) never suffered from pain. The overall frequency of acute anaemic episodes was 50.5%, (acute aplastic anaemia 46%; acute splenic sequestration 26%). A group of 27 patients were asymptomatic (follow-up > 3 yr). Epistatic mechanisms influencing SCD were studied. Coinherited alpha-thalassemia strongly reduced the risk of stroke (p <0.001) and increased that of painful crises (p < 0.02). There was a low prevalence of Senegal and Bantu (CAR) betas-chromosomes in patients with meningitis (p <0.04) and osteomyelitis (p < 0.03). Prevalence of Senegal betas-chromosomes was lower in the asymptomatic group of 27 patients (p < 0.02). The patients come from a population of unmixed immigrants in whom the beta-globin gene haplotype strongly reflects the geographic origin and identifies subgroups with a homogenous genetic background. Thus the observed effects might result more from differences in as yet unidentified determinants in the genetic background than from the direct linkage with differences in the beta-globin gene locus.

  9. Real-life comparison of severe vascular events and other non-hematological complications in patients with chronic myeloid leukemia undergoing second-line nilotinib or dasatinib treatment.

    PubMed

    Gora-Tybor, Joanna; Medras, Ewa; Calbecka, Malgorzata; Kolkowska-Leśniak, Agnieszka; Ponikowska-Szyba, Edyta; Robak, Tadeusz; Jamroziak, Krzysztof

    2015-01-01

    We retrospectively analyzed the rates of significant non-hematological adverse events (AEs) in 105 patients with chronic myeloid leukemia (CML) treated with second-generation tyrosine kinase inhibitor (TKIs) dasatinib or nilotinib used as second-line therapy in Polish tertiary care centers. Our analysis revealed that in a "real life setting," nearly half of patients with CML on second-generation TKIs suffer from therapy complications. Grade 2-5 non-hematological AEs were observed in 40% of patients treated with nilotinib and in 42% treated with dasatinib (p=0.83). Severe vascular events including peripheral artery occlusive disease (PAOD) occurred in 11% of patients on nilotinib and 4% on dasatinib (p=0.16). Pleural effusion occurred more often in the dasatinib group (26%) than in the nilotinib group (2%) (p=0.003). Importantly, most AEs occurred late, after more than 1 year of treatment. Since AEs are most often the reason for poor therapy compliance, careful monitoring of tolerability is crucial for an optimal treatment response in CML.

  10. 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. PMID:27612952

  11. Vascular calcification on plain radiographs is associated with carotid intima media thickness, malnutrition and cardiovascular events in dialysis patients: a prospective observational study

    PubMed Central

    2013-01-01

    Background Vascular calcification (VC) and carotid intima media thickness (CIMT) are strongly associated with cardiovascular (CV) disease. We hypothesized that significant VC on plain radiographs is associated with CIMT and CV events in dialysis patients. In addition, we evaluated risk factors for VC progression on plain radiographs in dialysis patients. Methods In this 2-year observational, prospective study, 67 dialysis patients were included. We checked plain radiographs at baseline and after 2 years. Laboratory tests and malnutrition score were obtained at baseline, after 12 months, and after 24 months. Results The mean age of patients was 56.3 ± 10.3 years and duration of dialysis was 41.3 ± 34.5 months. The prevalence of significant VC was 61.2% and the prevalence of carotid artery atheromatous plaques was 55.6%. Mean CIMT, malnutrition scores, CRP level and prevalence of carotid atheromatous plaques were significantly higher in patients with significant VC. Serum albumin and total iron binding capacity were significantly lower in patients with significant VC compared to patients without significant VC. During a mean observational period of 22 months, patients without significant VC showed lower CV events by the Kaplan-Meyer method (p = 0.010). Progression of VC was found in 35.7% among 56 patients followed up. Hemoglobin after 24 months was an independent factor for progression of VC (Exp(B) = 0.344, 95% Confidence Interval = 0.13 – 0.96, p = 0.034). Conclusions Significant VC on plain radiograph was associated with CIMT, malnutrition, inflammation, and CV events in dialysis patients. Conditions which increase hemoglobin level may retard progression of VC in dialysis patients. PMID:23360132

  12. 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

  13. Acute Effects of Asian Dust Events on Respiratory Symptoms and Peak Expiratory Flow in Children with Mild Asthma

    PubMed Central

    Yoo, Young; Choung, Ji Tae; Yu, Jinho; Kim, Do Kyun

    2008-01-01

    The aim of this study was to investigate the possible adverse effects of Asian dust events on respiratory health in asthmatic children. Fifty-two children with mild asthma were studied for eight consecutive weeks in the spring of 2004 (March 8 to May 2). During the study period, five Asian dust days were identified; we included a lag period of two days following each of the events. Subjects recorded their respiratory symptom diaries and peak expiratory flow (PEF) twice daily during the study period; and they underwent methacholine bronchial challenge tests. The subjects reported a significantly higher frequency of respiratory symptoms during the Asian dust days than during the control days. They showed significantly more reduced morning and evening PEF values, and more increased PEF variability (10.1%±3.5% vs. 5.5%±2.2%) during the Asian dust days than during the control days. Methacholine PC20 was not significantly different between before and after the study period (geometric mean: 2.82 mg/mL vs. 3.16 mg/mL). These results suggest that the short-term Asian dust events might be associated with increased acute respiratory symptoms and changes in PEF outcomes. However, there might be little long-term influence on airway hyperresponsiveness in children with mild asthma. PMID:18303201

  14. Effects of acute low-temperature events on development of Erysiphe necator and susceptibility of Vitis vinifera.

    PubMed

    Moyer, Michelle M; Gadoury, David M; Cadle-Davidson, Lance; Dry, Ian B; Magarey, Peter A; Wilcox, Wayne F; Seem, Robert C

    2010-11-01

    Growth and development of Erysiphe necator (syn. Uncinula necator) has been extensively studied under controlled conditions, primarily with a focus on development of grapevine powdery mildew within the optimal temperature range and the lethal effects of high temperatures. However, little is known of the effect of cold temperatures (above freezing but <8 degrees C) on pathogen development or host resistance. Pretreatment of susceptible Vitis vinifera leaf tissue by exposure to cold temperatures (2 to 8 degrees C for 2 to 8 h) reduced infection efficiency and colony expansion when tissues were subsequently inoculated. Furthermore, nascent colonies exposed to similar cold events exhibited hyphal mortality, reduced expansion, and increased latent periods. Historical weather data and an analysis of the radiational cooling of leaf tissues in the field indicated that early-season cold events capable of inducing the foregoing responses occur commonly and frequently across many if not most viticultural regions worldwide. These phenomena may partially explain (i) the unexpectedly slow development of powdery mildew during the first month after budbreak in some regions and (ii) the sudden increase in epidemic development once seasonal temperatures increase above the threshold for acute cold events. PMID:20649419

  15. Vascular Lesions.

    PubMed

    Jahnke, Marla N

    2016-08-01

    Vascular lesions in childhood are comprised of vascular tumors and vascular malformations. Vascular tumors encompass neoplasms of the vascular system, of which infantile hemangiomas (IHs) are the most common. Vascular malformations, on the other hand, consist of lesions due to anomalous development of the vascular system, including the capillary, venous, arterial, and lymphatic systems. Capillary malformations represent the most frequent type of vascular malformation. IHs and vascular malformations tend to follow relatively predictable growth patterns in that IHs grow then involute during early childhood, whereas vascular malformations tend to exhibit little change. Both vascular tumors and vascular malformations can demonstrate a wide range of severity and potential associated complications necessitating specialist intervention when appropriate. Evaluation and treatment of the most common types of vascular lesions are discussed in this article. [Pediatr Ann. 2016;45(8):e299-e305.]. PMID:27517358

  16. Implementing emergency manuals: can cognitive aids help translate best practices for patient care during acute events?

    PubMed

    Goldhaber-Fiebert, Sara N; Howard, Steven K

    2013-11-01

    In this article, we address whether emergency manuals are an effective means of helping anesthesiologists and perioperative teams apply known best practices for critical events. We review the relevant history of such cognitive aids in health care, as well as examples from other high stakes industries, and describe why emergency manuals have a role in improving patient care during certain events. We propose 4 vital elements: create, familiarize, use, and integrate, necessary for the widespread, successful development, and implementation of medical emergency manuals, using the specific example of the perioperative setting. The details of each element are presented, drawing from the medical literature as well as from our combined experience of more than 30 years of observing teams of anesthesiologists managing simulated and real critical events. We emphasize the importance of training clinicians in the use of emergency manuals for education on content, format, and location. Finally, we discuss cultural readiness for change, present a system example of successful integration, and highlight the importance of further research on the implementation of emergency manuals.

  17. [Vascular Ehlers-Danlos syndrome].

    PubMed

    Frank, Michael

    2009-04-20

    Vascular type Ehlers-Danlos syndrome (EDS) is a rare inherited disease with an autosomal dominant trait. The mutation of the COL3A1 gene which encodes type III collagen, is responsible of early vascular (spontaneous arterial rupture or dissection), digestive (perforation) and obstetrical events (uterine and arterial rupture). Diagnosis of the disease is primarily clinical, especially in case of characteristic morphologic features. Diagnostic certainty is obtained by evidencing the mutation of the COL3A1 gene. Some arterial lesions are suggestive of the disease, as dissecting aneurysms of the internal carotid, of the iliac arteries, and of the anterior visceral aortic branches, fusiform aneurisms of the splenic artery, and the occurrence of a non traumatic direct carotid-cavernous fistula. The occurrence of a spontaneous peritonitis or of an extensive perineal tear after delivery should also draw physician's attention. Because of the unpredictability of arterial or organ rupture, any patient diagnosed with vascular type EDS presenting with an acute pain syndrome should be considered as a trauma situation and be investigated straightaway by CT-scan or MRI testing, in order to eliminate a life threatening complication. PMID:19462862

  18. Effects of Ocean Acidification on the Brown Alga Padina pavonica: Decalcification Due to Acute and Chronic Events

    PubMed Central

    Gil-Díaz, Teba; Haroun, Ricardo; Tuya, Fernando; Betancor, Séfora; Viera-Rodríguez, María A.

    2014-01-01

    Since the industrial revolution, anthropogenic CO2 emissions have caused ocean acidification, which particularly affects calcified organisms. Given the fan-like calcified fronds of the brown alga Padina pavonica, we evaluated the acute (short-term) effects of a sudden pH drop due to a submarine volcanic eruption (October 2011–early March 2012) affecting offshore waters around El Hierro Island (Canary Islands, Spain). We further studied the chronic (long-term) effects of the continuous decrease in pH in the last decades around the Canarian waters. In both the observational and retrospective studies (using herbarium collections of P. pavonica thalli from the overall Canarian Archipelago), the percent of surface calcium carbonate coverage of P. pavonica thalli were contrasted with oceanographic data collected either in situ (volcanic eruption event) or from the ESTOC marine observatory data series (herbarium study). Results showed that this calcified alga is sensitive to acute and chronic environmental pH changes. In both cases, pH changes predicted surface thallus calcification, including a progressive decalcification over the last three decades. This result concurs with previous studies where calcareous organisms decalcify under more acidic conditions. Hence, Padina pavonica can be implemented as a bio-indicator of ocean acidification (at short and long time scales) for monitoring purposes over wide geographic ranges, as this macroalga is affected and thrives (unlike strict calcifiers) under more acidic conditions. PMID:25268231

  19. Effects of ocean acidification on the brown alga Padina pavonica: decalcification due to acute and chronic events.

    PubMed

    Gil-Díaz, Teba; Haroun, Ricardo; Tuya, Fernando; Betancor, Séfora; Viera-Rodríguez, María A

    2014-01-01

    Since the industrial revolution, anthropogenic CO₂ emissions have caused ocean acidification, which particularly affects calcified organisms. Given the fan-like calcified fronds of the brown alga Padina pavonica, we evaluated the acute (short-term) effects of a sudden pH drop due to a submarine volcanic eruption (October 2011-early March 2012) affecting offshore waters around El Hierro Island (Canary Islands, Spain). We further studied the chronic (long-term) effects of the continuous decrease in pH in the last decades around the Canarian waters. In both the observational and retrospective studies (using herbarium collections of P. pavonica thalli from the overall Canarian Archipelago), the percent of surface calcium carbonate coverage of P. pavonica thalli were contrasted with oceanographic data collected either in situ (volcanic eruption event) or from the ESTOC marine observatory data series (herbarium study). Results showed that this calcified alga is sensitive to acute and chronic environmental pH changes. In both cases, pH changes predicted surface thallus calcification, including a progressive decalcification over the last three decades. This result concurs with previous studies where calcareous organisms decalcify under more acidic conditions. Hence, Padina pavonica can be implemented as a bio-indicator of ocean acidification (at short and long time scales) for monitoring purposes over wide geographic ranges, as this macroalga is affected and thrives (unlike strict calcifiers) under more acidic conditions.

  20. Evaluation of the Methods and Management of Acute Coronary Events (EMMACE)-3: protocol for a longitudinal study

    PubMed Central

    Alabas, O A; West, R M; Gillott, R G; Khatib, R; Hall, A S; Gale, C P

    2015-01-01

    Introduction Patients with cardiovascular disease are living longer and are more frequently accessing healthcare resources. The Evaluation of the Methods and Management of Acute Coronary Events (EMMACE)-3 national study is designed to improve understanding of the effect of quality of care on health-related outcomes for patients hospitalised with acute coronary syndrome (ACS). Methods and analysis EMMACE-3 is a longitudinal study of 5556 patients hospitalised with an ACS in England. The study collects repeated measures of health-related quality of life, information about medications and patient adherence profiles, a survey of hospital facilities, and morbidity and mortality data from linkages to multiple electronic health records. Together with EMMACE-3X and EMMACE-4, EMMACE-3 will assimilate detailed information for about 13 000 patients across more than 60 hospitals in England. Ethics and dissemination EMMACE-3 was given a favourable ethical opinion by Leeds (West) Research Ethics committee (REC reference: 10/H131374). On successful application, study data will be shared with academic collaborators. The findings from EMMACE-3 will be disseminated through peer-reviewed publications, at scientific conferences, the media, and through patient and public involvement. Study registration number ClinicalTrials.gov Identifier: NCT01808027. Information about the study is also available at EMMACE.org. PMID:26105029

  1. Acute inhibition of ATP-sensitive K+ channels impairs skeletal muscle vascular control in rats during treadmill exercise

    PubMed Central

    Copp, Steven W.; Ferguson, Scott K.; Sims, Gabrielle E.; Poole, David C.; Musch, Timothy I.

    2015-01-01

    The ATP-sensitive K+ (KATP) channel is part of a class of inward rectifier K+ channels that can link local O2 availability to vasomotor tone across exercise-induced metabolic transients. The present investigation tested the hypothesis that if KATP channels are crucial to exercise hyperemia, then inhibition via glibenclamide (GLI) would lower hindlimb skeletal muscle blood flow (BF) and vascular conductance during treadmill exercise. In 27 adult male Sprague-Dawley rats, mean arterial pressure, blood lactate concentration, and hindlimb muscle BF (radiolabeled microspheres) were determined at rest (n = 6) and during exercise (n = 6–8, 20, 40, and 60 m/min, 5% incline, i.e., ∼60–100% maximal O2 uptake) under control and GLI conditions (5 mg/kg intra-arterial). At rest and during exercise, mean arterial pressure was higher (rest: 17 ± 3%, 20 m/min: 5 ± 1%, 40 m/min: 5 ± 2%, and 60 m/min: 5 ± 1%, P < 0.05) with GLI. Hindlimb muscle BF (20 m/min: 16 ± 7%, 40 m/min: 30 ± 9%, and 60 m/min: 20 ± 8%) and vascular conductance (20 m/min: 20 ± 7%, 40 m/min: 33 ± 8%, and 60 m/min: 24 ± 8%) were lower with GLI during exercise at 20, 40, and 60 m/min, respectively (P < 0.05 for all) but not at rest. Within locomotory muscles, there was a greater fractional reduction present in muscles comprised predominantly of type I and type IIa fibers at all exercise speeds (P < 0.05). Additionally, blood lactate concentration was 106 ± 29% and 44 ± 15% higher during exercise with GLI at 20 and 40 m/min, respectively (P < 0.05). That KATP channel inhibition reduces hindlimb muscle BF during exercise in rats supports the obligatory contribution of KATP channels in large muscle mass exercise-induced hyperemia. PMID:25820394

  2. Acute inhibition of ATP-sensitive K+ channels impairs skeletal muscle vascular control in rats during treadmill exercise.

    PubMed

    Holdsworth, Clark T; Copp, Steven W; Ferguson, Scott K; Sims, Gabrielle E; Poole, David C; Musch, Timothy I

    2015-06-01

    The ATP-sensitive K(+) (KATP) channel is part of a class of inward rectifier K(+) channels that can link local O2 availability to vasomotor tone across exercise-induced metabolic transients. The present investigation tested the hypothesis that if KATP channels are crucial to exercise hyperemia, then inhibition via glibenclamide (GLI) would lower hindlimb skeletal muscle blood flow (BF) and vascular conductance during treadmill exercise. In 27 adult male Sprague-Dawley rats, mean arterial pressure, blood lactate concentration, and hindlimb muscle BF (radiolabeled microspheres) were determined at rest (n = 6) and during exercise (n = 6-8, 20, 40, and 60 m/min, 5% incline, i.e., ~60-100% maximal O2 uptake) under control and GLI conditions (5 mg/kg intra-arterial). At rest and during exercise, mean arterial pressure was higher (rest: 17 ± 3%, 20 m/min: 5 ± 1%, 40 m/min: 5 ± 2%, and 60 m/min: 5 ± 1%, P < 0.05) with GLI. Hindlimb muscle BF (20 m/min: 16 ± 7%, 40 m/min: 30 ± 9%, and 60 m/min: 20 ± 8%) and vascular conductance (20 m/min: 20 ± 7%, 40 m/min: 33 ± 8%, and 60 m/min: 24 ± 8%) were lower with GLI during exercise at 20, 40, and 60 m/min, respectively (P < 0.05 for all) but not at rest. Within locomotory muscles, there was a greater fractional reduction present in muscles comprised predominantly of type I and type IIa fibers at all exercise speeds (P < 0.05). Additionally, blood lactate concentration was 106 ± 29% and 44 ± 15% higher during exercise with GLI at 20 and 40 m/min, respectively (P < 0.05). That KATP channel inhibition reduces hindlimb muscle BF during exercise in rats supports the obligatory contribution of KATP channels in large muscle mass exercise-induced hyperemia. PMID:25820394

  3. Predictive value of CHADS2 score for cardiovascular events in patients with acute coronary syndrome and documented coronary artery disease

    PubMed Central

    Kang, In Sook; Pyun, Wook Bum; Shin, Gil Ja

    2016-01-01

    Background/Aims: The CHADS2 score, used to predict the risk of ischemic stroke in atrial fibrillation (AF) patients, has been reported recently to predict ischemic stroke in patients with coronary heart disease, regardless of the presence of AF. However, little data are available regarding the relationship between the CHADS2 score and cardiovascular outcomes. Methods: This was a retrospective study on 104 patients admitted for acute coronary syndrome (ACS) who underwent coronary angiography, carotid ultrasound, and transthoracic echocardiography. Results: The mean age of the subjects was 60.1 ± 12.6 years. The CHADS2 score was as follows: 0 in 46 patients (44.2%), 1 in 31 (29.8%), 2 in 18 (17.3%), and ≥ 3 in 9 patients (8.7%). The left atrial volume index (LAVi) showed a positive correlation with the CHADS2 score (20.8 ± 5.9 for 0; 23.2 ± 6.7 for 1; 26.6 ± 10.8 for 2; and 30.3 ± 8.3 mL/m2 for ≥3; p = 0.001). The average carotid total plaque area was significantly increased with CHADS2 scores ≥ 2 (4.97 ± 7.17 mm2 vs. 15.52 ± 14.61 mm2; p = 0.002). Eight patients experienced cardiovascular or cerebrovascular (CCV) events during a mean evaluation period of 662 days. A CHADS2 score ≥ 3 was related to an increase in the risk of CCV events (hazard ratio, 14.31; 95% confidence interval, 3.53 to 58.06). Furthermore, LAVi and the severity of coronary artery obstructive disease were also associated with an increased risk of CCV events. Conclusions: The CHADS2 score may be a useful prognostic tool for predicting CCV events in ACS patients with documented coronary artery disease. PMID:26767860

  4. 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. PMID:25140454

  5. 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.

  6. Management of Acute Submacular Hemorrhage with Intravitreal Injection of Tenecteplase, Anti-vascular Endothelial Growth Factor and Gas

    PubMed Central

    Lee, Jung Pil; Park, Jun Sang; Kwon, Oh Woong; You, Yong Sung

    2016-01-01

    Purpose To evaluate the visual and anatomical outcomes for neovascular age-related macular degeneration with submacular hemorrhage after intravitreal injections of tenecteplase (TNK), anti-vascular endothelial growth factor (VEGF) and expansile gas. Methods This study was a retrospective clinical case series following 25 eyes of 25 patients. All patients received a triple injection using 0.05 mL TNK (50 µg), 0.05 mL anti-VEGF and 0.3 mL of perfluoropropane gas. Retreatment with anti-VEGF was performed as needed. Preoperative and postoperative best-corrected visual acuity and central retinal thickness were analyzed. Results The mean logarithm of the minimum angle of resolution of best-corrected visual acuity improved significantly from 1.09 ± 0.77 at baseline to 0.52 ± 0.60 at 12 months (p < 0.001). The mean central retinal thickness also improved significantly from 545 ± 156 at baseline to 266 ± 107 at 12 months (p < 0.001). A visual improvement of 0.3 logarithm of the minimum angle of resolution unit or more was achieved in 15 eyes (60%). During the 12 postoperative months, an average of 4.04 intravitreal anti-VEGF injections was applied. Conclusions A triple injection of TNK, anti-VEGF, and a gas appears to be safe and effective for the treatment of submacular hemorrhage secondary to neovascular age-related macular degeneration. PMID:27247518

  7. One-year Mortality after an Acute Coronary Event and its Clinical Predictors: The ERICO Study

    PubMed Central

    Santos, Itamar Souza; Goulart, Alessandra Carvalho; Brandão, Rodrigo Martins; Santos, Rafael Caire de Oliveira; Bittencourt, Márcio Sommer; Sitnik, Débora; Pereira, Alexandre Costa; Pastore, Carlos Alberto; Samesima, Nelson; Lotufo, Paulo Andrade; Bensenor, Isabela Martins

    2015-01-01

    Background Information about post-acute coronary syndrome (ACS) survival have been mostly short-term findings or based on specialized, cardiology referral centers. Objectives To describe one-year case-fatality rates in the Strategy of Registry of Acute Coronary Syndrome (ERICO) cohort, and to study baseline characteristics as predictors. Methods We analyzed data from 964 ERICO participants enrolled from February 2009 to December 2012. We assessed vital status by telephone contact and official death certificate searches. The cause of death was determined according to the official death certificates. We used log-rank tests to compare the probabilities of survival across subgroups. We built crude and adjusted (for age, sex and ACS subtype) Cox regression models to study if the ACS subtype or baseline characteristics were independent predictors of all-cause or cardiovascular mortality. Results We identified 110 deaths in the cohort (case-fatality rate, 12.0%). Age [Hazard ratio (HR) = 2.04 per 10 year increase; 95% confidence interval (95%CI) = 1.75–2.38], non-ST elevation myocardial infarction (HR = 3.82 ; 95%CI = 2.21–6.60) or ST elevation myocardial infarction (HR = 2.59; 95%CI = 1.38–4.89) diagnoses, and diabetes (HR = 1.78; 95%CI = 1.20‑2.63) were significant risk factors for all-cause mortality in the adjusted models. We found similar results for cardiovascular mortality. A previous coronary artery disease diagnosis was also an independent predictor of all-cause mortality (HR = 1.61; 95%CI = 1.04–2.50), but not for cardiovascular mortality. Conclusion We found an overall one-year mortality rate of 12.0% in a sample of post-ACS patients in a community, non-specialized hospital in São Paulo, Brazil. Age, ACS subtype, and diabetes were independent predictors of poor one‑year survival for overall and cardiovascular-related causes. PMID:25993485

  8. A New Computational Model for Neuro-Glio-Vascular Coupling: Astrocyte Activation Can Explain Cerebral Blood Flow Nonlinear Response to Interictal Events.

    PubMed

    Blanchard, Solenna; Saillet, Sandrine; Ivanov, Anton; Benquet, Pascal; Bénar, Christian-George; Pélégrini-Issac, Mélanie; Benali, Habib; Wendling, Fabrice

    2016-01-01

    Developing a clear understanding of the relationship between cerebral blood flow (CBF) response and neuronal activity is of significant importance because CBF increase is essential to the health of neurons, for instance through oxygen supply. This relationship can be investigated by analyzing multimodal (fMRI, PET, laser Doppler…) recordings. However, the important number of intermediate (non-observable) variables involved in the underlying neurovascular coupling makes the discovery of mechanisms all the more difficult from the sole multimodal data. We present a new computational model developed at the population scale (voxel) with physiologically relevant but simple equations to facilitate the interpretation of regional multimodal recordings. This model links neuronal activity to regional CBF dynamics through neuro-glio-vascular coupling. This coupling involves a population of glial cells called astrocytes via their role in neurotransmitter (glutamate and GABA) recycling and their impact on neighboring vessels. In epilepsy, neuronal networks generate epileptiform discharges, leading to variations in astrocytic and CBF dynamics. In this study, we took advantage of these large variations in neuronal activity magnitude to test the capacity of our model to reproduce experimental data. We compared simulations from our model with isolated epileptiform events, which were obtained in vivo by simultaneous local field potential and laser Doppler recordings in rats after local bicuculline injection. We showed a predominant neuronal contribution for low level discharges and a significant astrocytic contribution for higher level discharges. Besides, neuronal contribution to CBF was linear while astrocytic contribution was nonlinear. Results thus indicate that the relationship between neuronal activity and CBF magnitudes can be nonlinear for isolated events and that this nonlinearity is due to astrocytic activity, highlighting the importance of astrocytes in the

  9. A New Computational Model for Neuro-Glio-Vascular Coupling: Astrocyte Activation Can Explain Cerebral Blood Flow Nonlinear Response to Interictal Events

    PubMed Central

    Blanchard, Solenna; Saillet, Sandrine; Ivanov, Anton; Benquet, Pascal; Bénar, Christian-George; Pélégrini-Issac, Mélanie; Benali, Habib; Wendling, Fabrice

    2016-01-01

    Developing a clear understanding of the relationship between cerebral blood flow (CBF) response and neuronal activity is of significant importance because CBF increase is essential to the health of neurons, for instance through oxygen supply. This relationship can be investigated by analyzing multimodal (fMRI, PET, laser Doppler…) recordings. However, the important number of intermediate (non-observable) variables involved in the underlying neurovascular coupling makes the discovery of mechanisms all the more difficult from the sole multimodal data. We present a new computational model developed at the population scale (voxel) with physiologically relevant but simple equations to facilitate the interpretation of regional multimodal recordings. This model links neuronal activity to regional CBF dynamics through neuro-glio-vascular coupling. This coupling involves a population of glial cells called astrocytes via their role in neurotransmitter (glutamate and GABA) recycling and their impact on neighboring vessels. In epilepsy, neuronal networks generate epileptiform discharges, leading to variations in astrocytic and CBF dynamics. In this study, we took advantage of these large variations in neuronal activity magnitude to test the capacity of our model to reproduce experimental data. We compared simulations from our model with isolated epileptiform events, which were obtained in vivo by simultaneous local field potential and laser Doppler recordings in rats after local bicuculline injection. We showed a predominant neuronal contribution for low level discharges and a significant astrocytic contribution for higher level discharges. Besides, neuronal contribution to CBF was linear while astrocytic contribution was nonlinear. Results thus indicate that the relationship between neuronal activity and CBF magnitudes can be nonlinear for isolated events and that this nonlinearity is due to astrocytic activity, highlighting the importance of astrocytes in the

  10. Use of emergency medical services in the second gulf registry of acute coronary events.

    PubMed

    AlHabib, Khalid F; Alfaleh, Hussam; Hersi, Ahmad; Kashour, Tarek; Alsheikh-Ali, Alawi A; Suwaidi, Jassim Al; Sulaiman, Kadhim; Saif, Shukri Al; Almahmeed, Wael; Asaad, Nidal; Amin, Haitham; Al-Motarreb, Ahmed; Thalib, Lukman

    2014-09-01

    Data are scarce regarding emergency medical service (EMS) usage by patients with acute coronary syndrome (ACS) in the Arabian Gulf region. This 9-month in-hospital prospective ACS registry was conducted in Arabian Gulf countries, with 30-day and 1-year follow-up mortality rates. Of 5184 patients with ACS, 1293 (25%) arrived at the hospital by EMS. The EMS group (vs non-EMS) was more likely to be male, have cardiac arrest on presentation, be current or exsmokers, and have moderate or severe left ventricular dysfunction and ST-segment elevation myocardial infarction (STEMI). The EMS group had higher crude mortality rates during hospitalization and after hospital discharge but not after adjustment for clinical factors and treatments. The EMSs are underused in the Arabian Gulf region. Short- and long-term mortality rates in patients with ACS are similar between those who used and did not use EMS. Quality improvement in the EMS infrastructure and establishment of integrated STEMI networks are urgently needed. PMID:24019088

  11. Early coagulation events induce acute lung injury in a rat model of blunt traumatic brain injury.

    PubMed

    Yasui, Hideki; Donahue, Deborah L; Walsh, Mark; Castellino, Francis J; Ploplis, Victoria A

    2016-07-01

    Acute lung injury (ALI) and systemic coagulopathy are serious complications of traumatic brain injury (TBI) that frequently lead to poor clinical outcomes. Although the release of tissue factor (TF), a potent initiator of the extrinsic pathway of coagulation, from the injured brain is thought to play a key role in coagulopathy after TBI, its function in ALI following TBI remains unclear. In this study, we investigated whether the systemic appearance of TF correlated with the ensuing coagulopathy that follows TBI in ALI using an anesthetized rat blunt trauma TBI model. Blood and lung samples were obtained after TBI. Compared with controls, pulmonary edema and increased pulmonary permeability were observed as early as 5 min after TBI without evidence of norepinephrine involvement. Systemic TF increased at 5 min and then diminished 60 min after TBI. Lung injury and alveolar hemorrhaging were also observed as early as 5 min after TBI. A biphasic elevation of TF was observed in the lungs after TBI, and TF-positive microparticles (MPs) were detected in the alveolar spaces. Fibrin(ogen) deposition was also observed in the lungs within 60 min after TBI. Additionally, preadministration of a direct thrombin inhibitor, Refludan, attenuated lung injuries, thus implicating thrombin as a direct participant in ALI after TBI. The results from this study demonstrated that enhanced systemic TF may be an initiator of coagulation activation that contributes to ALI after TBI. PMID:27190065

  12. Vascular Cures

    MedlinePlus

    ... Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease Chronic Venous Insufficiency Congenital Vascular Malformation Critical Limb Ischemia (CLI) Deep Vein Thrombosis (DVT) Diabetes and Vascular Disease Fibromuscular Dysplasia High ...

  13. Optical coherence tomography based microangiography for quantitative monitoring of structural and vascular changes in a rat model of acute uveitis in vivo: a preliminary study

    NASA Astrophysics Data System (ADS)

    Choi, Woo June; Pepple, Kathryn L.; Zhi, Zhongwei; Wang, Ruikang K.

    2015-01-01

    Uveitis models in rodents are important in the investigation of pathogenesis in human uveitis and the development of appropriate therapeutic strategies for treatment. Quantitative monitoring of ocular inflammation in small animal models provides an objective metric to assess uveitis progression and/or therapeutic effects. We present a new application of optical coherence tomography (OCT) and OCT-based microangiography (OMAG) to a rat model of acute anterior uveitis induced by intravitreal injection of a killed mycobacterial extract. OCT/OMAG is used to provide noninvasive three-dimensional imaging of the anterior segment of the eyes prior to injection (baseline) and two days post-injection (peak inflammation) in rats with and without steroid treatments. OCT imaging identifies characteristic structural and vascular changes in the anterior segment of the inflamed animals when compared to baseline images. Characteristics of inflammation identified include anterior chamber cells, corneal edema, pupillary membranes, and iris vasodilation. In contrast, no significant difference from the control is observed for the steroid-treated eye. These findings are compared with the histology assessment of the same eyes. In addition, quantitative measurements of central corneal thickness and iris vessel diameter are determined. This pilot study demonstrates that OCT-based microangiography promises to be a useful tool for the assessment and management of uveitis in vivo.

  14. Usefulness of Coronary Atheroma Burden to Predict Cardiovascular Events in Patients Presenting With Acute Coronary Syndromes (from the PROSPECT Study).

    PubMed

    Shan, Peiren; Mintz, Gary S; McPherson, John A; De Bruyne, Bernard; Farhat, Naim Z; Marso, Steven P; Serruys, Patrick W; Stone, Gregg W; Maehara, Akiko

    2015-12-01

    We investigated the relation between overall atheroma burden and clinical events in the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study. In PROSPECT, 660 patients (3,229 nonculprit lesions with a plaque burden ≥ 40% and complete intravascular ultrasound data) were divided into tertiles according to baseline percent atheroma volume (PAV: total plaque/vessel volume). Patients were followed for 3.4 years (median); major adverse cardiac events (MACE: death from cardiac causes, cardiac arrest, myocardial infarction, or rehospitalization because of unstable or progressive angina) were adjudicated to either culprit or nonculprit lesions. Compared with patients in low or intermediate PAV tertiles, patients in the high PAV tertile had the greatest prevalence of plaque rupture and radiofrequency thin-cap fibroatheroma (VH-TCFA) and the highest percentage of necrotic core volume; they were also more likely to have high-risk lesion characteristics: ≥ 1 lesion with minimal luminal area ≤ 4 mm(2), plaque burden >70%, and/or VH-TCFA. Three-year cumulative nonculprit lesion-related MACE was greater in the intermediate and high tertiles than in the low tertile (6.3% vs 14.7% vs 15.1%, low vs intermediate vs high tertiles, p = 0.009). On Cox multivariable analysis, insulin-dependent diabetes (hazard ratio [HR] 3.98, p = 0.002), PAV (HR 1.06, p = 0.03), and the presence of ≥1 VH-TCFA (HR 1.80, p = 0.02) were independent predictors of nonculprit MACE. In conclusion, increasing baseline overall atheroma burden was associated with more advanced, complex, and vulnerable intravascular ultrasound lesion morphology and independently predicted nonculprit lesion-related MACE in patients with acute coronary syndromes after successful culprit lesion intervention.

  15. Referrals in Acute Coronary Events for CARdiac Catheterization: The RACE CAR trial

    PubMed Central

    Kreatsoulas, Catherine; Sloane, Debi; Pogue, Janice; Velianou, James L; Anand, Sonia S

    2010-01-01

    BACKGROUND: Women with acute coronary syndromes have lower rates of cardiac catheterization (CC) than men. OBJECTIVE: To determine whether sex/gender, age, risk level and patient preference influence physician decision making to refer patients for CC. METHODS: Twelve clinical scenarios controlling for sex/gender, age (55 or 75 years of age), Thrombolysis in Myocardial Infarction risk score (low, moderate or high) and patient preference for CC (agreeable or refused/no preference expressed) were designed. Scenarios were administered to specialists across Canada using a web-based computerized survey instrument. Questions were standardized using a five-point Likert scale ranging from 1 (very unlikely to benefit from CC) to 5 (very likely to benefit from CC). Outcomes were assessed using a two-tailed mixed linear regression model. RESULTS: Of 237 scenarios, physicians rated men as more likely to benefit from CC than women (mean [± SE] 4.44±0.07 versus 4.25±0.07, P=0.03), adjusted for age, risk and patient preference. Low-risk men were perceived to benefit more than low-risk women (4.20±0.13 versus 3.54±0.14, P<0.01), and low-risk younger patients were perceived to benefit more than low-risk older patients (4.52±0.17 versus 3.22±0.16, P<0.01). Regardless of risk, patients who agreed to CC were perceived as more likely to benefit from CC than patients who were disagreeable or made no comment at all (5.0±0.23, 3.67±0.21, 2.95±0.14, respectively, P<0.01). CONCLUSION: Canadian specialists’ decisions to refer patients for CC appear to be influenced by sex/gender, age and patient preference in clinical scenarios in which cardiac risk is held constant. Future investigation of possible age and sex/gender biases as proxies for risk is warranted. PMID:20931097

  16. Bleeding Risk during Treatment of Acute Thrombotic Events with Subcutaneous LMWH Compared to Intravenous Unfractionated Heparin; A Systematic Review

    PubMed Central

    Costantino, Giorgio; Ceriani, Elisa; Rusconi, Anna Maria; Podda, Gian Marco; Montano, Nicola; Duca, Piergiorgio; Cattaneo, Marco; Casazza, Giovanni

    2012-01-01

    Background Low Molecular Weight Heparins (LMWH) are at least as effective antithrombotic drugs as Unfractionated Heparin (UFH). However, it is still unclear whether the safety profiles of LMWH and UFH differ. We performed a systematic review to compare the bleeding risk of fixed dose subcutaneous LMWH and adjusted dose UFH for treatment of venous thromboembolism (VTE) or acute coronary syndromes (ACS). Major bleeding was the primary end point. Methods Electronic databases (MEDLINE, EMBASE, and the Cochrane Library) were searched up to May 2010 with no language restrictions. Randomized controlled trials in which subcutaneous LMWH were compared to intravenous UFH for the treatment of acute thrombotic events were selected. Two reviewers independently screened studies and extracted data on study design, study quality, incidence of major bleeding, patients’ characteristics, type, dose and number of daily administrations of LMWH, co-treatments, study end points and efficacy outcome. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using the random effects model. Results Twenty-seven studies were included. A total of 14,002 patients received UFH and 14,635 patients LMWH. Overall, no difference in major bleeding was observed between LMWH patients and UFH (OR = 0.79, 95% CI 0.60–1.04). In patients with VTE LMWH appeared safer than UFH, (OR = 0.68, 95% CI 0.47–1.00). Conclusion The results of our systematic review suggest that the use of LMWH in the treatment of VTE might be associated with a reduction in major bleeding compared with UFH. The choice of which heparin to use to minimize bleeding risk must be based on the single patient, taking into account the bleeding profile of different heparins in different settings. PMID:22984525

  17. Acute aerobic exercise enhances attentional modulation of somatosensory event-related potentials during a tactile discrimination task.

    PubMed

    Popovich, Christina; Staines, W Richard

    2015-03-15

    Neuroimaging research has shown that acute bouts of moderate intensity aerobic exercise can enhance attention-based neuronal activity in frontal brain regions, namely in the prefrontal cortex (PFC), as well as improve cognitive performance. The circuitry of the PFC is complex with extensive reciprocal corticocortical and thalamocortical connections, yet it remains unclear if aerobic exercise can also assist attentional control over modality-specific sensory cortices. To test this, we used a tactile discrimination task to compare tactile event-related potentials (ERPs) prior to and following an acute bout of moderate intensity aerobic exercise. We hypothesized that exercise preceding performance of the task would result in more efficient sensory gating of irrelevant/non-attended and enhancement of relevant/attended sensory information, respectively. Participants received vibrotactile stimulation to the second and fifth digit on the left hand and reported target stimuli on one digit only. ERP amplitudes for the P50, P100, N140 and long latency positivity (LLP) were quantified for attended and non-attended trials at FC4, C4, CP4 and P4 while P300 amplitudes were quantified in response to attended target stimuli at electrodes FCZ, CZ and CPZ. Results showed no effect of attention on the P50, however, both P100 and LLP amplitudes were significantly greater during attended, task-relevant trials, while the N140 was enhanced for non-attended, task-irrelevant stimuli. Moreover, unattended N140 amplitudes over parietal sites contralateral to stimulation were significantly greater post-exercise versus pre-exercise, while LLP modulation varied with greater unattended amplitudes post-exercise over frontal sites and greater attended amplitudes post-exercise over parietal sites. These results suggest that a single session of moderate intensity aerobic exercise facilitated the sensory gating of task-irrelevant tactile stimuli so that relevant sensory signals could be enhanced at

  18. Statistical Prediction of Solar Particle Event Frequency Based on the Measurements of Recent Solar Cycles for Acute Radiation Risk Analysis

    NASA Technical Reports Server (NTRS)

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

    2009-01-01

    Large solar particle events (SPEs) present significant acute radiation risks to the crew members during extra-vehicular activities (EVAs) or in lightly shielded space vehicles for space missions beyond the protection of the Earth's magnetic field. Acute radiation sickness (ARS) can impair performance and result in failure of the mission. Improved forecasting capability and/or early-warning systems and proper shielding solutions are required to stay within NASA's short-term dose limits. Exactly how to make use of observations of SPEs for predicting occurrence and size is a great challenge, because SPE occurrences themselves are random in nature even though the expected frequency of SPEs is strongly influenced by the time position within the solar activity cycle. Therefore, we developed a probabilistic model approach, where a cumulative expected occurrence curve of SPEs for a typical solar cycle was formed from a non-homogeneous Poisson process model fitted to a database of proton fluence measurements of SPEs that occurred during the past 5 solar cycles (19 - 23) and those of large SPEs identified from impulsive nitrate enhancements in polar ice. From the fitted model, the expected frequency of SPEs was estimated at any given proton fluence threshold (Phi(sub E)) with energy (E) >30 MeV during a defined space mission period. Corresponding Phi(sub E) (E=30, 60, and 100 MeV) fluence distributions were simulated with a random draw from a gamma distribution, and applied for SPE ARS risk analysis for a specific mission period. It has been found that the accurate prediction of deep-seated organ doses was more precisely predicted at high energies, Phi(sub 100), than at lower energies such as Phi(sub 30) or Phi(sub 60), because of the high penetration depth of high energy protons. Estimates of ARS are then described for 90th and 95th percentile events for several mission lengths and for several likely organ dose-rates. The ability to accurately measure high energy protons

  19. Overexpression of SET is a recurrent event associated with poor outcome and contributes to protein phosphatase 2A inhibition in acute myeloid leukemia

    PubMed Central

    Cristóbal, Ion; Garcia-Orti, Laura; Cirauqui, Cristina; Cortes-Lavaud, Xabier; García-Sánchez, María A.; Calasanz, María J.; Odero, María D.

    2012-01-01

    Background Protein phosphatase 2A is a novel potential therapeutic target in several types of chronic and acute leukemia, and its inhibition is a common event in acute myeloid leukemia. Upregulation of SET is essential to inhibit protein phosphatase 2A in chronic myeloid leukemia, but its importance in acute myeloid leukemia has not yet been explored. Design and Methods We quantified SET expression by real time reverse transcriptase polymerase chain reaction in 214 acute myeloid leukemia patients at diagnosis. Western blot was performed in acute myeloid leukemia cell lines and in 16 patients’ samples. We studied the effect of SET using cell viability assays. Bioinformatics analysis of the SET promoter, chromatin immunoprecipitation, and luciferase assays were performed to evaluate the transcriptional regulation of SET. Results SET overexpression was found in 60/214 patients, for a prevalence of 28%. Patients with SET overexpression had worse overall survival (P<0.01) and event-free survival (P<0.01). Deregulation of SET was confirmed by western blot in both cell lines and patients’ samples. Functional analysis showed that SET promotes proliferation, and restores cell viability after protein phosphatase 2A overexpression. We identified EVI1 overexpression as a mechanism involved in SET deregulation in acute myeloid leukemia cells. Conclusions These findings suggest that SET overexpression is a key mechanism in the inhibition of PP2A in acute myeloid leukemia, and that EVI1 overexpression contributes to the deregulation of SET. Furthermore, SET overexpression is associated with a poor outcome in acute myeloid leukemia, and it can be used to identify a subgroup of patients who could benefit from future treatments based on PP2A activators. PMID:22133779

  20. Effect of Diabetes Mellitus on Frequency of Adverse Events in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention.

    PubMed

    Piccolo, Raffaele; Franzone, Anna; Koskinas, Konstantinos C; Räber, Lorenz; Pilgrim, Thomas; Valgimigli, Marco; Stortecky, Stefan; Rat-Wirtzler, Julie; Silber, Sigmund; Serruys, Patrick W; Jüni, Peter; Heg, Dik; Windecker, Stephan

    2016-08-01

    Few data are available on the timing of adverse events in relation to the status of diabetes mellitus and the type of acute coronary syndrome (ACS). We investigated this issue in diabetic and nondiabetic patients admitted with a diagnosis of non-ST-segment elevation ACS (NSTE-ACS) or ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention. Patient-level data from 6 studies (n = 16,601) were pooled and only patients with ACS are included (n = 9,492). Early (0 to 30 days), late (31 to 365 days), and overall (0 to 365 days) events were analyzed. Diabetes mellitus was present in 1,927 patients (20.3%). At 1 year, all-cause mortality was highest for diabetic patients with STEMI (13.4%), followed by diabetic patients with NSTE-ACS (10.3%), nondiabetic patients with STEMI (6.4%) and nondiabetic patients with NSTE-ACS (4.4%; p <0.001). Among patients with diabetes, there was a significant interaction (p <0.001) for STEMI versus NSTE-ACS in early compared with late mortality, due to an excess of early mortality associated with STEMI (9.3% vs 3.7%; hazard ratio 2.31, 95% CI 1.52 to 3.54, p <0.001). Compared with diabetic NSTE-ACS patients, diabetic patients with STEMI had an increased risk of early stent thrombosis (hazard ratio 2.26, 95% CI 1.48 to 3.44, p <0.001), as well as a significant interaction (p = 0.009) in the risk of target lesion revascularization between the early and late follow-up. The distribution of fatal and nonfatal events according to the type of ACS was not influenced by diabetic status. In conclusion, diabetes in ACS setting confers a worse prognosis with 1-year mortality >10% in both STEMI and NSTE-ACS. Notwithstanding the high absolute rates, the temporal distribution of adverse events related to the type of ACS is similar between diabetic and nondiabetic patients.

  1. Gender differences in pre-event health status of young patients with acute myocardial infarction: A VIRGO study analysis

    PubMed Central

    Dreyer, Rachel P; Smolderen, Kim G; Strait, Kelly M; Beltrame, John F; Lichtman, Judith H; Lorenze, Nancy P; D’Onofrio, Gail; Bueno, Héctor; Krumholz, Harlan M; Spertus, John A

    2015-01-01

    Aims We assessed gender differences in pre-event health status (symptoms, functioning, quality of life) in young patients with acute myocardial infarction (AMI), and whether or not this association persists following sequential adjustment for important covariates. We also evaluated the interaction between gender and prior coronary artery disease (CAD), given that aggressive symptom control is a cornerstone of care in those with known coronary disease. Methods and Results A total of 3,501 AMI patients (2,349 women) aged 18–55 years were enrolled from 103 United States/24 Spanish hospitals (2008–2012). Clinical/health status information was obtained by medical record abstraction and patient interviews. Pre-event health status was measured by generic [Short Form-12 (SF-12), EuroQoL [EQ-5D)] and disease-specific [Seattle angina questionnaire (SAQ)] measures. T-test/chi-square and multivariable linear/logistic regression analysis was utilized, sequentially adjusting for covariates. Women had more co-morbidities and significantly lower generic mean health scores than men [SF-12 physical health =43±12 vs. 46±11 and mental health= 44±13 vs. 48±11]; EQ-5D utility index=0.7±0.2 vs. 0.8±0.2, and visual analog scale=63±22 vs. 67±20, P<0.0001 for all. Their disease-specific health status was also worse, with more angina [SAQ angina frequency=83±22 vs. 87±18], worse physical function [physical limitation=78±27 vs. 87±21] and poorer quality of life [55±25 vs. 60±22, P<0.0001 for all]. In multivariable analysis, the association between female gender and worse generic physical/mental health persisted, as well as worse disease-specific physical limitation and quality of life. The interaction between gender and prior CAD was not significant in any of the health status outcomes. Conclusion Young women have worse pre-event health status as compared with men, regardless of their CAD history. While future studies of gender differences should adjust for baseline health

  2. Effect of Diabetes Mellitus on Frequency of Adverse Events in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention.

    PubMed

    Piccolo, Raffaele; Franzone, Anna; Koskinas, Konstantinos C; Räber, Lorenz; Pilgrim, Thomas; Valgimigli, Marco; Stortecky, Stefan; Rat-Wirtzler, Julie; Silber, Sigmund; Serruys, Patrick W; Jüni, Peter; Heg, Dik; Windecker, Stephan

    2016-08-01

    Few data are available on the timing of adverse events in relation to the status of diabetes mellitus and the type of acute coronary syndrome (ACS). We investigated this issue in diabetic and nondiabetic patients admitted with a diagnosis of non-ST-segment elevation ACS (NSTE-ACS) or ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention. Patient-level data from 6 studies (n = 16,601) were pooled and only patients with ACS are included (n = 9,492). Early (0 to 30 days), late (31 to 365 days), and overall (0 to 365 days) events were analyzed. Diabetes mellitus was present in 1,927 patients (20.3%). At 1 year, all-cause mortality was highest for diabetic patients with STEMI (13.4%), followed by diabetic patients with NSTE-ACS (10.3%), nondiabetic patients with STEMI (6.4%) and nondiabetic patients with NSTE-ACS (4.4%; p <0.001). Among patients with diabetes, there was a significant interaction (p <0.001) for STEMI versus NSTE-ACS in early compared with late mortality, due to an excess of early mortality associated with STEMI (9.3% vs 3.7%; hazard ratio 2.31, 95% CI 1.52 to 3.54, p <0.001). Compared with diabetic NSTE-ACS patients, diabetic patients with STEMI had an increased risk of early stent thrombosis (hazard ratio 2.26, 95% CI 1.48 to 3.44, p <0.001), as well as a significant interaction (p = 0.009) in the risk of target lesion revascularization between the early and late follow-up. The distribution of fatal and nonfatal events according to the type of ACS was not influenced by diabetic status. In conclusion, diabetes in ACS setting confers a worse prognosis with 1-year mortality >10% in both STEMI and NSTE-ACS. Notwithstanding the high absolute rates, the temporal distribution of adverse events related to the type of ACS is similar between diabetic and nondiabetic patients. PMID:27289296

  3. [Vascular parkinsonism].

    PubMed

    Marxreiter, F; Winkler, J

    2016-07-01

    Parkinsonism may result from cerebral vascular disorders that feature white matter lesions and small vessel pathology. Vascular Parkinsonism typically presents as lower body Parkinsonism with predominant gait impairment. Urinary incontinence and cognitive decline are additional features of the disease. There is a considerable overlap between vascular Parkinsonism and vascular dementia. We review the clinical characteristics of vascular Parkinsonism and discuss the current treatment approaches, as well as the role of brain imaging for the diagnostic workup. . PMID:27299942

  4. A Rare Occurrence of Simultaneous Venous and Arterial Thromboembolic Events – Lower Limb Deep Venous Thrombosis and Pulmonary Thromboembolism as Initial Presentation in Acute Promyelocytic Leukemia

    PubMed Central

    Kutiyal, Aditya S.; Dharmshaktu, Pramila; Kataria, Babita; Garg, Abhilasha

    2016-01-01

    The development of acute myeloid leukemia has been attributed to various factors, including hereditary, radiation, drugs, and certain occupational exposures. The association between malignancy and venous thromboembolism events is well established. Here, we present a case of a 70-year-old Indian man who had presented with arterial and venous thrombosis, and the patient was later diagnosed with acute promyelocytic leukemia (APL). In our case, the patient presented with right lower limb deep venous thrombosis and pulmonary thromboembolism four months prior to the diagnosis of APL. Although thromboembolic event subsequent to the diagnosis of malignancy, and especially during the chemotherapy has been widely reported, this prior presentation with simultaneous occurrence of both venous and arterial thromboembolism has rarely been reported. We take this opportunity to state the significance of a complete medical evaluation in cases of recurrent or unusual thrombotic events. PMID:26949347

  5. Vascular disease.

    PubMed

    Amlie-Lefond, Catherine; Shaw, Dennis

    2016-01-01

    The child presenting with possible sentinel transient ischemic event or stroke requires prompt diagnosis so that strategies to limit injury and prevent recurrent stroke can be instituted. Cerebral arteriopathy is a potent risk factor for arterial ischemic stroke in childhood. Though acute imaging study in the setting of possible stroke is often a head computed tomography, when possible magnetic resonance imaging (MRI) is recommended as the first-line study as confirmation and imaging evaluation of ischemic stroke will typically require MRI. The MRI scanning approach should include diffusion-weighted imaging (DWI) early in the sequence order, since normal DWI excludes acute infarct with rare exception. In most cases, arterial imaging with time-of-flight (TOF) magnetic resonance angiography (MRA) is warranted. Dedicated MRA may not be possible in the acute setting, but should be pursued as promptly as possible, particularly in the child with findings and history suggestive of arteriopathy, given the high risk of recurrent stroke in these children. MRA can overestimate the degree of arterial compromise due to complex/turbulent flow, and be insensitive to subtle vessel irregularity due to resolution and complex flow. In cases with high imaging suspicion for dissection despite normal MRA findings, catheter angiogram is indicated. A thoughtful, stepwise approach to arterial neuroimaging is critical to optimize diagnosis, treatment, and primary and secondary prevention of childhood stroke. PMID:27430463

  6. Acute effects of ingestion of a novel whey-derived extract on vascular endothelial function in overweight, middle-aged men and women.

    PubMed

    Ballard, Kevin D; Kupchak, Brian R; Volk, Brittanie M; Mah, Eunice; Shkreta, Aida; Liptak, Cary; Ptolemy, Adam S; Kellogg, Mark S; Bruno, Richard S; Seip, Richard L; Maresh, Carl M; Kraemer, William J; Volek, Jeff S

    2013-03-14

    Whey protein intake reduces CVD risk, but little is known whether whey-derived bioactive peptides regulate vascular endothelial function (VEF). We determined the impact of a whey-derived extract (NOP-47) on VEF in individuals with an increased cardiovascular risk profile. Men and women with impaired brachial artery flow-mediated dilation (FMD) (n 21, age 55 (sem 1·3) years, BMI 27·8 (sem 0·6) kg/m2, FMD 3·7 (sem 0·4) %) completed a randomised, cross-over study to examine whether ingestion of NOP-47 (5 g) improves postprandial VEF. Brachial artery FMD, plasma amino acids, insulin, and endothelium-derived vasodilators and vasoconstrictors were measured for 2 h after ingestion of NOP-47 or placebo. Acute NOP-47 ingestion increased FMD at 30 min (4·6 (sem 0·5) %) and 120 min (5·1 (sem 0·5) %) post-ingestion (P< 0·05, time × trial interaction), and FMD responses at 120 min were significantly greater in the NOP-47 trial compared with placebo (4·3 (sem 0·5) %). Plasma amino acids increased at 30 min following NOP-47 ingestion (P< 0·05). Serum insulin increased at 15, 30 and 60 min (P< 0·001) following NOP-47 ingestion. No changes were observed between the trials for plasma NO∙ and prostacyclin metabolites or endothelin-1. Ingestion of a rapidly absorbed extract derived from whey protein improved endothelium-dependent dilation in older adults by a mechanism independent of changes in circulating vasoactive compounds. Future investigation is warranted in individuals at an increased CVD risk to further elucidate potential health benefits and the underlying mechanisms of extracts derived from whey. PMID:22691263

  7. Acute effects of ingestion of a novel whey-derived extract on vascular endothelial function in overweight, middle-aged men and women.

    PubMed

    Ballard, Kevin D; Kupchak, Brian R; Volk, Brittanie M; Mah, Eunice; Shkreta, Aida; Liptak, Cary; Ptolemy, Adam S; Kellogg, Mark S; Bruno, Richard S; Seip, Richard L; Maresh, Carl M; Kraemer, William J; Volek, Jeff S

    2013-03-14

    Whey protein intake reduces CVD risk, but little is known whether whey-derived bioactive peptides regulate vascular endothelial function (VEF). We determined the impact of a whey-derived extract (NOP-47) on VEF in individuals with an increased cardiovascular risk profile. Men and women with impaired brachial artery flow-mediated dilation (FMD) (n 21, age 55 (sem 1·3) years, BMI 27·8 (sem 0·6) kg/m2, FMD 3·7 (sem 0·4) %) completed a randomised, cross-over study to examine whether ingestion of NOP-47 (5 g) improves postprandial VEF. Brachial artery FMD, plasma amino acids, insulin, and endothelium-derived vasodilators and vasoconstrictors were measured for 2 h after ingestion of NOP-47 or placebo. Acute NOP-47 ingestion increased FMD at 30 min (4·6 (sem 0·5) %) and 120 min (5·1 (sem 0·5) %) post-ingestion (P< 0·05, time × trial interaction), and FMD responses at 120 min were significantly greater in the NOP-47 trial compared with placebo (4·3 (sem 0·5) %). Plasma amino acids increased at 30 min following NOP-47 ingestion (P< 0·05). Serum insulin increased at 15, 30 and 60 min (P< 0·001) following NOP-47 ingestion. No changes were observed between the trials for plasma NO∙ and prostacyclin metabolites or endothelin-1. Ingestion of a rapidly absorbed extract derived from whey protein improved endothelium-dependent dilation in older adults by a mechanism independent of changes in circulating vasoactive compounds. Future investigation is warranted in individuals at an increased CVD risk to further elucidate potential health benefits and the underlying mechanisms of extracts derived from whey.

  8. Acute stroke after intravitreal bevacizumab to treat choroidal neovascularization due to angioid streaks in pseudoxanthoma elasticum : a severe systemic adverse event after an off-label procedure.

    PubMed

    Besozzi, Gianluca; Ferrara, Andrea; Epifani, Enrico; Intini, Daniela; Apruzzese, Margherita; Provenzano, Antonio; Vetrugno, Michele

    2013-04-01

    To report the occurrence of acute stroke after intravitreal bevacizumab administration to treat choroidal neovascularization due to angioid streaks in a patient affected by pseudoxanthoma elasticum. A 54-year-old man with pseudoxanthoma elasticum had vision loss because of choroidal neovascularization due to angioid streaks. He underwent two intravitreal bevacizumab injections. Three days after the second procedure the patient was afflicted by acute stroke. Intravitreal injection of bevacizumab to treat choroidal neovascularization due to angioid streaks in pseudoxanthoma elasticum could lead to severe systemic adverse events. PMID:23065017

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

    PubMed Central

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

    2016-01-01

    Objectives 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. Design Retrospective cohort study. Setting Finnish healthcare registers. Participants Women aged 45–64 years initiating statin use for primary prevention of cardiovascular disease in 2001–2004 (n=42 807). Outcomes 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. Results 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). Conclusions 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

  10. 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 ...

  11. Influence of gender on the risk of death and adverse events in patients with acute myocardial infarction undergoing pharmacoinvasive strategy.

    PubMed

    Lanaro, Eduardo; Caixeta, Adriano; Soares, Juliana A; Alves, Cláudia Maria Rodrigues; Barbosa, Adriano Henrique Pereira; Souza, José Augusto Marcondes; Sousa, José Marconi Almeida; Amaral, Amaury; Ferreira, Guilherme M; Moreno, Antônio Célio; Júnior, Iran Gonçalves; Stefanini, Edson; Carvalho, Antônio Carlos

    2014-11-01

    Pharmacoinvasive treatment is an acceptable alternative for patients with ST-segment elevation myocardial infarction (STEMI) in developing countries. The present study evaluated the influence of gender on the risks of death and major adverse cardiovascular events (MACE) in this population. Seven municipal emergency rooms and the Emergency Mobile Healthcare Service in São Paulo treated STEMI patients with tenecteplase. The patients were subsequently transferred to a tertiary teaching hospital for early (<24 h) coronary angiography. A total of 469 patients were evaluated [329 men (70.1%)]. Compared to men, women had more advanced age (60.2 ± 12.3 vs. 56.5 ± 11 years; p = 0.002); lower body mass index (BMI; 25.85 ± 5.07 vs. 27.04 ± 4.26 kg/m2; p = 0.009); higher rates of hypertension (70.7 vs. 59.3%, p = 0.02); higher incidence of hypothyroidism (20.0 vs. 5.5%; p < 0.001), chronic renal failure (10.0 vs. 8.8%; p = 0.68), peripheral vascular disease (PVD; 19.3 vs. 4.3%; p = 0.03), and previous history of stroke (6.4 vs. 1.3%; p = 0.13); and higher thrombolysis in myocardial infarction risk scores (40.0 vs. 23.7%; p < 0.001). The overall in-hospital mortality and MACE rates for women versus men were 9.3 versus 4.9% (p = 0.07) and 12.9 versus 7.9% (p = 0.09), respectively. By multivariate analysis, diabetes (OR 4.15; 95% CI 1.86-9.25; p = 0.001), previous stroke (OR 4.81; 95% CI 1.49-15.52; p = 0.009), and hypothyroidism (OR 3.75; 95% CI 1.44-9.81; p = 0.007), were independent predictors of mortality, whereas diabetes (OR 2.05; 95% CI 1.03-4.06; p = 0.04), PVD (OR 2.38; 95% CI 0.88-6.43; p = 0.08), were predictors of MACE. In STEMI patients undergoing pharmacoinvasive strategy, mortality and MACE rates were twice as high in women; however, this was due to a higher prevalence of risk factors and not gender itself. PMID:24671733

  12. Utility of a Genetic Risk Score to Predict Recurrent Cardiovascular Events 1 Year After an Acute Coronary Syndrome: A Pooled Analysis of the RISCA, PRAXY, and TRIUMPH Cohorts

    PubMed Central

    Labos, Christopher; Martinez, Sara C.; Leo Wang, Rui Hao; Lenzini, Petra A.; Pilote, Louise; Bogaty, Peter; Brophy, James M.; Engert, James C.; Cresci, Sharon; Thanassoulis, George

    2015-01-01

    Background Limited evidence exists regarding the utility of genetic risk scores (GRS) in predicting recurrent cardiovascular events after acute coronary syndrome (ACS). We sought to determine whether a GRS would predict early recurrent cardiovascular events within 1 year of ACS. Methods & Results Participants admitted with acute coronary syndromes from the RISCA, PRAXY, and TRIUMPH cohorts, were genotyped for 30 single nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD) or myocardial infarction (MI) in prior genome wide association studies. A 30 SNP CAD/MI GRS was constructed. The primary endpoint was defined as all-cause mortality, recurrent ACS or cardiac re-hospitalization within 1 year of ACS admission. Results across all cohorts for the 30 SNP CAD/MI GRS were pooled using a random-effects model. There were 1040 patients from the RISCA cohort, 691 patients from the PRAXY cohort, and 1772 patients from the TRIUMPH cohort included in the analysis and 389 occurrences of the primary endpoint of recurrent events at 1-year post-ACS. In unadjusted and fully adjusted analyses, a 30 SNP GRS was not significantly associated with recurrent events (HR per allele 0.97 (95%CI 0.91–1.03) for RISCA, HR 0.99 (95%CI 0.93–1.05) for PRAXY, 0.98 (95%CI 0.94–1.02) for TRIUMPH, and 0.98 (95%CI 0.95–1.01) for the pooled analysis). Addition of this GRS to the GRACE risk model did not significantly improve risk prediction. Conclusion The 30 MI SNP GRS was not associated with recurrent events 1-year post ACS in pooled analyses across cohorts and did not improve risk discrimination or reclassification indices. Our results suggest that the genetic etiology of early events post-ACS may differ from later events. PMID:26232166

  13. Impact of acute water and feed deprivation events on growth performance, intestinal characteristics, and serum stress markers in weaned pigs.

    PubMed

    Horn, N; Ruch, F; Miller, G; Ajuwon, K M; Adeola, O

    2014-10-01

    The impact of acute stressors (24-h feed or water deprivation) on growth performance, intestinal characteristics, and serum stress markers in weaned pigs was evaluated. Pigs (6.21 ± 0.29 kg) were allotted in a randomized complete block design to 4 treatments on the basis of BW at the time of weaning. There were 8 mixed-sex pigs in each of 12 pens per treatment. Treatments were arranged as a 2 × 2 factorial and consisted of a feed or water stressor that included a 0- or 24-h deprivation period postweaning, and pigs were subsequently allowed access to feed and water. Growth performance was measured 1, 7, 14, and 28 d postweaning. Serum and intestinal samples were taken 1 and 7 d postweaning. Serum was analyzed for cortisol and corticotrophin-releasing factor, and villus height, crypt depth, and mast cell density were measured in the jejunum and the ileum. Expression of mucin (MUC2), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), claudin 1 (CL-1), occludin (OC), and zonula occludens 1 (ZO-1) genes were measured on d 1 and 7 postweaning in the jejunum and ileum by real-time PCR. There was a decrease (P < 0.05) in ADG with the water stressor 1 d postweaning, although subsequently, there were improvements (P < 0.05) in ADG and feed efficiency. Furthermore, the water stressor reduced ADFI during the last 14 d of the trial and cumulatively (P < 0.05). Seven days postweaning there was an increase (P < 0.05) in jejunal villous height to depth ratio due to the feed stressor and a decrease (P < 0.05) in the ileal villous height to depth ratio due to the water stressor. There was an increase (P < 0.05) in serum cortisol levels due to the water stressor both 1 and 7 d postweaning. Furthermore, there was an increase in serum corticotrophin-releasing factor 1 d but not 7 d postweaning due to the water stressor (P < 0.05). The feed stressor reduced (P < 0.05) TNF-α gene expression, and the water stressor reduced (P < 0.05) OC gene expression in the jejunum 1 d

  14. [Good practice in occupational health services--Certification of stroke as an accident at work. Need for secondary prevention in people returning to work after acute cerebrovascular events].

    PubMed

    Marcinkiewicz, Andrzej; Walusiak-Skorupa, Jolanta

    2015-01-01

    The classification of an acute vascular episode, both heart infarct and stroke, as an accident at work poses difficulties not only for post accidental teams, but also to occupational health professionals, experts and judges at labor and social insurance courts. This article presents the case of a 41-year-old office worker, whose job involved client services. While attending a very aggressive customer she developed solid stress that resulted in symptoms of the central nervous system (headache, speech disturbances). During her hospitalisation at the neurological unit ischemic stroke with transient mixed type aphasia was diagnosed. Magnetic resonance imaging (MRI) scan of the head revealed subacute ischemia. After an analysis of the accident circumstances, the employer's post accidental team decided that ischemic stroke had been an accident at work, because it was a sudden incident due to an external cause inducing work-related traumatic stroke. As a primary cause tough stress and emotional strain due to the situation developed while attending the customer were acknowledged. During control medical check up after 5 months the patient was found to be fit for work, so she could return to work. However, it should be noted that such a check up examination of subjects returning to work after stroke must be holistic, including the evaluation of job predispositions and health education aimed at secondary prevention of heart and vascular diseases with special reference to their risk factors. PMID:26536976

  15. [Good practice in occupational health services--Certification of stroke as an accident at work. Need for secondary prevention in people returning to work after acute cerebrovascular events].

    PubMed

    Marcinkiewicz, Andrzej; Walusiak-Skorupa, Jolanta

    2015-01-01

    The classification of an acute vascular episode, both heart infarct and stroke, as an accident at work poses difficulties not only for post accidental teams, but also to occupational health professionals, experts and judges at labor and social insurance courts. This article presents the case of a 41-year-old office worker, whose job involved client services. While attending a very aggressive customer she developed solid stress that resulted in symptoms of the central nervous system (headache, speech disturbances). During her hospitalisation at the neurological unit ischemic stroke with transient mixed type aphasia was diagnosed. Magnetic resonance imaging (MRI) scan of the head revealed subacute ischemia. After an analysis of the accident circumstances, the employer's post accidental team decided that ischemic stroke had been an accident at work, because it was a sudden incident due to an external cause inducing work-related traumatic stroke. As a primary cause tough stress and emotional strain due to the situation developed while attending the customer were acknowledged. During control medical check up after 5 months the patient was found to be fit for work, so she could return to work. However, it should be noted that such a check up examination of subjects returning to work after stroke must be holistic, including the evaluation of job predispositions and health education aimed at secondary prevention of heart and vascular diseases with special reference to their risk factors.

  16. Current topics on vascular access for hemodialysis.

    PubMed

    Tordoir, J H M; Van Der Sande, F M; De Haan, M W

    2004-09-01

    Vascular access remains the lifeline for end-stage renal failure patients, which have been treated by chronic intermittent hemodialysis. Due to the steady increase in the number of patients with difficulties to create access, in particular in elderly with various comorbidities, the need for more insight and regulations have evolved into the publications of the American and European guidelines. From the latter it may be obvious that an adequate preoperative assessment followed by the creation of autogenous arteriovenous fistulas (AVFs) is far better and preferred to the implantation of grafts. Vascular access maintenance by monitoring and elective percutanuous or surgical revision is of utmost importance to keep the access site functional. Despite up-to-date measures for vascular access maintenance, various complications may treaten not only the access site but also quality and expectance of life. Thrombotic occlusion remains a major event, leading to permanent failure in 10% of AVFs and 20% of grafts each year. Interventional (percutaneous transluminal angioplasty and/or stent implantation) or surgical revision of thrombosed accesses have similar outcomes with a high rate of reinterventions. The elderly diabetic population with peripheral arteriosclerotic obstructive disease is in particular prone to angio-access induced handischemia. When not timely and properly treated this may lead to minor or major amputation, further hampering quality of life. Also, the enormous application in the past 2 decades of acute central venous lines has lead to a significant increase of central venous obstruction with concomittent morbidity and problems creating vascular access in the upper extremities. Radiological intervention in these cases is a primary option, leaving surgical reconstruction as a second best method. It may be obvious that creation and maintenance of hemodialysis vascular access has become an important and time-consuming speciality. Only an up

  17. 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

  18. Increased lung vascular permeability after pancreatitis and trypsin infusion.

    PubMed Central

    Tahamont, M. V.; Barie, P. S.; Blumenstock, F. A.; Hussain, M. H.; Malik, A. B.

    1982-01-01

    We examined the role of proteases in mediating lung vascular injury after acute hemorrhagic pancreatitis. Studies were made in sheep in which pulmonary lymph was collected for assessment of the changes in transvascular fluid and protein exchange. The induction of pancreatitis by injection of trypsin and sodium taurocholate into the pancreas resulted in increases in pulmonary lymph flow and transvascular protein clearance (lymph flow x lymph-to-plasma protein concentration ratio). The pulmonary vascular pressures did not change significantly after pancreatitis, indicating that the increases in pulmonary lymph flow and protein clearance were due to increased pulmonary endothelial permeability. The response to pancreatitis was also characterized by decreases in concentrations of fibrinogen, platelets, and granulocytes. Pulmonary leukostasis was a common morphologic feature in this group. In another group, an intravenous infusion of trypsin, which produced decreases in antiprotease activity comparable to those observed after pancreatitis, also resulted in increases in pulmonary lymph flow and transvascular protein clearance. These increases in lymph fluxes were comparable to those observed after pancreatitis and were also associated with decreases in concentrations of fibrinogen, platelets, and granulocytes. Pulmonary leukostasis was evident in this group upon histologic examination. In a third group, pretreatment with Trasylol prevented the increases in pulmonary lymph flow and transvascular protein clearance after pancreatitis, suggesting that the pancreatitis-induced pulmonary vascular injury is the result of the release of proteases. The results indicate a common pulmonary vascular response to acute pancreatitis and trypsin infusion. The release of proteases into the circulation after acute pancreatitis may be the initiating event mediating the pulmonary vascular injury. Images Figure 7 Figure 8 Figure 9 Figure 10 Figures 11 and 12 PMID:6181692

  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. 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

  1. 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.

  2. 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.

  3. Geospatial relationships of air pollution and acute asthma events across the Detroit–Windsor international border: Study design and preliminary results

    PubMed Central

    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

    2014-01-01

    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. PMID:24220215

  4. Changes of soluble CD40 ligand in the progression of acute myocardial infarction associate to endothelial nitric oxide synthase polymorphisms and vascular endothelial growth factor but not to platelet CD62P expression.

    PubMed

    Napoleão, Patrícia; Monteiro, Maria do Céu; Cabral, Luís B P; Criado, Maria Begoña; Ramos, Catarina; Selas, Mafalda; Viegas-Crespo, Ana Maria; Saldanha, Carlota; Carmo, Miguel Mota; Ferreira, Rui Cruz; Pinheiro, Teresa

    2015-12-01

    Reported in vitro data implicated soluble CD40 ligand (sCD40L) in endothelial dysfunction and angiogenesis. However, whether sCD40L could exert that influence in endothelial dysfunction and angiogenesis after injury in acute myocardial infarction (AMI) patients remains unclear. In the present study, we evaluated the association of sCD40L with markers of platelet activation, endothelial, and vascular function during a recovery period early after AMI. To achieve this goal, the time changes of soluble, platelet-bound, and microparticle-bound CD40L levels over 1 month were assessed in AMI patients and correlated with endothelial nitric oxide synthase (eNOS) polymorphisms, vascular endothelial growth factor (VEGF) concentrations, and platelet expression of P-selectin (CD62P). The association of soluble form, platelet-bound, and microparticle-bound CD40L with CD62P expression on platelets, a marker of platelet activation, was also assessed to evaluate the role of CD40L in the thrombosis, whereas the association with eNOS and VEGF was to evaluate the role of CD40L in vascular dysfunction. This work shows for the first time that time changes of sCD40L over 1 month after myocardial infarct onset were associated with G894T eNOS polymorphism and with the VEGF concentrations, but not to the platelet CD62P expression. These results indicate that, in terms of AMI pathophysiology, the sCD40L cannot be consider just as being involved in thrombosis and inflammation but also as having a relevant role in vascular and endothelial dysfunction. PMID:26279254

  5. Functional COMT Val158Met Polymorphism, Risk of Acute Coronary Events and Serum Homocysteine: The Kuopio Ischaemic Heart Disease Risk Factor Study

    PubMed Central

    Voutilainen, Sari; Tuomainen, Tomi-Pekka; Korhonen, Maarit; Mursu, Jaakko; Virtanen, Jyrki K.; Happonen, Pertti; Alfthan, Georg; Erlund, Iris; North, Kari E.; Mosher, M.J.; Kauhanen, Jussi; Tiihonen, Jari; Kaplan, George A.; Salonen, Jukka T.

    2007-01-01

    Background The role of circulating levels of total homocysteine tHcy in the development of coronary heart disease (CHD) is still under debate. One reason for conflicting results between previous studies on homocysteine and heart diseases could be consequence of different interactions between homocysteine and genes in different study populations. Many genetic factors play a role in folate-homocysteine metabolism, like functional polymorphism (Val108Met) in the Catechol-O-methyltransferase (COMT) gene. Methodology and Findings Our aim was to examine the role of COMT Val158Met polymorphism and interaction of this polymorphism with serum tHcy and folate concentration on the risk of acute coronary and events in middle-aged men from eastern Finland. A population-based prospective cohort of 792 men aged 46–64 years was examined as part of the Kuopio Ischaemic Heart Disease Risk Factor Study. During an average follow-up of 9.3 years, there were 69 acute coronary events in men with no previous history of CHD. When comparing the COMT low activity genotype with the others, we found an age and examination year adjusted hazard rate ratio (HRR) of 1.73 (95% confidence interval (CI), 1.07–2.79), and an age, examination year, serum LDL and HDL cholesterol, and triglyceride concentration, systolic blood pressure and smoking adjusted HRR of 1.77 (95% CI, 1.05–2.77). Although serum tHcy concentration was not statistically significantly associated with acute coronary events (HRR for the highest third versus others 1.52, 95% CI, 0.93–2.49), subjects with both high serum tHcy and the COMT low activity genotype had an additionally increased adjusted risk of HRR 2.94 (95% CI 1.50–5.76) as compared with other men. Conclusions This prospective cohort study suggests that the functional COMT Val158Met polymorphism is associated with increased risk of acute coronary events and it may interact with high serum tHcy levels. PMID:17264883

  6. 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. PMID:27566811

  7. Vascular Diseases

    MedlinePlus

    ... heart and blood vessels, such as diabetes or high cholesterol Smoking Obesity Losing weight, eating healthy foods, being active and not smoking can help vascular disease. Other treatments include medicines and surgery.

  8. High levels of the adhesion molecule CD44 on leukemic cells generate acute myeloid leukemia relapse after withdrawal of the initial transforming event.

    PubMed

    Quéré, R; Andradottir, S; Brun, A C M; Zubarev, R A; Karlsson, G; Olsson, K; Magnusson, M; Cammenga, J; Karlsson, S

    2011-03-01

    Multiple genetic hits are detected in patients with acute myeloid leukemia (AML). To investigate this further, we developed a tetracycline-inducible mouse model of AML, in which the initial transforming event, overexpression of HOXA10, can be eliminated. Continuous overexpression of HOXA10 is required to generate AML in primary recipient mice, but is not essential for maintenance of the leukemia. Transplantation of AML to secondary recipients showed that in established leukemias, ∼80% of the leukemia-initiating cells (LICs) in bone marrow stopped proliferating upon withdrawal of HOXA10 overexpression. However, the population of LICs in primary recipients is heterogeneous, as ∼20% of the LICs induce leukemia in secondary recipients despite elimination of HOXA10-induced overexpression. Intrinsic genetic activation of several proto-oncogenes was observed in leukemic cells resistant to inactivation of the initial transformation event. Interestingly, high levels of the adhesion molecule CD44 on leukemic cells are essential to generate leukemia after removal of the primary event. This suggests that extrinsic niche-dependent factors are also involved in the host-dependent outgrowth of leukemias after withdrawal of HOXA10 overexpression event that initiates the leukemia.

  9. Acute incident rapid response at a mass-gathering event through comprehensive planning systems: a case report from the 2013 Shamrock Shuffle.

    PubMed

    Başdere, Mehmet; Ross, Colleen; Chan, Jennifer L; Mehrotra, Sanjay; Smilowitz, Karen; Chiampas, George

    2014-06-01

    Planning and execution of mass-gathering events involves various challenges. In this case report, the Chicago Model (CM), which was designed to organize and operate such events and to maintain the health and wellbeing of both runners and the public in a more effective way, is described. The Chicago Model also was designed to prepare for unexpected incidents, including disasters, during the marathon event. The model has been used successfully in the planning and execution stages of the Bank of America Shamrock Shuffle and the Bank of America Chicago Marathon since 2008. The key components of the CM are organizational structure, information systems, and communication. This case report describes how the organizers at the 2013 Shamrock Shuffle used the key components of the CM approach in order to respond to an acute incident caused by a man who was threatening to jump off the State Street Bridge. The course route was changed to accommodate this unexpected event, while maintaining access to key health care facilities. The lessons learned from the incident are presented and further improvements to the existing model are proposed. PMID:24820906

  10. A model for emergency department end-of-life communications after acute devastating events--part I: decision-making capacity, surrogates, and advance directives.

    PubMed

    Limehouse, Walter E; Feeser, V Ramana; Bookman, Kelly J; Derse, Arthur

    2012-09-01

    Making decisions for a patient affected by sudden devastating illness or injury traumatizes a patient's family and loved ones. Even in the absence of an emergency, surrogates making end-of-life treatment decisions may experience negative emotional effects. Helping surrogates with these end-of-life decisions under emergent conditions requires the emergency physician (EP) to be clear, making medical recommendations with sensitivity. This model for emergency department (ED) end-of-life communications after acute devastating events comprises the following steps: 1) determine the patient's decision-making capacity; 2) identify the legal surrogate; 3) elicit patient values as expressed in completed advance directives; 4) determine patient/surrogate understanding of the life-limiting event and expectant treatment goals; 5) convey physician understanding of the event, including prognosis, treatment options, and recommendation; 6) share decisions regarding withdrawing or withholding of resuscitative efforts, using available resources and considering options for organ donation; and 7) revise treatment goals as needed. Emergency physicians should break bad news compassionately, yet sufficiently, so that surrogate and family understand both the gravity of the situation and the lack of long-term benefit of continued life-sustaining interventions. EPs should also help the surrogate and family understand that palliative care addresses comfort needs of the patient including adequate treatment for pain, dyspnea, or anxiety. Part I of this communications model reviews determination of decision-making capacity, surrogacy laws, and advance directives, including legal definitions and application of these steps; Part II (which will appear in a future issue of AEM) covers communication moving from resuscitative to end-of-life and palliative treatment. EPs should recognize acute devastating illness or injuries, when appropriate, as opportunities to initiate end-of-life discussions and to

  11. A model for emergency department end-of-life communications after acute devastating events--part I: decision-making capacity, surrogates, and advance directives.

    PubMed

    Limehouse, Walter E; Feeser, V Ramana; Bookman, Kelly J; Derse, Arthur

    2012-09-01

    Making decisions for a patient affected by sudden devastating illness or injury traumatizes a patient's family and loved ones. Even in the absence of an emergency, surrogates making end-of-life treatment decisions may experience negative emotional effects. Helping surrogates with these end-of-life decisions under emergent conditions requires the emergency physician (EP) to be clear, making medical recommendations with sensitivity. This model for emergency department (ED) end-of-life communications after acute devastating events comprises the following steps: 1) determine the patient's decision-making capacity; 2) identify the legal surrogate; 3) elicit patient values as expressed in completed advance directives; 4) determine patient/surrogate understanding of the life-limiting event and expectant treatment goals; 5) convey physician understanding of the event, including prognosis, treatment options, and recommendation; 6) share decisions regarding withdrawing or withholding of resuscitative efforts, using available resources and considering options for organ donation; and 7) revise treatment goals as needed. Emergency physicians should break bad news compassionately, yet sufficiently, so that surrogate and family understand both the gravity of the situation and the lack of long-term benefit of continued life-sustaining interventions. EPs should also help the surrogate and family understand that palliative care addresses comfort needs of the patient including adequate treatment for pain, dyspnea, or anxiety. Part I of this communications model reviews determination of decision-making capacity, surrogacy laws, and advance directives, including legal definitions and application of these steps; Part II (which will appear in a future issue of AEM) covers communication moving from resuscitative to end-of-life and palliative treatment. EPs should recognize acute devastating illness or injuries, when appropriate, as opportunities to initiate end-of-life discussions and to

  12. Are acute subdural hematomas possible without head trauma?

    PubMed Central

    Garbossa, D.; Altieri, R.; Specchia, F. M. Calamo; Agnoletti, A.; Pilloni, G.; Lanotte, M.; Spaziante, R.; Ducati, A.

    2014-01-01

    Acute subdural hematomas (ASDHs) are rarely reported in the literature. In general, it is due to head trauma, but if the traumatic event is very mild, it is inadequate to explain the ASDH occurrence. Risk factors for the development of spontaneous ASDH include hypertension, vascular abnormalities and deficit of coagulation. We present two cases of ASDH in patients with the coagulation deficit and review of the literature to understand the coagulation factors role and platelet role in the management of ASDHs. PMID:25685219

  13. Are acute subdural hematomas possible without head trauma?

    PubMed

    Garbossa, D; Altieri, R; Specchia, F M Calamo; Agnoletti, A; Pilloni, G; Lanotte, M; Spaziante, R; Ducati, A

    2014-01-01

    Acute subdural hematomas (ASDHs) are rarely reported in the literature. In general, it is due to head trauma, but if the traumatic event is very mild, it is inadequate to explain the ASDH occurrence. Risk factors for the development of spontaneous ASDH include hypertension, vascular abnormalities and deficit of coagulation. We present two cases of ASDH in patients with the coagulation deficit and review of the literature to understand the coagulation factors role and platelet role in the management of ASDHs.

  14. Spatial Hotspot Analysis of Acute Myocardial Infarction Events in an Urban Population: A Correlation Study of Health Problems and Industrial Installation

    PubMed Central

    NAMAYANDE, Motahareh Sadat; NEJADKOORKI, Farhad; NAMAYANDE, Seyedeh Mahdieh; DEHGHAN, Hamidreza

    2016-01-01

    Background: The current study’s objectives were to find any possible spatial patterns and hotspot of cardiovascular events and to perform a correlation study to find any possible relevance between cardiovascular disease (CVE) and location of industrial installation said above. Methods: We used the Acute Myocardial Infarction (AMI) hospital admission record in three main hospitals in Yazd, Yazd Province, Iran during 2013, because of CVDs and searched for possible correlation between industries as point-source pollutants and non-random distribution of AMI events. Results: MI incidence rate in Yazd was obtained 531 per 100,000 person-year among men, 458 per 100,000 person-year among women and 783/100,000 person-yr totally. We applied a GIS Hotspot analysis to determine feasible clusters and two sets of clusters were observed. Mean age of 56 AMI events occurred in the cluster cells was calculated as 62.21±14.75 yr. Age and sex as main confounders of AMI were evaluated in the cluster areas in comparison to other areas. We observed no significant difference regarding sex (59% in cluster cells versus 55% in total for men) and age (62.21±14.7 in cluster cells versus 63.28±13.98 in total for men). Conclusion: We found proximity of AMI events cluster to industries installations, and a steel industry, specifically. There could be an association between road-related pollutants and the observed sets of cluster due to the proximity exist between rather crowded highways nearby the events cluster. PMID:27057527

  15. [Vascular dementia].

    PubMed

    Peters, N; Dichgans, M

    2010-10-01

    Vascular dementia (VaD) constitutes the second most frequent cause of dementia following Alzheimer's disease (AD). In contrast to AD, VaD encompasses a variety of conditions and dementia mechanisms including multiple and strategic infarcts, widespread white matter lesions and hemorrhages. The diagnosis of VaD is based on the patient history, the clinical evaluation and neuroimaging. Treatment of VaD should account for the underlying vascular condition and is directed towards the control of vascular risk factors and stroke prevention. The need for early diagnosis and preventive treatment has promoted the concept of vascular cognitive impairment (VCI). Harmonization standards for the description and study of VCI have recently been published. A common and distinct subtype of VaD is subcortical ischemic vascular dementia (SIVD) which is related to cerebral small vessel disease. SIVD is clinically characterized by impairment of executive functions and processing speed with relatively preserved memory. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic variant of SIVD, represents an important differential diagnosis and may serve as a model of SIVD.

  16. Acute adverse events from over-the-counter Chinese herbal medicines: a population-based survey of Hong Kong Chinese

    PubMed Central

    2013-01-01

    Background Although over-the-counter traditional Chinese herbal medicine (COTC) is commonly used to treat everyday illness in many parts of the world, no population-based study has been done to examine the prevalence and factors associated with COTC-related adverse events. Methods A cross-sectional telephone survey was conducted among Hong Kong Chinese adults in 2011 (n = 1100) with informed verbal consent. Stepwise logistic regression of demographic, attitudinal and behavioral variables was used to determine factors associated with past-year adverse events. Results Of study respondents, 71.7% (789/1100) reported past-year COTC use and 2.3% (25/1100) reported at least one COTC-related adverse event in the past year. Of the 27 adverse events cases reported among COTC users, the most common were allergic reactions (n = 11) dizziness (n = 5), and gastro-intestinal problems (n = 4). Pills/capsules were the dosage form that caused the highest proportion of adverse events (n = 10), followed by plasters (n = 7), creams/ointments (n = 5), and ingestible powders (n = 2). Although COTC users reporting adverse events were more likely to report greater practices to avoid adverse events (OR = 6.47; 95% CI: 1.38-30.3); they were also more likely to possess lower education levels (OR = 9.64, 95% CI: 2.20-42.3) and to have received COTC information from non-reliable, mass-media information sources such as magazines (OR = 3.32; 95% CI: 1.01-8.50) or television (OR = 2.93; 95% CI: 1.03-10.7). Package labels were also felt to be unclear by 42.9% of COTC users. A large proportion of COTC users demonstrated low levels of COTC-related knowledge, while the main impediment to greater information-seeking was the belief that reliable COTC information is not obtainable from Western health professionals. Conclusions Despite global movements toward more stringent complementary medicine regulation, the limited accessibility of reliable information

  17. Acute ingestion of a novel whey-derived peptide improves vascular endothelial responses in healthy individuals: a randomized, placebo controlled trial

    PubMed Central

    Ballard, Kevin D; Bruno, Richard S; Seip, Richard L; Quann, Erin E; Volk, Brittanie M; Freidenreich, Daniel J; Kawiecki, Diana M; Kupchak, Brian R; Chung, Min-Yu; Kraemer, William J; Volek, Jeff S

    2009-01-01

    Background Whey protein is a potential source of bioactive peptides. Based on findings from in vitro experiments indicating a novel whey derived peptide (NOP-47) increased endothelial nitric oxide synthesis, we tested its effects on vascular function in humans. Methods A randomized, placebo-controlled, crossover study design was used. Healthy men (n = 10) and women (n = 10) (25 ± 5 y, BMI = 24.3 ± 2.3 kg/m2) participated in two vascular testing days each preceded by 2 wk of supplementation with a single dose of 5 g/day of a novel whey-derived peptide (NOP-47) or placebo. There was a 2 wk washout period between trials. After 2 wk of supplementation, vascular function in the forearm and circulating oxidative stress and inflammatory related biomarkers were measured serially for 2 h after ingestion of 5 g of NOP-47 or placebo. Macrovascular and microvascular function were assessed using brachial artery flow mediated dilation (FMD) and venous occlusion strain gauge plethysmography. Results Baseline peak FMD was not different for Placebo (7.7%) and NOP-47 (7.8%). Placebo had no effect on FMD at 30, 60, and 90 min post-ingestion (7.5%, 7.2%, and 7.6%, respectively) whereas NOP-47 significantly improved FMD responses at these respective postprandial time points compared to baseline (8.9%, 9.9%, and 9.0%; P < 0.0001 for time × trial interaction). Baseline reactive hyperemia forearm blood flow was not different for placebo (27.2 ± 7.2%/min) and NOP-47 (27.3 ± 7.6%/min). Hyperemia blood flow measured 120 min post-ingestion (27.2 ± 7.8%/min) was unaffected by placebo whereas NOP-47 significantly increased hyperemia compared to baseline (29.9 ± 7.8%/min; P = 0.008 for time × trial interaction). Plasma myeloperoxidase was increased transiently by both NOP-47 and placebo, but there were no changes in markers inflammation. Plasma total nitrites/nitrates significantly decreased over the 2 hr post-ingestion period and were lower at 120 min after placebo (-25%) compared to

  18. [The future of vascular medicine].

    PubMed

    Kroeger, K; Luther, B

    2014-10-01

    In the future vascular medicine will still have a great impact on health of people. It should be noted that the aging of the population does not lead to a dramatic increase in patient numbers, but will be associated with a changing spectrum of co-morbidities. In addition, vascular medical research has to include the intensive care special features of vascular patients, the involvement of vascular medicine in a holistic concept of fast-track surgery, a geriatric-oriented intensive monitoring and early geriatric rehabilitation. For the future acceptance of vascular medicine as a separate subject area under delimitation of cardiology and radiology is important. On the other hand, the subject is so complex and will become more complex in future specialisations that mixing of surgery and angiology is desirable, with the aim to preserve the vascular surgical knowledge and skills on par with the medical and interventional measures and further develop them. Only large, interdisciplinary guided vascular centres will be able to provide timely diagnosis and therapy, to deal with the growing multi-morbidity of the patient, to perform complex therapies even in an acute emergency and due to sufficient number of cases to present with well-trained and experienced teams. These requirements are mandatory to decrease patients' mortality step by step.

  19. Acute telogen effluvium onset event is associated with the presence of female androgenetic alopecia: potential therapeutic implications.

    PubMed

    Perez-Mora, Nicolas; Goren, Andy; Velasco, Carlos; Bermudez, Fernando

    2014-01-01

    Acute telogen effluvium (ATE) is often associated with female androgenetic alopecia (FAA), but predictive factors of ATE-FAA association and clinical factors or therapies that may influence the progression of ATE to chronic telogen effluvium (CTE) have not been reported. We have identified predictive factors of ATE-FAA association and retrospectively evaluated the impact of therapies on the progression to CTE. Conclusions are as follows: (i) Triggering cause is a significant independent factor that predicts association of ATE with FAA. (ii) Triggering causes with higher risk of concurrent FAA are severe diet, iron deficiency, and thyroid dysfunction. (iii) Patients suffering ATE may benefit from different therapeutic approaches (depending on which is the triggering cause) to prevent or treat the association with FAA. (iv) Minoxidil use shows a trend to lower the percentage of progression to CTE. (v) Apart from treating the precipitating cause, the different additional oral treatments used have not shown any correlation with progression to CTE. PMID:24850277

  20. Exploring disparities in acute myocardial infarction events between Aboriginal and non-Aboriginal Australians: roles of age, gender, geography and area-level disadvantage.

    PubMed

    Randall, D A; Jorm, L R; Lujic, S; Eades, S J; Churches, T R; O'Loughlin, A J; Leyland, A H

    2014-07-01

    We investigated disparities in rates of acute myocardial infarction (AMI) between Aboriginal and non-Aboriginal people in the 199 Statistical Local Areas (SLAs) in New South Wales, Australia. Using routinely collected and linked hospital and mortality data from 2002 to 2007, we developed multilevel Poisson regression models to estimate the relative rates of first AMI events in the study period accounting for area of residence. Rates of AMI in Aboriginal people were more than two times that in non-Aboriginal people, with the disparity greatest in more disadvantaged and remote areas. AMI rates in Aboriginal people varied significantly by SLA, as did the Aboriginal to non-Aboriginal rate ratio. We identified almost 30 priority areas for universal and targeted preventive interventions that had both high rates of AMI for Aboriginal people and large disparities in rates.

  1. Acute Hematological Effects in Mice Exposed to the Expected Doses, Dose-rates, and Energies of Solar Particle Event-like Proton Radiation

    PubMed Central

    Sanzari, Jenine K.; Cengel, Keith A.; Wan, X. Steven; Rusek, Adam; Kennedy, Ann R.

    2014-01-01

    NASA has funded several projects that have provided evidence for the radiation risk in space. One radiation concern arises from solar particle event (SPE) radiation, which is composed of energetic electrons, protons, alpha particles and heavier particles. SPEs are unpredictable and the accompanying SPE radiation can place astronauts at risk of blood cell death, contributing to a weakened immune system and increased susceptibility to infection. The doses, dose rates, and energies of the proton radiation expected to occur during a SPE have been simulated at the NASA Space Radiation Laboratory, Brookhaven National Laboratory, delivering total body doses to mice. Hematological values were evaluated at acute time points, up to 24 hrs. post-radiation exposure. PMID:25202654

  2. Effect on short- and long-term major adverse cardiac events of statin treatment in patients with acute myocardial infarction and renal dysfunction.

    PubMed

    Lim, Sang Yup; Bae, Eun Hui; Choi, Joon Seok; Kim, Chang Seong; Park, Jeong Woo; Ma, Seong Kwon; Jeong, Myung Ho; Kim, Soo Wan

    2012-05-15

    The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) reduce major adverse cardiac events (MACE) and mortality in patients with acute coronary syndrome. We investigated the effectiveness of statin therapy in reducing MACE in patients with acute myocardial infarction (AMI) and renal dysfunction (RD). In the present retrospective study of 12,853 patients with AMI, the patients were categorized into 4 groups: group I, statin therapy and no RD (estimated glomerular filtration rate ≥60 ml/min/1.73 m(2)); group II, neither statin therapy nor RD; group III, statin therapy and RD; group IV, no statin therapy but RD. The primary end points were death and complications during the hospital course. The secondary end points were MACE during 1 year of follow-up after AMI. Significant differences in the composite MACE during 12 months of follow-up were observed among the 4 groups (group I, 11.7%; group II, 19.0%; group III, 26.7%; and group IV, 45.5%; p <0.001). In a Cox proportional hazards model, mortality at 12 months increased stepwise from group II to IV compared to group I. Moreover, MACE-free survival in the severe RD group (estimated glomerular filtration rate <30 mL/min/1.73 m(2)) was also greater in the statin-treated group. In conclusion, statin therapy reduced MACE at 1 year of follow-up in patients with AMI regardless of RD.

  3. A bypass case due to an acute inferior myocardial infarction caused by vascular occlusion of the left subclavian artery and left anterior descending artery

    PubMed Central

    Altas, Yakup; Ulugg, Ali Veysel

    2016-01-01

    ST segment elevation is the most common electrocardiographic finding in acute myocardial infarction. ST elevation in chest leads generally represents left anterior descending artery occlusion, while elevation in DII and III, and aVF represents right coronary and circumflex artery occlusion. A female patient aged 66 years was admitted to our emergency service with ST elevation in leads DIII and aVF. A diagnosis of acute inferior myocardial infarction was made. The patient’s history included coronary artery bypass graft involving the left internal mammary artery to the left anterior descending coronary artery and aorta to the right coronary artery. The patient was taken to the cardiac catheterization laboratory for primary percutaneous coronary intervention and a lesion in the left anterior descending artery was identified. Additionally, the left subclavian artery was totally occluded. Following intervention to the lesion, the patient was discharged on day 4 of admission. PMID:27555777

  4. A bypass case due to an acute inferior myocardial infarction caused by vascular occlusion of the left subclavian artery and left anterior descending artery.

    PubMed

    Altas, Yakup; Ulugg, Ali Veysel

    2016-01-01

    ST segment elevation is the most common electrocardiographic finding in acute myocardial infarction. ST elevation in chest leads generally represents left anterior descending artery occlusion, while elevation in DII and III, and aVF represents right coronary and circumflex artery occlusion. A female patient aged 66 years was admitted to our emergency service with ST elevation in leads DIII and aVF. A diagnosis of acute inferior myocardial infarction was made. The patient's history included coronary artery bypass graft involving the left internal mammary artery to the left anterior descending coronary artery and aorta to the right coronary artery. The patient was taken to the cardiac catheterization laboratory for primary percutaneous coronary intervention and a lesion in the left anterior descending artery was identified. Additionally, the left subclavian artery was totally occluded. Following intervention to the lesion, the patient was discharged on day 4 of admission. PMID:27555777

  5. Vascular emergencies.

    PubMed

    Semashko, D C

    1997-01-01

    This article reviews the initial assessment and emergent management of several common as well as uncommon vascular emergencies. Aortic dissection, aneurysms, and arterial occlusive disease are familiar but challenging clinical entities. Less frequently encountered conditions are also discussed including an aortic enteric fistula, mesenteric venous thrombosis, phlegmasia alba dolens, and subclavian vein thrombosis.

  6. An Acute Abdominal Catastrophe in a HIV Positive Patient

    PubMed Central

    Gaduputi, Vinaya; Patel, Harish; Vootla, Vamshidhar; Khan, Usman; Chilimuri, Sridhar

    2012-01-01

    We report this case of a 45-year-old man with HIV-AIDS on HAART therapy who presented with acute abdominal pain and renal failure. He was found to have pneumatosis intestinalis on computerized axial tomography scan of the abdomen. He underwent emergent explorative laparotomy, which revealed a necrotic large bowel segment for which a right-sided hemicolectomy and ileostomy were performed. The patient subsequently developed septic shock and hypoxic respiratory failure. He expired a week after the surgical procedure. Acute abdominal events due to vascular catastrophes secondary to hypercoagulability, endothelial dysfunction and accelerated atherosclerosis have been reported in HIV positive patients.

  7. Identifying Drug (Cocaine) Intake Events from Acute Physiological Response in the Presence of Free-living Physical Activity

    PubMed Central

    Hossain, Syed Monowar; Ali, Amin Ahsan; Rahman, Mahbubur; Ertin, Emre; Epstein, David; Kennedy, Ashley; Preston, Kenzie; Umbricht, Annie; Chen, Yixin; Kumar, Santosh

    2014-01-01

    A variety of health and behavioral states can potentially be inferred from physiological measurements that can now be collected in the natural free-living environment. The major challenge, however, is to develop computational models for automated detection of health events that can work reliably in the natural field environment. In this paper, we develop a physiologically-informed model to automatically detect drug (cocaine) use events in the free-living environment of participants from their electrocardiogram (ECG) measurements. The key to reliably detecting drug use events in the field is to incorporate the knowledge of autonomic nervous system (ANS) behavior in the model development so as to decompose the activation effect of cocaine from the natural recovery behavior of the parasympathetic nervous system (after an episode of physical activity). We collect 89 days of data from 9 active drug users in two residential lab environments and 922 days of data from 42 active drug users in the field environment, for a total of 11,283 hours. We develop a model that tracks the natural recovery by the parasympathetic nervous system and then estimates the dampening caused to the recovery by the activation of the sympathetic nervous system due to cocaine. We develop efficient methods to screen and clean the ECG time series data and extract candidate windows to assess for potential drug use. We then apply our model on the recovery segments from these windows. Our model achieves 100% true positive rate while keeping the false positive rate to 0.87/day over (9+ hours/day of) lab data and to 1.13/day over (11+ hours/day of) field data. PMID:25531010

  8. Experimental Branch Retinal Vein Occlusion Induces Upstream Pericyte Loss and Vascular Destabilization

    PubMed Central

    Dominguez, Elisa; Raoul, William; Calippe, Bertrand; Sahel, José-Alain; Guillonneau, Xavier; Paques, Michel; Sennlaub, Florian

    2015-01-01

    Aims Branch retinal vein occlusion (BRVO) leads to extensive vascular remodeling and is important cause of visual impairment. Although the vascular morphological changes following experimental vein occlusion have been described in a variety of models using angiography, the underlying cellular events are ill defined. Methods and Results We here show that laser-induced experimental BRVO in mice leads to a wave of TUNEL-positive endothelial cell (EC) apoptosis in the upstream vascular network associated with a transient edema and hemorrhages. Subsequently, we observe an induction of EC proliferation within the dilated vein and capillaries, detected by EdU incorporation, and the edema resolves. However, the pericytes of the upstream capillaries are severely reduced, which was associated with continuing EC apoptosis and proliferation. The vascular remodeling was associated with increased expression of TGFβ, TSP-1, but also FGF2 expression. Exposure of the experimental animals to hypoxia, when pericyte (PC) dropout had occurred, led to a dramatic increase in endothelial cell proliferation, confirming the vascular instability induced by the experimental BRVO. Conclusion Experimental BRVO leads to acute endothelial cells apoptosis and increased permeability. Subsequently the upstream vascular network remains destabilized, characterized by pericyte dropout, un-physiologically high endothelial cells turnover and sensitivity to hypoxia. These early changes might pave the way for capillary loss and subsequent chronic ischemia and edema that characterize the late stage disease. PMID:26208283

  9. Prediction of fatal or near-fatal cardiac arrhythmia events in patients with depressed left ventricular function after an acute myocardial infarction†

    PubMed Central

    Huikuri, Heikki V.; Raatikainen, M.J. Pekka; Moerch-Joergensen, Rikke; Hartikainen, Juha; Virtanen, Vesa; Boland, Jean; Anttonen, Olli; Hoest, Nis; Boersma, Lucas V.A.; Platou, Eivind S.; Messier, Marc D.; Bloch-Thomsen, Poul-Erik

    2009-01-01

    Aims To determine whether risk stratification tests can predict serious arrhythmic events after acute myocardial infarction (AMI) in patients with reduced left ventricular ejection fraction (LVEF ≤ 0.40). Methods and results A total of 5869 consecutive patients were screened in 10 European centres, and 312 patients (age 65 ± 11 years) with a mean LVEF of 31 ± 6% were included in the study. Heart rate variability/turbulence, ambient arrhythmias, signal-averaged electrocardiogram (SAECG), T-wave alternans, and programmed electrical stimulation (PES) were performed 6 weeks after AMI. The primary endpoint was ECG-documented ventricular fibrillation or symptomatic sustained ventricular tachycardia (VT). To document these arrhythmic events, the patients received an implantable ECG loop-recorder. There were 25 primary endpoints (8.0%) during the follow-up of 2 years. The strongest predictors of primary endpoint were measures of heart rate variability, e.g. hazard ratio (HR) for reduced very-low frequency component (<5.7 ln ms2) adjusted for clinical variables was 7.0 (95% CI: 2.4–20.3, P < 0.001). Induction of sustained monomorphic VT during PES (adjusted HR = 4.8, 95% CI, 1.7–13.4, P = 0.003) also predicted the primary endpoint. Conclusion Fatal or near-fatal arrhythmias can be predicted by many risk stratification methods, especially by heart rate variability, in patients with reduced LVEF after AMI. PMID:19155249

  10. The effect of solar-geomagnetic activity during hospital admission on coronary events within 1 year in patients with acute coronary syndromes

    NASA Astrophysics Data System (ADS)

    Vencloviene, J.; Babarskiene, R.; Milvidaite, I.; Kubilius, R.; Stasionyte, J.

    2013-12-01

    Some evidence indicates the deterioration of the cardiovascular system during space storms. It is plausible that the space weather conditions during and after hospital admission may affect the risk of coronary events in patients with acute coronary syndromes (ACS). We analyzed the data of 1400 ACS patients who were admitted to the Hospital Lithuanian University of Health Sciences, and who survived for more than 4 days. We evaluated the associations between geomagnetic storms (GS), solar proton events (SPE), and solar flares (SF) that occurred 0-3 days before and after hospital admission and the risk of cardiovascular death (CAD), non-fatal ACS, and coronary artery bypass grafting (CABG) during a period of 1 year; the evaluation was based on the multivariate logistic model, controlling for clinical data. After adjustment for clinical variables, GS occurring in conjunction with SF 1 day before admission increased the risk of CAD by over 2.5 times. GS 2 days after SPE occurred 1 day after admission increased the risk of CAD and CABG by over 2.8 times. The risk of CABG increased by over 2 times in patients admitted during the day of GS and 1 day after SPE. The risk of ACS was by over 1.63 times higher for patients admitted 1 day before or after solar flares.

  11. Phylogenetic evidence for intratypic recombinant events in a novel human adenovirus C that causes severe acute respiratory infection in children

    PubMed Central

    Wang, Yanqun; Li, Yamin; Lu, Roujian; Zhao, Yanjie; Xie, Zhengde; Shen, Jun; Tan, Wenjie

    2016-01-01

    Human adenoviruses (HAdVs) are prevalent in hospitalized children with severe acute respiratory infection (SARI). Here, we report a unique recombinant HAdV strain (CBJ113) isolated from a HAdV-positive child with SARI. The whole-genome sequence was determined using Sanger sequencing and high-throughput sequencing. A phylogenetic analysis of the complete genome indicated that the CBJ113 strain shares a common origin with HAdV-C2, HAdV-C6, HAdV-C1, HAdV-C5, and HAdV-C57 and formed a novel subclade on the same branch as other HAdV-C subtypes. BootScan and single nucleotide polymorphism analyses showed that the CBJ113 genome has an intra-subtype recombinant structure and comprises gene regions mainly originating from two circulating viral strains: HAdV-1 and HAdV-2. The parental penton base, pVI, and DBP genes of the recombinant strain clustered with the HAdV-1 prototype strain, and the E1B, hexon, fiber, and 100 K genes of the recombinant clustered within the HAdV-2 subtype, meanwhile the E4orf1 and DNA polymerase genes of the recombinant shared the greatest similarity with those of HAdV-5 and HAdV-6, respectively. All of these findings provide insight into our understanding of the dynamics of the complexity of the HAdV-C epidemic. More extensive studies should address the pathogenicity and clinical characteristics of the novel recombinant. PMID:26960434

  12. Vascular calcification: Mechanisms of vascular smooth muscle cell calcification.

    PubMed

    Leopold, Jane A

    2015-05-01

    Vascular calcification is highly prevalent and, when present, is associated with major adverse cardiovascular events. Vascular smooth muscle cells play an integral role in mediating vessel calcification by undergoing differentiation to osteoblast-like cells and generating matrix vesicles that serve as a nidus for calcium-phosphate deposition in the vessel wall. Once believed to be a passive process, it is now recognized that vascular calcification is a complex and highly regulated process that involves activation of cellular signaling pathways, circulating inhibitors of calcification, genetic factors, and hormones. This review will examine several of the key mechanisms linking vascular smooth muscle cells to vessel calcification that may be targeted to reduce vessel wall mineralization and, thereby, reduce cardiovascular risk.

  13. Neurobiology of Vascular Dementia

    PubMed Central

    Enciu, Ana-Maria; Constantinescu, Stefan N.; Popescu, Laurenţiu M.; Mureşanu, Dafin F.; Popescu, Bogdan O.

    2011-01-01

    Vascular dementia is, in its current conceptual form, a distinct type of dementia with a spectrum of specific clinical and pathophysiological features. However, in a very large majority of cases, these alterations occur in an already aged brain, characterized by a milieu of cellular and molecular events common for different neurodegenerative diseases. The cell signaling defects and molecular dyshomeostasis might lead to neuronal malfunction prior to the death of neurons and the alteration of neuronal networks. In the present paper, we explore some of the molecular mechanisms underlying brain malfunction triggered by cerebrovascular disease and risk factors. We suggest that, in the age of genetic investigation and molecular diagnosis, the concept of vascular dementia needs a new approach. PMID:21876809

  14. Difference of intensity and disparity in impact of climate on several vascular diseases.

    PubMed

    Ishikawa, Kiyotake; Niwa, Manabu; Tanaka, Toshikazu

    2012-01-01

    Several studies have reported the correlation between regional weather patterns and various vascular diseases. However, each vascular disease has inherent characteristics, and the difference of meteorological correlation between these diseases is not well known. This study was aimed at investigating the disparity and intensity of the relationship between meteorological factors and various vascular diseases. A total of 1113 events within 2 years were included in this study. Daily meteorological parameters with and without events were, respectively, compared in acute coronary syndrome (ACS), cerebral infarction (CI), cerebral embolism (CE), cerebral hemorrhage (CH), subarachnoid hemorrhage (SAH), aortic dissection (AD), and aortic aneurysm rupture (AAR). Days with CI onset correlated with fewer sunshine hours, fewer solar radiation factors, greater amounts of precipitation factors, and more humidity factors, whereas CH and CE only showed lower correlation in temperature factors. However, there was no relation seen between ACS, SAH, AD, AAR, and climatic parameters. Our findings suggest that climate affects various cardiovascular and cerebrovascular diseases differently. This finding may help in understanding the mechanism of how vascular events are triggered.

  15. Altered gene expression in T-cell receptor signalling in peripheral blood leucocytes in acute coronary syndrome predicts secondary coronary events

    PubMed Central

    Takashima, Shin-ichiro; Usui, Soichiro; Kurokawa, Keisuke; Kitano, Teppei; Kato, Takeshi; Murai, Hisayoshi; Furusho, Hiroshi; Oda, Hiroyuki; Maruyama, Michiro; Nagata, Yoshiki; Usuda, Kazuo; Kubota, Koji; Takeshita, Yumie; Sakai, Yoshio; Honda, Masao; Kaneko, Shuichi; Takamura, Masayuki

    2016-01-01

    Objective Comprehensive profiling of gene expression in peripheral blood leucocytes (PBLs) in patients with acute coronary syndrome (ACS) as a prognosticator is needed. We explored the specific profile of gene expression in PBLs in ACS for long-term risk stratification. Methods 30 patients with ACS who underwent primary percutaneous coronary intervention (PCI) and 15 age-matched adults who participated in medical check-ups were enrolled from three centres. Peripheral blood samples were collected to extract RNA for microarray analyses. Results During the 5-year follow-up, 36% of this cohort developed the expected non-fatal coronary events (NFEs) of target lesion revascularisation (TLR) and PCI for a de novo lesion. Class comparison analysis (p<0.005) demonstrated that 83 genes among 7785 prefiltered genes (41 upregulated vs 42 downregulated genes) were extracted to classify the patients according to the occurrence of NFE. Pathway analysis based on gene ontology revealed that the NFEs were associated with altered gene expression regarding the T-cell receptor signalling pathway in ACS. Univariate t test showed that the expression level of death-associated protein kinase1 (DAPK1), known to regulate inflammation, was the most significantly negatively regulated gene in the event group (0.61-fold, p<0.0005). Kaplan-Meier curve analysis and multivariate analysis adjusted for baseline characteristics or clinical biomarkers demonstrated that lower DAPK1 expression in PBL emerged as an independent risk factor for the NFEs (HR: 8.73; CI 1.05 to 72.8, p=0.045). Conclusions Altered gene expression in T-cell receptor signalling in PBL in ACS could be a prognosticator for secondary coronary events. Trial registration number UMIN000001932; Results. PMID:27403330

  16. Association of Lower Fractional Flow Reserve Values With Higher Risk of Adverse Cardiac Events for Lesions Deferred Revascularization Among Patients With Acute Coronary Syndrome

    PubMed Central

    Masrani Mehta, Shriti; Depta, Jeremiah P; Novak, Eric; Patel, Jayendrakumar S; Patel, Yogesh; Raymer, David; Facey, Gabrielle; Zajarias, Alan; Lasala, John M; Singh, Jasvindar; Bach, Richard G; Kurz, Howard I

    2015-01-01

    Background The safety of deferring revascularization based on fractional flow reserve (FFR) during acute coronary syndrome (ACS) is unclear. We evaluated the association of FFR and adverse cardiac events among patients with coronary lesions deferred revascularization based on FFR in the setting of ACS versus non-ACS. Methods and Results The study population (674 patients; 816 lesions) was divided into ACS (n=334) and non-ACS (n=340) groups based on the diagnosis when revascularization was deferred based on FFR values >0.80 between October 2002 and July 2010. The association and interaction between FFR and clinical outcomes was evaluated using Cox proportional hazards models within each group (mean follow-up of 4.5±2.1 years). Subsequent revascularization of a deferred lesion was classified as a deferred lesion intervention (DLI), whereas the composite of DLI or myocardial infarction (MI) attributed to a deferred lesion was designated as deferred lesion failure (DLF). In the non-ACS group, lower FFR values were not associated with any increase in adverse cardiac events. In the ACS group, every 0.01 decrease in FFR was associated with a significantly higher rate of cardiovascular death, MI, or DLI (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.03 to 1.12), MI or DLI (HR, 1.09; 95% CI: 1.04 to 1.14), DLF (HR, 1.12; 95% CI, 1.06 to 1.18), MI (HR, 1.07; 95% CI, 1.00 to 1.14), and DLI (HR, 1.12; 95% CI, 1.06 to 1.18). Conclusion Lower FFR values among ACS patients with coronary lesions deferred revascularization based on FFR are associated with a significantly higher rate of adverse cardiac events. This association was not observed in non-ACS patients. PMID:26289346

  17. PTEN permits acute increases in D3-phosphoinositide levels following TCR stimulation but inhibits distal signaling events by reducing the basal activity of Akt.

    PubMed

    Seminario, Maria-Cristina; Precht, Patricia; Bunnell, Stephen C; Warren, Sarah E; Morris, Christa M; Taub, Dennis; Wange, Ronald L

    2004-11-01

    Phosphoinositide 3-kinase (PI3K) is important in TCR signaling. PI3K generates phosphatidylinositol 3, 4, 5-trisphosphate (PI-3,4,5-P3), which regulates membrane localization and/or activity of multiple signaling proteins. PTEN (phosphatase and tensin homologue deleted on chromosome 10) opposes PI3K, reversing this reaction. Maintaining the balance between these two enzymes is important for normal T cell function. Here we use the PTEN-null Jurkat T cell line to address the role of PTEN in modulating proximal and distal TCR-signaling events. PTEN expression at levels that restored low basal Akt phosphorylation (an indicator of PI-3,4,5-P3 levels), but which were not themselves cytotoxic, had minimal effect on TCR-stimulated activation of phospholipase Cgamma1 and Ca2+ flux, but reduced the duration of extracellular signal-regulated kinase (Erk) activation. Distal signaling events, including nuclear factor of activated T cells (NFAT) activation, CD69 expression and IL-2 production, were all inhibited by PTEN expression. Notably, PTEN did not block TCR-stimulated PI-3,4,5-P3 accumulation. The effect of PTEN on distal TCR signaling events was strongly correlated with the loss of the constitutive Akt activation and glycogen synthase kinase-3 (GSK3) inhibition that is typical of Jurkat cells, and could be reversed by expression of activated Akt or pharmacologic inhibition of GSK3. These results suggest that PTEN acts in T cells primarily to control basal PI-3,4,5-P3 levels, rather than opposing PI3K acutely during TCR stimulation.

  18. Left Ventricular Diastolic Dysfunction in Ischemic Stroke: Functional and Vascular Outcomes

    PubMed Central

    Park, Hong-Kyun; Kim, Beom Joon; Yoon, Chang-Hwan; Yang, Mi Hwa; Han, Moon-Ku; Bae, Hee-Joon

    2016-01-01

    Background and Purpose Left ventricular (LV) diastolic dysfunction, developed in relation to myocardial dysfunction and remodeling, is documented in 15%-25% of the population. However, its role in functional recovery and recurrent vascular events after acute ischemic stroke has not been thoroughly investigated. Methods In this retrospective observational study, we identified 2,827 ischemic stroke cases with adequate echocardiographic evaluations to assess LV diastolic dysfunction within 1 month after the index stroke. The peak transmitral filling velocity/mean mitral annular velocity during early diastole (E/e’) was used to estimate LV diastolic dysfunction. We divided patients into 3 groups according to E/e’ as follows: <8, 8-15, and ≥15. Recurrent vascular events and functional recovery were prospectively collected at 3 months and 1 year. Results Among included patients, E/e’ was 10.6±6.4: E/e’ <8 in 993 (35%), 8-15 in 1,444 (51%), and ≥15 in 378 (13%) cases. Functional dependency or death (modified Rankin Scale score ≥2) and composite vascular events were documented in 1,298 (46%) and 187 (7%) patients, respectively, at 3 months. In multivariable analyses, ischemic stroke cases with E/e’ ≥15 had increased odds of functional dependence or death at 3 months (adjusted OR [95% CI]: 1.73 [1.27-2.35]) or 1 year (1.47 [1.06-2.06]) and vascular events within 1 year (1.65 [1.08-2.51]). Subgroups with normal ejection fraction or sinus rhythm exhibited a similar overall pattern and direction. Conclusions LV diastolic dysfunction was associated with poor functional outcomes and composite vascular events up to 1 year. PMID:27283279

  19. The Effects of Acute Dopamine Precursor Depletion on the Cognitive Control Functions of Performance Monitoring and Conflict Processing: An Event-Related Potential (ERP) Study

    PubMed Central

    Primosch, Mark; Leyton, Marco; Steffensen, Scott C.

    2015-01-01

    Studies using medications and psychiatric populations implicate dopamine in cognitive control and performance monitoring processes. However, side effects associated with medication or studying psychiatric groups may confound the relationship between dopamine and cognitive control. To circumvent such possibilities, we utilized a randomized, double-blind, placebo-controlled, within-subjects design wherein participants were administered a nutritionally-balanced amino acid mixture (BAL) and an amino acid mixture deficient in the dopamine precursors tyrosine (TYR) and phenylalanine (PHE) on two separate occasions. Order of sessions was randomly assigned. Cognitive control and performance monitoring were assessed using response times (RT), error rates, the N450, an event-related potential (ERP) index of conflict monitoring, the conflict slow potential (conflict SP), an ERP index of conflict resolution, and the error-related negativity (ERN) and error positivity (Pe), ERPs associated with performance monitoring. Participants were twelve males who completed a Stroop color-word task while ERPs were collected four hours following acute PHE and TYR depletion (APTD) or balanced (BAL) mixture ingestion in two separate sessions. N450 and conflict SP ERP amplitudes significantly differentiated congruent from incongruent trials, but did not differ as a function of APTD or BAL mixture ingestion. Similarly, ERN and Pe amplitudes showed significant differences between error and correct trials that were not different between APTD and BAL conditions. Findings indicate that acute dopamine precursor depletion does not significantly alter cognitive control and performance monitoring ERPs. Current results do not preclude the role of dopamine in these processes, but suggest that multiple methods for dopamine-related hypothesis testing are needed. PMID:26492082

  20. Promoting engagement by patients and families to reduce adverse events in acute care settings: a systematic review

    PubMed Central

    Berger, Zackary; Flickinger, Tabor E; Pfoh, Elizabeth; Martinez, Kathryn A; Dy, Sydney M

    2014-01-01

    Introduction Patient-centeredness is central to healthcare. Hospitals should address patients’ unique needs to improve safety and quality. Patient engagement in healthcare, which may help prevent adverse events, can be approached as an independent patient safety practice (PSP) or as part of a multifactorial PSP. Objectives This review examines how interventions encouraging this engagement have been implemented in controlled trials. Methods We searched Medline, CINAHL, Embase and Cochrane from 2000 to 2012 for English language studies in hospital settings with prospective controlled designs, addressing the effectiveness or implementation of patient/family engagement in PSPs. We separately reviewed interventions implemented as part of selected broader PSPs by way of example: hand hygiene, ventilator-associated pneumonia, rapid response systems and care transitions. Results Six articles met the inclusion criteria for effectiveness with a primary focus on patient engagement. We identified 12 studies implementing patient engagement as an aspect of selected broader PSPs. A number of studies relied on patients’ possible function as a reporter of error to healthcare workers and patients as a source of reminders regarding safety behaviours, while others relied on direct activation of patients or families. Definitions of patient and family engagement were lacking, as well as evidence regarding the types of patients who might feel comfortable engaging with providers, and in what contexts. Conclusions While patient engagement in safety is appealing, there is insufficient high-quality evidence informing real-world implementation. Further work should evaluate the effectiveness of interventions on patient and family engagement and clarify the added benefit of incorporating engagement in multifaceted approaches to improve patient safety endpoints. In addition, strategies to assess and overcome barriers to patients’ willingness to actively engage in their care should be

  1. Immune activation and viral burden in acute disease induced by simian immunodeficiency virus SIVsmmPBj14: correlation between in vitro and in vivo events.

    PubMed Central

    Schwiebert, R; Fultz, P N

    1994-01-01

    The simian immunodeficiency virus SIVsmmPBj14 (SIV-PBj14) is an atypical lentivirus that causes acute disease and death in pig-tailed macaques and in vitro replicates efficiently in resting macaque lymphocytes and activates and induces proliferation of lymphocytes. The present study was conducted to test the hypothesis that production of large quantities of SIV-PBj14 induces widespread immune activation and elaboration of cytokines which lead directly to the death of infected pig-tailed macaques. Following intravenous inoculation of pig-tailed macaques with SIV-PBj14, acute disease developed and was characterized by high levels of plasma viremia, p27gag antigenemia, tumor necrosis factor alpha, and interleukin-6 (IL-6). All animals died within 10 days of infection, at which time some animals had as many as 100% CD4+ cells in the periphery and lymphoid tissues infected. During the last few days before death, titers of infectious virus in blood increased as much as 10(5)-fold. By using dual-label immunofluorescence assays for detection of cell surface activation markers, both CD4+ and CD8+ lymphocytes were shown to express the IL-2 and transferrin receptors following either in vivo or in vitro infection with SIV-PBj14. Furthermore, in vitro infection of quiescent macaque lymphocytes by SIV-PBj14 was accompanied by proliferation of both CD4+ and CD8+ lymphocyte subsets, as measured by incorporation of [3H]thymidine. Increases in numbers of activated lymphocytes and levels of proinflammatory cytokines in plasma coincided with increased amounts of detectable virus in vivo. Clinical signs of disease and pathologic findings were most consistent with death from a shock-like syndrome, in which acute-phase inflammatory cytokines are known to play a major role. Tumor necrosis factor alpha, IL-2, and IL-6 were detected in some cultures infected with SIV-PBj14, but this finding was not consistent. When cytokines were detected, their concentrations were essentially no different

  2. Hypertension and acute myocardial infarction: an overview.

    PubMed

    Pedrinelli, Roberto; Ballo, Piercarlo; Fiorentini, Cesare; Denti, Silvia; Galderisi, Maurizio; Ganau, Antonello; Germanò, Giuseppe; Innelli, Pasquale; Paini, Anna; Perlini, Stefano; Salvetti, Massimo; Zacà, Valerio

    2012-03-01

    History of hypertension is a frequent finding in patients with acute myocardial infarction (AMI) and its recurring association with female sex, diabetes, older age, less frequent smoking and more frequent vascular comorbidities composes a risk profile quite distinctive from the normotensive ischemic counterpart.Antecedent hypertension associates with higher rates of death and morbid events both during the early and long-term course of AMI, particularly if complicated by left ventricular dysfunction and/or congestive heart failure. Renin-angiotensin-aldosterone system blockade, through either angiotensin-converting enzyme inhibition, angiotensin II receptor blockade or aldosterone antagonism, exerts particular benefits in that high-risk hypertensive subgroup.In contrast to the negative implications carried by antecedent hypertension, higher systolic pressure at the onset of chest pain associates with lower mortality within 1 year from coronary occlusion, whereas increased blood pressure recorded after hemodynamic stabilization from the acute ischemic event bears inconsistent relationships with recurring coronary events in the long-term follow-up.Whether antihypertensive treatment in post-AMI hypertensive patients prevents ischemic relapses is uncertain. As a matter of fact, excessive diastolic pressure drops may jeopardize coronary perfusion and predispose to new acute coronary events, although the precise cause-effect mechanisms underlying this phenomenon need further evaluation. PMID:22317927

  3. Results From the Periodontitis and Vascular Events (PAVE) Study: A Pilot Multicentered, Randomized, Controlled Trial to Study Effects of Periodontal Therapy in a Secondary Prevention Model of Cardiovascular Disease

    PubMed Central

    Offenbacher, Steven; Beck, James D.; Moss, Kevin; Mendoza, Luisito; Paquette, David W.; Barrow, David A.; Couper, David J.; Stewart, Dawn D.; Falkner, Karen L.; Graham, Susan P.; Grossi, Sara; Gunsolley, John C.; Madden, Theresa; Maupome, Gerardo; Trevisan, Maurizio; Van Dyke, Thomas E.; Genco, Robert J.

    2009-01-01

    Background In the Periodontitis and Vascular Events (PAVE) pilot study, periodontal therapy was provided as an intervention in a secondary cardiac event prevention model through five coordinated cardiac– dental centers. Methods Subjects were randomized to either community care or protocol provided scaling and root planing to evaluate effects on periodontal status and systemic levels of high-sensitivity C-reactive protein (hs-CRP). Results After 6 months, there was a significant reduction in mean probing depth and extent of 4- or 5-mm pockets. However, there were no significant differences in attachment levels, bleeding upon probing, or extent of subgingival calculus comparing subjects assigned to protocol therapy (n = 151) to those assigned to community care (n = 152). Using intent-to-treat analyses, there was no significant effect on serum hs-CRP levels at 6 months. However, 48% of the subjects randomized to community care received preventive or periodontal treatments. Secondary analyses demonstrated that consideration of any preventive or periodontal care (i.e., any treatment) compared to no treatment showed a significant reduction in the percentage of people with elevated hs-CRP (values >3 mg/l) at 6 months. However, obesity nullified the periodontal treatment effects on hs-CRP reduction. The adjusted odds ratio for hs-CRP levels >3 mg/l at 6 months for any treatment versus no treatment among non-obese individuals was 0.26 (95%confidence interval: 0.09 to 0.72), adjusting for smoking, marital status, and gender. Conclusion This pilot study demonstrated the critical role of considering obesity as well as rigorous preventive and periodontal care in trials designed to reduce cardiovascular risk. PMID:19186958

  4. The Vascular Effects of Infection in Pediatric Stroke (VIPS) Study

    PubMed Central

    Fullerton, Heather J.; Elkind, Mitchell S. V.; Barkovich, James A.; Glaser, Carol; Glidden, David; Hills, Nancy K.; Leiva-Salinas, Carlos; Wintermark, Max; deVeber, Gabrielle A.

    2012-01-01

    Background The most common cause of arterial ischemic stroke (AIS) in a previously healthy child is a large vessel cerebral arteriopathy. Varicella zoster virus is an established etiology, and recent data implicate a non-specific effect of additional common viral infections on cerebral vessels. The Vascular effects of Infection in Pediatric Stroke (VIPS) study is a multicenter cohort study that will test the hypotheses that (1) infection can lead to childhood AIS by causing vascular injury, and (2) the resultant arteriopathy, and inflammatory markers, predict recurrent stroke. Methods We are prospectively enrolling 480 children (aged 1 month through 18 years) with AIS and collecting (1) extensive infectious histories (through parental interview), (2) blood and serum samples (and CSF, when clinically obtained), and (3) clinically obtained but standardized brain and cerebrovascular imaging studies. Imaging studies are being centrally reviewed and adjudicated. Centralized laboratory assays will include serologies (acute and convalescent) and molecular assays for herpes viruses, and levels of inflammatory markers. Subjects are followed prospectively for recurrent ischemic events for the duration of the study (minimum of 1 year). We are banking biological specimens (including DNA) for future studies of specific infectious agents and mediators of inflammation relevant to thrombosis and vascular injury. Analysis Plan In a cross-sectional analysis, we will use logistic regression techniques to measure the association between markers of infection (from the clinical history and laboratory assays) and cerebral arteriopathy. In a prospective cohort analysis, we will use survival analysis techniques to determine whether cerebral arteriopathy and inflammatory markers predict recurrent stroke. Conclusions VIPS will shed light on the vascular effects of infection in childhood stroke. Because arteriopathy is likely the major predictor of recurrent stroke in children, a better

  5. 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

  6. A platelet P-selectin test predicts adverse cardiovascular events in patients with acute coronary syndromes treated with aspirin and clopidogrel.

    PubMed

    Thomas, Mark R; Wijeyeratne, Yanushi D; May, Jane A; Johnson, Andrew; Heptinstall, Stan; Fox, Susan C

    2014-01-01

    There is wide variation in response to antiplatelet therapy and high on-treatment platelet reactivity is associated with adverse cardiovascular events. The objective here was to determine whether the results of a novel strategy for assessing platelet reactivity (based on P-selectin measurement) are associated with clinical outcomes in patients with acute coronary syndromes (ACS). This was a prospective cohort study of 100 ACS patients taking aspirin and clopidogrel. P-selectin tests designed to assess response to P2Y12 antagonists or aspirin were performed alongside light transmission aggregometry. For the P2Y12 P-selectin test, an optimal cutoff for high platelet reactivity was determined by receiver operating characteristic (ROC) curve analysis. Patients were divided into two cohorts based on this value: patients with (n = 42) or without (n = 58) high platelet reactivity. The primary endpoint was defined as the composite of cardiovascular death, myocardial infarction and stent thrombosis. After 12 months, the primary endpoint occurred in 12 patients. ROC curve analysis determined that the P2Y12 P-selectin test results were predictive of the primary endpoint (area under curve = 0.69, p = 0.046). The primary endpoint occurred more frequently in patients with high on-treatment platelet reactivity compared to those without (21.4% vs. 5.2%; hazard ratio (HR) 4.14; p = 0.026). The P2Y12 P-selectin test results correlated with light transmission aggregometry (Spearman p < 0.0001). Using the Aspirin P-selectin test, only two patients demonstrated high on-treatment platelet reactivity. This study suggests that a P2Y12 P-selectin test is capable of detecting high on-treatment platelet reactivity, which is associated with subsequent cardiovascular events.

  7. Inflammatory cytokines imbalance in the very early phase of acute coronary syndrome: correlations with angiographic findings and in-hospital events.

    PubMed

    Brunetti, Natale Daniele; Munno, Irene; Pellegrino, Pier Luigi; Ruggero, Vincenzo; Correale, Michele; De Gennaro, Luisa; Cuculo, Andrea; Campanale, Erasmo Giulio; Di Biase, Matteo

    2011-02-01

    The aim of this study is to investigate the release of some inflammatory cytokines (Cks) during the very early phase (first 24 h) of acute coronary syndrome (ACS). Twenty-six consecutive subjects admitted to coronary care unit with ACS underwent serial blood sampling in order to evaluate concentrations of interleukin (IL)-2, IL-10, IL-18, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. Blood samples were taken within 6 h after onset of chest pain (T₀), at 12 h (T₁), and at 24 h (T₂). Patients were thus divided into four groups comparing pro-inflammatory Ck release (IL-2, TNF-α, and IFN-γ) and anti-inflammatory activity (IL-10). Clinical features, risk factors, incidence of adverse events, and coronary angiography findings were compared with Ck activation. Ck levels were significantly increased if compared with baseline. Subjects with marked inflammatory response showed a higher incidence of left anterior descending coronary disease (IL-2, p < 0.001; TNF-α and IFN-γ, p < 0.05) and more often incurred early complications (IL-2, p < 0.05; IFN-γ, p < 0.001). A correlation was detectable between IL-18 levels and myocardial enzyme release (creatine kinase, r = 0.47; lactate dehydrogenase, r = 0.54; troponin I, r = 0.58; p < 0.05). TNF-α levels were associated with a worse prognosis at follow-up (Log rank, p < 0.05). A Ck activation characterizes the early phase of ACS. Early inflammatory reaction seems to correlate with coronary disease and adverse events.

  8. Greater γ-tocopherol status during acute smoking abstinence with nicotine replacement therapy improved vascular endothelial function by decreasing 8-iso-15(S)-prostaglandin F2α.

    PubMed

    Mah, Eunice; Pei, Ruisong; Guo, Yi; Masterjohn, Christopher; Ballard, Kevin D; Taylor, Beth A; Taylor, Alan W; Traber, Maret G; Volek, Jeff S; Bruno, Richard S

    2015-04-01

    Nicotine replacement therapy (NRT) improves the long-term success rate of smoking cessation, but induces oxidative stress and inflammatory responses that may delay the restoration of vascular endothelial function (VEF). No studies have examined co-therapy of NRT-assisted smoking abstinence with γ-tocopherol (γ-T), a vitamin E form with antioxidant and anti-inflammatory activities, on improvements in VEF. In a randomized, double-blind, placebo-controlled study, healthy smokers (25 ± 1 y old; mean ± SEM) received NRT and abstained from smoking for 24 h with placebo (n = 12) or oral administration of γ-T-rich mixture of tocopherols (γ-TmT; n = 11) that provided 500 mg γ-T. Brachial artery flow-mediated dilation (FMD), and biomarkers of nitric oxide metabolism, antioxidant status, inflammation, and lipid peroxidation [8-iso-prostaglandin F2α stereoisomers (8-iso-15(R)-PGF2α and 8-iso-15(S)-PGF2α)] were measured prior to and after 24 h of smoking abstinence. Smoking abstinence with NRT regardless of γ-TmT similarly decreased urinary naphthol (P < 0.05) without affecting plasma cotinine. γ-TmT increased plasma γ-T by 4-times and the urinary metabolite of γ-T, γ-carboxyethyl-chromanol, by three times. Smoking abstinence with γ-TmT, but not smoking abstinence alone, increased FMD without affecting plasma nitrate/nitrite or the ratio of asymmetric dimethylarginine/arginine. Urinary 8-iso-15(S)-PGF2α decreased only in those receiving γ-TmT and was inversely correlated to FMD (R = -0.43, P < 0.05). Circulating markers of inflammation were unaffected by smoking abstinence or γ-TmT. Short-term NRT-assisted smoking abstinence with γ-TmT, but not NRT-assisted smoking abstinence alone, improved VEF by decreasing 8-iso-15(S)-PGF2α, a vasoconstrictor that was otherwise unaffected by NRT-assisted smoking abstinence. PMID:25361769

  9. Greater γ-tocopherol status during acute smoking abstinence with nicotine replacement therapy improved vascular endothelial function by decreasing 8-iso-15(S)-prostaglandin F2α

    PubMed Central

    Mah, Eunice; Pei, Ruisong; Guo, Yi; Masterjohn, Christopher; Ballard, Kevin D; Taylor, Beth A; Taylor, Alan W; Traber, Maret G; Volek, Jeff S

    2015-01-01

    Nicotine replacement therapy (NRT) improves the long-term success rate of smoking cessation, but induces oxidative stress and inflammatory responses that may delay the restoration of vascular endothelial function (VEF). No studies have examined co-therapy of NRT-assisted smoking abstinence with γ-tocopherol (γ-T), a vitamin E form with antioxidant and anti-inflammatory activities, on improvements in VEF. In a randomized, double-blind, placebo-controlled study, healthy smokers (25 ± 1 y old; mean ± SEM) received NRT and abstained from smoking for 24 h with placebo (n = 12) or oral administration of γ-T-rich mixture of tocopherols (γ-TmT; n = 11) that provided 500 mg γ-T. Brachial artery flow-mediated dilation (FMD), and biomarkers of nitric oxide metabolism, antioxidant status, inflammation, and lipid peroxidation [8-iso-prostaglandin F2α stereoisomers (8-iso-15(R)-PGF2α and 8-iso-15(S)-PGF2α)] were measured prior to and after 24 h of smoking abstinence. Smoking abstinence with NRT regardless of γ-TmT similarly decreased urinary naphthol (P < 0.05) without affecting plasma cotinine. γ-TmT increased plasma γ-T by 4-times and the urinary metabolite of γ-T, γ-carboxyethyl-chromanol, by three times. Smoking abstinence with γ-TmT, but not smoking abstinence alone, increased FMD without affecting plasma nitrate/nitrite or the ratio of asymmetric dimethylarginine/arginine. Urinary 8-iso-15(S)-PGF2α decreased only in those receiving γ-TmT and was inversely correlated to FMD (R = −0.43, P < 0.05). Circulating markers of inflammation were unaffected by smoking abstinence or γ-TmT. Short-term NRT-assisted smoking abstinence with γ-TmT, but not NRT-assisted smoking abstinence alone, improved VEF by decreasing 8-iso-15(S)-PGF2α, a vasoconstrictor that was otherwise unaffected by NRT-assisted smoking abstinence. PMID:25361769

  10. Greater γ-tocopherol status during acute smoking abstinence with nicotine replacement therapy improved vascular endothelial function by decreasing 8-iso-15(S)-prostaglandin F2α.

    PubMed

    Mah, Eunice; Pei, Ruisong; Guo, Yi; Masterjohn, Christopher; Ballard, Kevin D; Taylor, Beth A; Taylor, Alan W; Traber, Maret G; Volek, Jeff S; Bruno, Richard S

    2015-04-01

    Nicotine replacement therapy (NRT) improves the long-term success rate of smoking cessation, but induces oxidative stress and inflammatory responses that may delay the restoration of vascular endothelial function (VEF). No studies have examined co-therapy of NRT-assisted smoking abstinence with γ-tocopherol (γ-T), a vitamin E form with antioxidant and anti-inflammatory activities, on improvements in VEF. In a randomized, double-blind, placebo-controlled study, healthy smokers (25 ± 1 y old; mean ± SEM) received NRT and abstained from smoking for 24 h with placebo (n = 12) or oral administration of γ-T-rich mixture of tocopherols (γ-TmT; n = 11) that provided 500 mg γ-T. Brachial artery flow-mediated dilation (FMD), and biomarkers of nitric oxide metabolism, antioxidant status, inflammation, and lipid peroxidation [8-iso-prostaglandin F2α stereoisomers (8-iso-15(R)-PGF2α and 8-iso-15(S)-PGF2α)] were measured prior to and after 24 h of smoking abstinence. Smoking abstinence with NRT regardless of γ-TmT similarly decreased urinary naphthol (P < 0.05) without affecting plasma cotinine. γ-TmT increased plasma γ-T by 4-times and the urinary metabolite of γ-T, γ-carboxyethyl-chromanol, by three times. Smoking abstinence with γ-TmT, but not smoking abstinence alone, increased FMD without affecting plasma nitrate/nitrite or the ratio of asymmetric dimethylarginine/arginine. Urinary 8-iso-15(S)-PGF2α decreased only in those receiving γ-TmT and was inversely correlated to FMD (R = -0.43, P < 0.05). Circulating markers of inflammation were unaffected by smoking abstinence or γ-TmT. Short-term NRT-assisted smoking abstinence with γ-TmT, but not NRT-assisted smoking abstinence alone, improved VEF by decreasing 8-iso-15(S)-PGF2α, a vasoconstrictor that was otherwise unaffected by NRT-assisted smoking abstinence.

  11. A pilot study of prognostic value of non-invasive cardiac parameters for major adverse cardiac events in patients with acute coronary syndrome treated with percutaneous coronary intervention

    PubMed Central

    Yuan, Min-Jie; Pan, Ye-Sheng; Hu, Wei-Guo; Lu, Zhi-Gang; Zhang, Qing-Yong; Huang, Dong; Huang, Xiao-Li; Wei, Meng; Li, Jing-Bo

    2015-01-01

    The objective of this study was to determine the combination of left ventricular ejection fraction (LVEF) and individual electrocardiographic parameters related to abnormal depolarization/repolarization or baroreceptor sensitivity that had the best predictive value for major adverse cardiac events (MACE) in patients with acute coronary syndrome (ACS). Patients with ACS who underwent coronary angiography and percutaneous coronary intervention (PCI) were included in this prospective study. Ventricular late potential (VLP), heart rate turbulence (HRT), heart rate variability (HRV), and T wave alternans (TWA) parameters were measured using 24 h Holter monitoring 2-4 weeks after onset of ACS. Initial and follow-up LVEF was measured by ultrasound. Patients were followed for at least 6 months to record the occurrence of MACE. Models using combinations of the individual independent prognostic factors found by multivariate analysis were then constructed to use for estimation of risk of MACE. In multivariate analysis, VLP measured as QRS duration, HRV measured as standard deviation of normal RR intervals, and followup LVEF, but none of the other parameters studied, were independent risk factors for MACE. Areas under ROC curve (AUCs) for combinations of 2 or all 3 factors ranged from 0.73 to 0.76. Combinations of any of the three independent risk factors for MACE in ACS patients with PCI improved prediction and, because these risk factors were obtained non-invasively, may have future clinical usefulness. PMID:26885226

  12. The Modification Effect of Influenza Vaccine on Prognostic Indicators for Cardiovascular Events after Acute Coronary Syndrome: Observations from an Influenza Vaccination Trial.

    PubMed

    Sribhutorn, Apirak; Phrommintikul, Arintaya; Wongcharoen, Wanwarang; Chaikledkaew, Usa; Eakanunkul, Suntara; Sukonthasarn, Apichard

    2016-01-01

    Introduction. The prognosis of acute coronary syndrome (ACS) patients has been improved with several treatments such as antithrombotics, beta-blockers, and angiotensin-converting enzyme inhibitors (ACEI) as well as coronary revascularization. Influenza vaccination has been shown to reduce adverse outcomes in ACS, but no information exists regarding the interaction of other treatments. Methods. This study included 439 ACS patients from Phrommintikul et al. A single dose of inactivated influenza vaccine was given by intramuscular injection in the vaccination group. The cardiovascular outcomes were described as major cardiovascular events (MACEs) which included mortality, hospitalization due to ACS, and hospitalization due to heart failure (HF). The stratified and multivariable Cox's regression analysis was performed. Results. The stratified Cox's analysis by influenza vaccination for each cardiovascular outcome and discrimination of hazard ratios showed that beta-blockers had an interaction with influenza vaccination. Moreover, the multivariable hazard ratios disclosed that influenza vaccine is associated with a significant reduction of hospitalization due to HF in patients who received beta-blockers (HR = 0.05, 95% CI = 0.004-0.71, P = 0.027), after being adjusted for prognostic indicators (sex, dyslipidemia, serum creatinine, and left ventricular ejection fraction). Conclusions. The influenza vaccine was shown to significantly modify the effect of beta-blockers in ACS patients and to reduce the hospitalization due to HF. However, further study of a larger population and benefits to HF patients should be investigated. PMID:27200206

  13. Vascular tumors and malformations in children, Introduction.

    PubMed

    Maguiness, Sheilagh M

    2016-03-01

    Over the past decade, I have been amazed at the growth in the field of vascular anomalies. The recognition of vascular birthmarks as a defined area of medicine is a relatively recent event. The International Society for the Study of Vascular Anomalies (ISSVA) was founded by Drs John Mulliken and Anthony Young in the late 1970s. Mulliken and Glowacki's sentinel 1982 paper on the biologic classification of vascular anomalies further established the field, by providing clarity of nomenclature and unifying concepts that had previously been lacking. PMID:27607317

  14. Cardiovascular risk factors for acute stroke: Risk profiles in the different subtypes of ischemic stroke.

    PubMed

    Arboix, Adrià

    2015-05-16

    Timely diagnosis and control of cardiovascular risk factors is a priority objective for adequate primary and secondary prevention of acute stroke. Hypertension, atrial fibrillation and diabetes mellitus are the most common risk factors for acute cerebrovascular events, although novel risk factors, such as sleep-disordered breathing, inflammatory markers or carotid intima-media thickness have been identified. However, the cardiovascular risk factors profile differs according to the different subtypes of ischemic stroke. Atrial fibrillation and ischemic heart disease are more frequent in patients with cardioembolic infarction, hypertension and diabetes in patients with lacunar stroke, and vascular peripheral disease, hypertension, diabetes, previous transient ischemic attack and chronic obstructive pulmonary disease in patients with atherothrombotic infarction. This review aims to present updated data on risk factors for acute ischemic stroke as well as to describe the usefulness of new and emerging vascular risk factors in stroke patients.

  15. Cardiovascular risk factors for acute stroke: Risk profiles in the different subtypes of ischemic stroke.

    PubMed

    Arboix, Adrià

    2015-05-16

    Timely diagnosis and control of cardiovascular risk factors is a priority objective for adequate primary and secondary prevention of acute stroke. Hypertension, atrial fibrillation and diabetes mellitus are the most common risk factors for acute cerebrovascular events, although novel risk factors, such as sleep-disordered breathing, inflammatory markers or carotid intima-media thickness have been identified. However, the cardiovascular risk factors profile differs according to the different subtypes of ischemic stroke. Atrial fibrillation and ischemic heart disease are more frequent in patients with cardioembolic infarction, hypertension and diabetes in patients with lacunar stroke, and vascular peripheral disease, hypertension, diabetes, previous transient ischemic attack and chronic obstructive pulmonary disease in patients with atherothrombotic infarction. This review aims to present updated data on risk factors for acute ischemic stroke as well as to describe the usefulness of new and emerging vascular risk factors in stroke patients. PMID:25984516

  16. Cardiovascular risk factors for acute stroke: Risk profiles in the different subtypes of ischemic stroke

    PubMed Central

    Arboix, Adrià

    2015-01-01

    Timely diagnosis and control of cardiovascular risk factors is a priority objective for adequate primary and secondary prevention of acute stroke. Hypertension, atrial fibrillation and diabetes mellitus are the most common risk factors for acute cerebrovascular events, although novel risk factors, such as sleep-disordered breathing, inflammatory markers or carotid intima-media thickness have been identified. However, the cardiovascular risk factors profile differs according to the different subtypes of ischemic stroke. Atrial fibrillation and ischemic heart disease are more frequent in patients with cardioembolic infarction, hypertension and diabetes in patients with lacunar stroke, and vascular peripheral disease, hypertension, diabetes, previous transient ischemic attack and chronic obstructive pulmonary disease in patients with atherothrombotic infarction. This review aims to present updated data on risk factors for acute ischemic stroke as well as to describe the usefulness of new and emerging vascular risk factors in stroke patients. PMID:25984516

  17. Effects of Rosuvastatin and MiR-126 on Myocardial Injury Induced by Acute Myocardial Infarction in Rats: Role of Vascular Endothelial Growth Factor A (VEGF-A)

    PubMed Central

    Fei, Ling; Zhang, Jun; Niu, Heping; Yuan, Chen; Ma, Xiaoli

    2016-01-01

    Background The present study investigated the effects of VEGF-A targeted by miR-126 on myocardial injury after acute myocardial infarction (AMI) in rats, along with the contributions of rosuvastatin to the synergic effect. Material/Methods SD rats were obtained to construct AMI models by ligating their left anterior descending coronary arteries (LAD). We conducted echocardiography to check the 6 involved indexes: left ventricular ejection fractions (LVEF), fractional shortening (FS), left ventricular end-systolic volume (LVV), left ventricular end-diastolic volume (LVVd), cardiac output (CO), and heart rate (HR). Moreover, antibody sandwich enzyme-linked immunosorbent assay was carried out to determine MI markers: creatine kinase (CK), CK Isoenzyme (CK-MB), and Troponin I (cTn I). Dual-Luciferase Reporter Assay was performed to confirm the targeting of miR-126 and VEGF-A. MTT assay provided insight into the proliferation of myocardial fibroblasts. Finally, RT-RCR and Western blot were used for the detection of miR-126 and VEGF-A expressions in vivo and in vitro. Results Luciferase activity assay showed that miR-126 transfection significantly decreased the relative luciferase activity in HEK293T cells when it was bound to normal 3′ UTR of VEGF-A (P<0.05). In comparison to the control group, rats in the AMI model group had significantly lower LVEF, FS, and CO, and substantially higher LVVs, LVVd, HR, CK/U, CK-MB/U, and cTn-1/U (all P<0.05). Down-regulated miR-126 and up-regulated VEGF-A were also observed in MI models (P<0.05). Conclusions miR-126 and rosuvastatin have protective effects on AMI risk, and VEGF-A antagonizes effects on AMI is imposed by. PMID:27376405

  18. Usefulness of Beta2-Microglobulin as a Predictor of All-Cause and Nonculprit Lesion-Related Cardiovascular Events in Acute Coronary Syndromes (from the PROSPECT Study).

    PubMed

    Möckel, Martin; Muller, Reinhold; Searle, Julia; Slagman, Anna; De Bruyne, Bernard; Serruys, Patrick; Weisz, Giora; Xu, Ke; Holert, Fabian; Müller, Christian; Maehara, Akiko; Stone, Gregg W

    2015-10-01

    In the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study, plaque burden, plaque composition, and minimal luminal area were associated with an increased risk of adverse cardiovascular events arising from untreated atherosclerotic lesions (vulnerable plaques) in patients with acute coronary syndromes (ACS). We sought to evaluate the utility of biomarker profiling and clinical risk factors to predict 3-year all-cause and nonculprit lesion-related major adverse cardiac events (MACEs). Of 697 patients who underwent successful percutaneous coronary intervention (PCI) for ACS, an array of 28 baseline biomarkers was analyzed. Median follow-up was 3.4 years. Beta2-microglobulin displayed the strongest predictive power of all variables assessed for all-cause and nonculprit lesion-related MACE. In a classification and regression tree analysis, patients with beta2-microglobulin >1.92 mg/L had an estimated 28.7% 3-year incidence of all-cause MACE; C-peptide <1.32 ng/ml was associated with a further increase in MACE to 51.2%. In a classification and regression tree analysis for untreated nonculprit lesion-related MACE, beta2-microglobulin >1.92 mg/L identified a cohort with a 3-year rate of 18.5%, and C-peptide <2.22 ng/ml was associated with a further increase to 25.5%. By multivariable analysis, beta2-microglobulin was the strongest predictor of all-cause and nonculprit MACE during follow-up. High-density lipoprotein (HDL), transferrin, and history of angina pectoris were also independent predictors of all-cause MACE, and HDL was an independent predictor of nonculprit MACE. In conclusion, in the PROSPECT study, beta2-microglobulin strongly predicted all-cause and nonculprit lesion-related MACE within 3 years after PCI in ACS. C-peptide and HDL provided further risk stratification to identify angiographically mild nonculprit lesions prone to future MACE.

  19. Usefulness of Beta2-Microglobulin as a Predictor of All-Cause and Nonculprit Lesion-Related Cardiovascular Events in Acute Coronary Syndromes (from the PROSPECT Study).

    PubMed

    Möckel, Martin; Muller, Reinhold; Searle, Julia; Slagman, Anna; De Bruyne, Bernard; Serruys, Patrick; Weisz, Giora; Xu, Ke; Holert, Fabian; Müller, Christian; Maehara, Akiko; Stone, Gregg W

    2015-10-01

    In the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study, plaque burden, plaque composition, and minimal luminal area were associated with an increased risk of adverse cardiovascular events arising from untreated atherosclerotic lesions (vulnerable plaques) in patients with acute coronary syndromes (ACS). We sought to evaluate the utility of biomarker profiling and clinical risk factors to predict 3-year all-cause and nonculprit lesion-related major adverse cardiac events (MACEs). Of 697 patients who underwent successful percutaneous coronary intervention (PCI) for ACS, an array of 28 baseline biomarkers was analyzed. Median follow-up was 3.4 years. Beta2-microglobulin displayed the strongest predictive power of all variables assessed for all-cause and nonculprit lesion-related MACE. In a classification and regression tree analysis, patients with beta2-microglobulin >1.92 mg/L had an estimated 28.7% 3-year incidence of all-cause MACE; C-peptide <1.32 ng/ml was associated with a further increase in MACE to 51.2%. In a classification and regression tree analysis for untreated nonculprit lesion-related MACE, beta2-microglobulin >1.92 mg/L identified a cohort with a 3-year rate of 18.5%, and C-peptide <2.22 ng/ml was associated with a further increase to 25.5%. By multivariable analysis, beta2-microglobulin was the strongest predictor of all-cause and nonculprit MACE during follow-up. High-density lipoprotein (HDL), transferrin, and history of angina pectoris were also independent predictors of all-cause MACE, and HDL was an independent predictor of nonculprit MACE. In conclusion, in the PROSPECT study, beta2-microglobulin strongly predicted all-cause and nonculprit lesion-related MACE within 3 years after PCI in ACS. C-peptide and HDL provided further risk stratification to identify angiographically mild nonculprit lesions prone to future MACE. PMID:26254706

  20. MicroRNAs Regulate Vascular Medial Calcification.

    PubMed

    Leopold, Jane A

    2014-01-01

    Vascular calcification is highly prevalent in patients with coronary artery disease and, when present, is associated with major adverse cardiovascular events, including an increased risk of cardiovascular mortality. The pathogenesis of vascular calcification is complex and is now recognized to recapitulate skeletal bone formation. Vascular smooth muscle cells (SMC) play an integral role in this process by undergoing transdifferentiation to osteoblast-like cells, elaborating calcifying matrix vesicles and secreting factors that diminish the activity of osteoclast-like cells with mineral resorbing capacity. Recent advances have identified microRNAs (miRs) as key regulators of this process by directing the complex genetic reprogramming of SMCs and the functional responses of other relevant cell types relevant for vascular calcification. This review will detail SMC and bone biology as it relates to vascular calcification and relate what is known to date regarding the regulatory role of miRs in SMC-mediated vascular calcification.

  1. Abdominal Distension and Vascular Collapse.

    PubMed

    Cosentino, Gina; Uwaifo, Gabriel I

    2016-04-01

    We present the case of a 43-year-old gentleman who presented to the emergency room with acute abdominal distension, confusion and vascular collapse. The emergent radiologic imaging obtained showed massive bilateral adrenal enlargement, but despite the initial clinical suspicion of possible overwhelming sepsis and/or massive abdominal/intralesional hemorrhage, lab tests based obtained rapidly confirmed the diagnosis of acute Addisonian crisis which responded dramatically to adrenocorticoid hormone replacement therapy and aggressive fluid resuscitation. The patient's established history of metastatic lung cancer confirmed this as a case of metastatic massive bilateral adrenal metastases with an initial presentation of acute adrenal insufficiency which is uncommon in the setting of metastatic carcinomatosis but more typically associated with lymphomas. Recognition of this clinical possibility is vital to enable rapid diagnosis and consequent life saving therapy. PMID:27328473

  2. 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.

  3. 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. PMID:21809965

  4. (n-3) Fatty acid content of red blood cells does not predict risk of future cardiovascular events following an acute coronary syndrome.

    PubMed

    Aarsetoey, Hildegunn; Pönitz, Volker; Grundt, Heidi; Staines, Harry; Harris, William S; Nilsen, Dennis W T

    2009-03-01

    A reduced risk of fatal coronary artery disease has been associated with a high intake of (n-3) fatty acids (FA) and a direct cardioprotective effect by their incorporation into myocardial cells has been suggested. Based on these observations, the omega-3 index (eicosapentaenoic acid + docosahexaenoic acid in cell membranes of RBC expressed as percent of total FA) has been suggested as a new risk marker for cardiac death. In this study, our aim was to evaluate the omega-3 index as a prognostic risk marker following hospitalization with an acute coronary syndrome (ACS). The omega-3 index was measured at admission in 460 patients with an ACS as defined by Troponin-T (TnT) > or = 0.02 microg/L. During a 2-y follow-up, recurrent myocardial infarctions (MI) (defined as TnT > 0.05 microg/L with a typical MI presentation) and cardiac and all-cause mortality were registered. Cox regression analyses were used to relate the risk of new events to the quartiles of the omega-3 index at inclusion. After correction for age, sex, previous heart disease, hypertension, diabetes, smoking, high-sensitivity C-reactive protein, brain natriuretic peptide, creatinine, total cholesterol, HDL-cholesterol, triacylglycerol, homocysteine, BMI, and medication, there was no significant reduction in risk for all-cause mortality, cardiac death, or MI with increasing values of the index. In conclusion, we could not confirm the omega-3 index as a useful prognostic risk marker following an ACS. PMID:19158216

  5. Improved Early Event-Free Survival With Imatinib in Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia: A Children's Oncology Group Study

    PubMed Central

    Schultz, Kirk R.; Bowman, W. Paul; Aledo, Alexander; Slayton, William B.; Sather, Harland; Devidas, Meenakshi; Wang, Chenguang; Davies, Stella M.; Gaynon, Paul S.; Trigg, Michael; Rutledge, Robert; Burden, Laura; Jorstad, Dean; Carroll, Andrew; Heerema, Nyla A.; Winick, Naomi; Borowitz, Michael J.; Hunger, Stephen P.; Carroll, William L.; Camitta, Bruce

    2009-01-01

    Purpose Imatinib mesylate is a targeted agent that may be used against Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL), one of the highest risk pediatric ALL groups. Patients and Methods We evaluated whether imatinib (340 mg/m2/d) with an intensive chemotherapy regimen improved outcome in children ages 1 to 21 years with Ph+ ALL (N = 92) and compared toxicities to Ph− ALL patients (N = 65) given the same chemotherapy without imatinib. Exposure to imatinib was increased progressively in five patient cohorts that received imatinib from 42 (cohort 1; n = 7) to 280 continuous days (cohort 5; n = 50) before maintenance therapy. Patients with human leukocyte antigen (HLA) –identical sibling donors underwent blood and marrow transplantation (BMT) with imatinib given for 6 months following BMT. Results Continuous imatinib exposure improved outcome in cohort 5 patients with a 3-year event-free survival (EFS) of 80% ± 11% (95% CI, 64% to 90%), more than twice historical controls (35% ± 4%; P < .0001). Three-year EFS was similar for patients in cohort 5 treated with chemotherapy plus imatinib (88% ± 11%; 95% CI, 66% to 96%) or sibling donor BMT (57% ± 22%; 95% CI, 30.4% to 76.1%). There were no significant toxicities associated with adding imatinib to intensive chemotherapy. The higher imatinib dosing in cohort 5 appears to improve survival by having an impact on the outcome of children with a higher burden of minimal residual disease after induction. Conclusion Imatinib plus intensive chemotherapy improved 3-year EFS in children and adolescents with Ph+ ALL, with no appreciable increase in toxicity. BMT plus imatinib offered no advantage over BMT alone. Additional follow-up is required to determine the impact of this treatment on long-term EFS and determine whether chemotherapy plus imatinib can replace BMT. PMID:19805687

  6. Resting heart rate associates with one-year risk of major adverse cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention

    PubMed Central

    Wang, Shao-Li; Wang, Cheng-Long; Wang, Pei-Li; Xu, Hao; Du, Jian-Peng; Zhang, Da-Wu; Gao, Zhu-Ye; Zhang, Lei; Fu, Chang-Geng; Chen, Ke-Ji

    2015-01-01

    The study was to access the association between resting heart rate (RHR) and one-year risk of major adverse cardiovascular events (MACE) in acute coronary syndrome (ACS) patients after percutaneous coronary intervention (PCI). Patients with ACS after PCI (n = 808) were prospectively followed-up for MACE. RHR was obtained from electrocardiogram. MACE was defined as a composite of cardiac death, nonfatal recurrent myocardial infarction, ischemic-driven revascularization, and ischemic stroke. The association between RHR and one-year risk of MACE was assessed using Cox proportional hazards regression model. Compared with patients with RHR >76 bpm, the adjusted hazard ratio (AHR) was 0.51 (95% confidence intervals [CI]: 0.23–1.14; P = 0.100) for patients with RHR < 61 bpm, and 0.44 (95%CI: 0.23–0.85; P = 0.014) for those with RHR 61–76 bpm. For patients with RHR ≥ 61 bpm, an increase of 10 bpm in RHR was associated with an increase by 38.0% in the risk of MACE (AHR: 1.38; 95% CI: 1.04–1.83; P = 0.026). ACS patients after PCI with RHR >76 bpm were at higher risk of MACE during one-year follow-up compared with patients with RHR 61–76 bpm. An elevated RHR ≥ 61 bpm was associated with increased risk of one-year MACE in ACS patients. PMID:26585407

  7. The evolution of dual antiplatelet therapy in the setting of acute coronary syndrome: ticagrelor versus clopidogrel.

    PubMed

    Amico, Frank; Amico, Angela; Mazzoni, Jennifer; Moshiyakhov, Mark; Tamparo, William

    2016-01-01

    Review of: Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Eng J Med 2009; 361(11): 1045-1057. For acute coronary syndrome (ACS), a dual antiplatelet regimen comprised of treatment with aspirin and either P2Y12 adenosine diphosphate receptor antagonists, clopidogrel, prasugrel or ticagrelor is usually employed. This article compares clopidogrel with ticagrelor for the prevention of vascular events and death in broad population of ACS patients ranging from UA, NSTEMI to STEMI, utilizing planned strategies of medical or invasive treatment strategy. PMID:26560350

  8. Vascular ring diagnosis following respiratory arrest

    PubMed Central

    Robson, Evie Alexandra; Scott, Alison; Chetcuti, Philip; Crabbe, David

    2014-01-01

    Vascular rings can present with non-specific respiratory and/or oesophageal symptoms. Early diagnosis requires a high index of suspicion. This case report describes an uncommon acute presentation of a vascular ring. We report a thriving 14-month-old child with a long history of recurrent wheeze and ‘noisy breathing’. He presented acutely with food bolus impaction in the oesophagus which led to a respiratory arrest. Oesophagoscopy and bronchoscopy suggested vascular ring anomaly. A contrast-enhanced CT scan demonstrated a right-sided aortic arch with left ligamentum arteriosum encircling the oesophagus and airway. The ligament was ligated and divided. At follow-up 6 months later, the infant had mild persistent stridor but was otherwise well. PMID:24895385

  9. Pentoxifylline for vascular health: a brief review of the literature.

    PubMed

    McCarty, Mark F; O'Keefe, James H; DiNicolantonio, James J

    2016-01-01

    Pentoxifylline is a methylxanthine derivative that has been used for several decades in the symptomatic management of intermittent claudication. For reasons that remain fairly obscure, this drug benefits blood rheology in a number of complementary ways: decreasing blood and plasma viscosity, lowering plasma fibrinogen while promoting fibrinolysis, and improving blood filterability by enhancing erythrocyte distensibility and lessening neutrophil activation. Anti-inflammatory effects on neutrophils and macrophage/monocytes-some of them attributable to pentoxifylline metabolites-appear to play a mediating role in this regard. Although clinical trials with pentoxifylline have often been too small in size to reach statistically significant findings regarding impacts on hard end points, a review of the existing literature suggests that pentoxifylline may have potential for slowing the progression of atherosclerosis, stabilising plaque, reducing risk for vascular events, improving the outcome of vascular events, dampening the systemic inflammatory response following cardiopulmonary bypass, providing symptomatic benefit in angina and intermittent claudication, enhancing cerebral blood flow in patients with cerebrovascular disease while slowing progression of vascular dementia, improving prognosis in congestive heart failure, and aiding diabetes control. This safe and usually well-tolerated drug works in ways quite distinct from other drugs more commonly used for cardiovascular protection, and hence may confer complementary benefit when used in conjunction with them. Major clinical trials of adequate statistical power are now needed to confirm the scope of benefits that pentoxifylline can confer; studies evaluating hard end points in acute coronary syndrome, stroke/transient ischaemic attack and systolic heart failure might be particularly valuable. PMID:26870389

  10. Pentoxifylline for vascular health: a brief review of the literature

    PubMed Central

    McCarty, Mark F; O'Keefe, James H; DiNicolantonio, James J

    2016-01-01

    Pentoxifylline is a methylxanthine derivative that has been used for several decades in the symptomatic management of intermittent claudication. For reasons that remain fairly obscure, this drug benefits blood rheology in a number of complementary ways: decreasing blood and plasma viscosity, lowering plasma fibrinogen while promoting fibrinolysis, and improving blood filterability by enhancing erythrocyte distensibility and lessening neutrophil activation. Anti-inflammatory effects on neutrophils and macrophage/monocytes—some of them attributable to pentoxifylline metabolites—appear to play a mediating role in this regard. Although clinical trials with pentoxifylline have often been too small in size to reach statistically significant findings regarding impacts on hard end points, a review of the existing literature suggests that pentoxifylline may have potential for slowing the progression of atherosclerosis, stabilising plaque, reducing risk for vascular events, improving the outcome of vascular events, dampening the systemic inflammatory response following cardiopulmonary bypass, providing symptomatic benefit in angina and intermittent claudication, enhancing cerebral blood flow in patients with cerebrovascular disease while slowing progression of vascular dementia, improving prognosis in congestive heart failure, and aiding diabetes control. This safe and usually well-tolerated drug works in ways quite distinct from other drugs more commonly used for cardiovascular protection, and hence may confer complementary benefit when used in conjunction with them. Major clinical trials of adequate statistical power are now needed to confirm the scope of benefits that pentoxifylline can confer; studies evaluating hard end points in acute coronary syndrome, stroke/transient ischaemic attack and systolic heart failure might be particularly valuable. PMID:26870389

  11. A systematic review of acute pancreatitis as an adverse event of type 2 diabetes drugs: from hard facts to a balanced position.

    PubMed

    Giorda, C B; Nada, E; Tartaglino, B; Marafetti, L; Gnavi, R

    2014-11-01

    The question whether antidiabetes drugs can cause acute pancreatitis dates back to the 1970s. Recently, old concerns have re-emerged following claims that use of incretins, a new class of drugs for type 2 diabetes, might increase the relative risk of acute pancreatitis up to 30-fold. Given that diabetes is per se a potent risk factor for acute pancreatitis and that drug-related acute pancreatitis is rare and difficult to diagnose, we searched the medical databases for information linking acute pancreatitis and type 2 diabetes drugs. Among the biguanides, both phenformin and metformin (the latter in patients with renal insufficiency) have been cited in case reports as a potential cause of acute pancreatitis. Sulphonylureas, as both entire class and single compound (glibenclamide), have also been found in cohort studies to increase its risk. No direct link was found between pancreatic damage and therapy with metaglinide, acarbose, pramlintide or SGLT-2 inhibitors. In animal models, thiazolinediones have demonstrated proprieties to attenuate pancreatic damage, opening perspectives for their use in treating acute pancreatitis in humans. Several case reports and the US Food and Drug Administration pharmacovigilance database indicate an association between acute pancreatitis and incretins, dipeptidyl peptidase-4 (DPP-4) inhibitors, and GLP-1 receptor agonists. To date, however, a clear-cut odds ratio for this association has been reported in only one of eight pharmacoepidemiological studies. Finally, none of the intervention trials investigating these compounds, including two large randomized controlled trials with cardiovascular endpoints, confirmed the purportedly increased risk of acute pancreatitis with incretin use.

  12. Clinical characteristics, management and 1-year outcomes of patients with acute coronary syndrome in Iran: the Iranian Project for Assessment of Coronary Events 2 (IPACE2)

    PubMed Central

    Kassaian, Seyed Ebrahim; Masoudkabir, Farzad; Sezavar, Hashem; Mohammadi, Mohammad; Pourmoghaddas, Ali; Kojouri, Javad; Ghaffari, Samad; Sanaati, Hamidreza; Alaeddini, Farshid; Pourmirza, Bahin; Mir, Elham

    2015-01-01

    Objectives To assess contemporary data on characteristics, management and 1-year postdischarge outcomes in Iranian patients hospitalised with acute coronary syndrome (ACS). Setting 11 tertiary care hospitals in 5 major cities in the Islamic Republic of Iran. Participants Patients aged ≥20 and ≤80 years discharged alive with confirmed diagnosis of ACS including ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) and high-risk unstable angina (HR-UA). Primary and secondary outcome measures Patients were followed up regarding the use of medications and the end points of the study at 1 month and 1 year after discharge. The primary end point of the study was 1-year postdischarge major adverse cardiac and cerebrovascular events (MACCEs), defined as mortality (cardiac and non-cardiac), ACS and cerebrovascular attack (stroke and/or transient ischaemic attack). The secondary end points were hospital admission because of congestive heart failure, revascularisation by coronary artery bypass grafting surgery or percutaneous coronary intervention (PCI), and major and minor bleeds. Results A total of 1799 patients (25.7% STEMI and 74.3% HR-UA/NSTEMI) discharged alive with confirmed diagnosis of ACS were included in the final analysis. During hospitalisation, the majority of the patients received aspirin (98.6%), clopidogrel (91.8%), anticoagulants (93.4%), statins (94.3%) and β-blockers (89.3%). Reperfusion therapy was performed in 62.6% of patients with STEMI (46.3% thrombolytic therapy and 17.3% primary PCI). The mean door-to-balloon and door-to-needle times were 82.9 and 45.6 min, respectively. In our study, 64.7% and 79.5% of the patients in HR-UA/NSTEMI and STEMI groups, respectively, underwent coronary angiography. During the 12 months after discharge, MACCEs occurred in 15.0% of all patients. Conclusions Our study showed that the composition of Iranian patients with ACS regarding the type of ACS is similar to that in developed European

  13. Red blood cell distribution width independently predicts medium-term mortality and major adverse cardiac events after an acute coronary syndrome

    PubMed Central

    Turcato, Gianni; Serafini, Valentina; Dilda, Alice; Bovo, Chiara; Caruso, Beatrice; Ricci, Giorgio

    2016-01-01

    Background The value of red blood cell distribution width (RDW), a simple and inexpensive measure of anisocytosis, has been associated with the outcome of many human chronic disorders. Therefore, this retrospective study was aimed to investigate whether RDW may be associated with medium-term mortality and major adverse cardiac events (MACE) after an acute coronary syndrome (ACS). Methods A total number of 979 patients diagnosed with ACS were enrolled from June 2014 to November 2014, and followed-up until June 2015. Results The RDW value in patients with 3-month MACE and in those who died was significantly higher than that of patients without 3-month MACE (13.3% vs. 14.0%; P<0.001) and those who were still alive at the end of follow-up (13.4% vs. 14.4%; P<0.001). In univariate analysis, RDW was found to be associated with 3-month MACE [odds ratio (OR), 1.70; 95% CI, 1.44–2.00, P<0.001]. In multivariate analysis, RDW remained independently associated with 3-month MACE (adjusted OR, 1.36; 95% CI, 1.19–1.55; P<0.001) and death (adjusted OR, 1.34; 95% CI, 1.05–1.71; P=0.020). The accuracy of RDW for predicting 3-month MACE was 0.67 (95% CI, 0.66–0.72; P<0.001). The most efficient discriminatory RDW value was 14.8%, which was associated with 3.8 (95% CI, 2.6–5.7; P<0.001) higher risk of 3-month MACE. Patients with RDW >14.8% exhibited a significantly short survival than those with RDW ≤14.8% (331 vs. 465 days; P<0.001). Conclusions The results of this study confirm that RDW may be a valuable, easy and inexpensive parameter for stratifying the medium-term risk in patients with ACS. PMID:27500155

  14. 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.

  15. Beneficial effects through aggressive coronary screening for type 2 diabetes patients with advanced vascular complications.

    PubMed

    Tsujimoto, Tetsuro; Sugiyama, Takehiro; Yamamoto-Honda, Ritsuko; Kishimoto, Miyako; Noto, Hiroshi; Morooka, Miyako; Kubota, Kazuo; Kamimura, Munehiro; Hara, Hisao; Kajio, Hiroshi; Kakei, Masafumi; Noda, Mitsuhiko

    2016-08-01

    Glycemic control alone does not reduce cardiovascular events in patients with type 2 diabetes (T2D), and routine screening of all T2D patients for asymptomatic coronary artery disease (CAD) is not effective for preventing acute cardiac events. We examined the effectiveness of an aggressive screening protocol for asymptomatic CAD in T2D patients with advanced vascular complications.We designed a 3-year cohort study investigating the effectiveness of the aggressive coronary screening for T2D patients with advanced vascular complications and no known coronary events using propensity score adjusted analysis at a national center in Japan. Eligibility criteria included T2D without known coronary events and with any 1 of the following 4 complications: advanced diabetic retinopathy, advanced chronic kidney disease, peripheral artery disease, or cerebrovascular disease. In the aggressive screening group (n = 122), all patients received stress single photon emission computed tomography and those exhibiting myocardial perfusion abnormalities underwent coronary angiography. In the conventional screening group (n = 108), patients were examined for CAD at the discretion of their medical providers. Primary endpoint was composite outcome of cardiovascular death and nonfatal cardiovascular events.Asymptomatic CAD with ≥70% stenosis was detected in 39.3% of patients completing aggressive screening. The proportions achieving revascularization and receiving intensive medical therapy within 90 days after the screening were significantly higher in the aggressive screening group than in the conventional screening group [19.7% vs 0% (P < 0.001) and 48.4% vs 9.3% (P < 0.001), respectively]. The cumulative rate of primary composite outcome was significantly lower in the aggressive screening group according to a propensity score adjusted Cox proportional hazards model (hazard ratio, 0.35; 95% confidence interval, 0.12-0.96; P = 0.04).Aggressive coronary screening for T2D patients

  16. Plant Vascular Biology 2013: vascular trafficking.

    PubMed

    Ursache, Robertas; Heo, Jung-Ok; Helariutta, Ykä

    2014-04-01

    About 200 researchers from around the world attended the Third International Conference on Plant Vascular Biology (PVB 2013) held in July 2013 at the Rantapuisto Conference Center, in Helsinki, Finland (http://www.pvb2013.org). The plant vascular system, which connects every organ in the mature plant, continues to attract the interest of researchers representing a wide range of disciplines, including development, physiology, systems biology, and computational biology. At the meeting, participants discussed the latest research advances in vascular development, long- and short-distance vascular transport and long-distance signalling in plant defence, in addition to providing a context for how these studies intersect with each other. The meeting provided an opportunity for researchers working across a broad range of fields to share ideas and to discuss future directions in the expanding field of vascular biology. In this report, the latest advances in understanding the mechanism of vascular trafficking presented at the meeting have been summarized.

  17. Mechanisms and Clinical Consequences of Vascular Calcification

    PubMed Central

    Zhu, Dongxing; Mackenzie, Neil C. W.; Farquharson, Colin; MacRae, Vicky E.

    2012-01-01

    Vascular calcification has severe clinical consequences and is considered an accurate predictor of future adverse cardiovascular events, including myocardial infarction and stroke. Previously vascular calcification was thought to be a passive process which involved the deposition of calcium and phosphate in arteries and cardiac valves. However, recent studies have shown that vascular calcification is a highly regulated, cell-mediated process similar to bone formation. In this article, we outline the current understanding of key mechanisms governing vascular calcification and highlight the clinical consequences. By understanding better the molecular pathways and genetic circuitry responsible for the pathological mineralization process novel drug targets may be identified and exploited to combat and reduce the detrimental effects of vascular calcification on human health. PMID:22888324

  18. Endostatin induces acute endothelial nitric oxide and prostacyclin release

    SciTech Connect

    Li Chunying; Harris, M. Brennan; Venema, Virginia J.; Venema, Richard C. . E-mail: rvenema@mcg.edu

    2005-04-15

    Chronic exposure to endostatin (ES) blocks endothelial cell (EC) proliferation, and migration and induces EC apoptosis thereby inhibiting angiogenesis. Nitric oxide (NO) and prostacyclin (PGI{sub 2}), in contrast, play important roles in promoting angiogenesis. In this study, we examined the acute effects of ES on endothelial NO and PGI{sub 2} production. Unexpectedly, a cGMP reporter cell assay showed that ES-induced acute endothelial NO release in cultured bovine aortic endothelial cells (BAECs). Enzyme immunoassay showed that ES also induced an acute increase in PGI{sub 2} production in BAECs. These results were confirmed by ex vivo vascular ring studies that showed vascular relaxation in response to ES. Immunoblot analysis showed that ES stimulated acute phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser116, Ser617, Ser635, and Ser1179, and dephosphorylation at Thr497 in BAECs, events associated with eNOS activation. Short-term exposure of EC to ES, therefore, unlike long-term exposure which is anti-angiogenic, may be pro-angiogenic.

  19. 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.

  20. Vascular elastic photoacoustic tomography in humans

    NASA Astrophysics Data System (ADS)

    Hai, Pengfei; Zhou, Yong; Liang, Jinyang; Li, Chiye; Wang, Lihong V.

    2016-03-01

    Quantification of vascular elasticity can help detect thrombosis and prevent life-threatening conditions such as acute myocardial infarction or stroke. Here, we propose vascular elastic photoacoustic tomography (VE-PAT) to measure vascular elasticity in humans. VE-PAT was developed by incorporating a linear-array-based photoacoustic computed tomography system with a customized compression stage. By measuring the deformation of blood vessels under uniaxial loading, VE-PAT was able to quantify the vascular compliance. We first demonstrated the feasibility of VE-PAT in blood vessel phantoms. In large vessel phantoms, VE-PAT detected a decrease in vascular compliance due to simulated thrombosis, which was validated by a standard compression test. In small blood vessel phantoms embedded 3 mm deep in gelatin, VE-PAT detected elasticity changes at depths that are difficult to image using other elasticity imaging techniques. We then applied VE-PAT to assess vascular compliance in a human subject and detected a decrease in vascular compliance when an occlusion occurred downstream from the measurement point, demonstrating the potential of VE-PAT in clinical applications such as detection of deep venous thrombosis.

  1. Hemorrhagic shock primes for lung vascular endothelial cell pyroptosis: role in pulmonary inflammation following LPS

    PubMed Central

    Yang, Jie; Zhao, Yanfeng; Zhang, Peng; Li, Yuehua; Yang, Yong; Yang, Yang; Zhu, Junjie; Song, Xiao; Jiang, Gening; Fan, Jie

    2016-01-01

    Hemorrhagic shock (HS) often renders patients more susceptible to lung injury by priming for an exaggerated response to a second infectious stimulus. Acute lung injury (ALI) is a major component of multiple organ dysfunction syndrome following HS and regularly serves as a major cause of patient mortality. The lung vascular endothelium is an active organ that has a central role in the development of ALI through synthesizing and releasing of a number of inflammatory mediators. Cell pyroptosis is a caspase-1-dependent regulated cell death, which features rapid plasma membrane rupture and release of proinflammatory intracellular contents. In this study, we demonstrated an important role of HS in priming for LPS-induced lung endothelial cell (EC) pyroptosis. We showed that LPS through TLR4 activates Nlrp3 (NACHT, LRR, and PYD domains containing protein 3) inflammasome in mouse lung vascular EC, and subsequently induces caspase-1 activation. However, HS induced release of high-mobility group box 1 (HMGB1), which acting through the receptor for advanced glycation end products initiates EC endocytosis of HMGB1, and subsequently triggers a cascade of molecular events, including cathepsin B release from ruptured lysosomes followed by pyroptosome formation and caspase-1 activation. These HS-induced events enhance LPS-induced EC pyroptosis. We further showed that lung vascular EC pyroptosis significantly exaggerates lung inflammation and injury. The present study explores a novel mechanism underlying HS-primed ALI and thus presents a potential therapeutic target for post-HS ALI. PMID:27607578

  2. Hemorrhagic shock primes for lung vascular endothelial cell pyroptosis: role in pulmonary inflammation following LPS.

    PubMed

    Yang, Jie; Zhao, Yanfeng; Zhang, Peng; Li, Yuehua; Yang, Yong; Yang, Yang; Zhu, Junjie; Song, Xiao; Jiang, Gening; Fan, Jie

    2016-01-01

    Hemorrhagic shock (HS) often renders patients more susceptible to lung injury by priming for an exaggerated response to a second infectious stimulus. Acute lung injury (ALI) is a major component of multiple organ dysfunction syndrome following HS and regularly serves as a major cause of patient mortality. The lung vascular endothelium is an active organ that has a central role in the development of ALI through synthesizing and releasing of a number of inflammatory mediators. Cell pyroptosis is a caspase-1-dependent regulated cell death, which features rapid plasma membrane rupture and release of proinflammatory intracellular contents. In this study, we demonstrated an important role of HS in priming for LPS-induced lung endothelial cell (EC) pyroptosis. We showed that LPS through TLR4 activates Nlrp3 (NACHT, LRR, and PYD domains containing protein 3) inflammasome in mouse lung vascular EC, and subsequently induces caspase-1 activation. However, HS induced release of high-mobility group box 1 (HMGB1), which acting through the receptor for advanced glycation end products initiates EC endocytosis of HMGB1, and subsequently triggers a cascade of molecular events, including cathepsin B release from ruptured lysosomes followed by pyroptosome formation and caspase-1 activation. These HS-induced events enhance LPS-induced EC pyroptosis. We further showed that lung vascular EC pyroptosis significantly exaggerates lung inflammation and injury. The present study explores a novel mechanism underlying HS-primed ALI and thus presents a potential therapeutic target for post-HS ALI. PMID:27607578

  3. Diagnosing vascular causes of renal failure.

    PubMed

    Abuelo, J G

    1995-10-15

    The incidence of renal failure due to vascular diseases is increasing. Two reasons for this are the epidemic of atherosclerotic vascular disease in the aging population and the widespread use of vasoactive drugs that can adversely affect renal function. These vascular causes of renal failure include vasomotor disorders such as that associated with nonsteroidal antiinflammatory drugs, small-vessel diseases such as cholesterol crystal embolization, and large-vessel diseases such as renal artery stenosis. These causes of azotemia are less familiar to physicians than more classic causes, such as acute tubular necrosis, and are less likely to be recognized in their early stages. This article describes the various vascular diseases that impair renal function and outlines the steps necessary to identify them. Although some of these conditions, such as renal artery stenosis, can gradually impair function, the vascular causes of acute renal failure are emphasized in this article. Because the vasculitides primarily cause renal failure through secondary glomerulonephritis, they are mentioned only briefly. Extensive testing is rarely necessary because the cause is usually suspected through syndrome recognition. The diagnosis can then be confirmed by the results of one or two additional tests or by improved renal function after treatment.

  4. Collagen vascular disease

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/001223.htm Collagen vascular disease To use the sharing features on ... were previously said to have "connective tissue" or "collagen vascular" disease. We now have names for many ...

  5. [Vascular dementia: facts and controversies].

    PubMed

    Pavlović, Aleksandra; Pavlović, Dragan; Aleksić, Vuk; Sternić, Nadezda

    2013-01-01

    Vascular dementia (VaD) is the second most frequent dementia after Alzheimer's disease, and is diagnosed during lifetime in 20% of demented patients. Five-year survival rate in VaD is 39%, while it is estimated to be 75% in healthy persons of the same age. It is therefore important to make correct diagnosis of VaD early in the course of the disease. Risk factors forVaD are identical to stroke risk factors, and there are significant possibilities for the prevention of vascular cognitive decline. Cognitive decline develops acutely or step-by-step within three months after stroke, but more gradual progression of intellectual decline is also possible. Neurological examination can reveal pyramidal and extrapyramidal signs, pseudobulbar palsy, gait disturbance and urinary incontinence. Neuropsychological profile comprises the loss of cognitive set shifting, decline in word fluency, verbal learning difficulties, perseverations, difficulties in complex figure copying, and in patients with cortically located lesions also problems with speech and praxia. The basis of the diagnosis is, besides history, neurological examination and neuropsychological assessment, computed tomography and/ or magnetic resonance brain imaging. Vascular risk factors control is the most important measure in VaD prevention. Modern guidelines for the treatment of cognitive decline in VaD emphasize that donepezil can be useful in the improvement of cognitive status at the level of Class Ila recommendation at the level of evidence A, while memantine may be useful in patients with mixed VaD and Alzheimer's disease dementia. PMID:23745353

  6. Pazopanib-Induced Severe Acute Pancreatitis.

    PubMed

    Kawakubo, Kazumichi; Hata, Hiroo; Kawakami, Hiroshi; Kuwatani, Masaki; Kawahata, Shuhei; Kubo, Kimitoshi; Imafuku, Keisuke; Kitamura, Shinya; Sakamoto, Naoya

    2015-01-01

    Pazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptors, platelet-derived growth factor receptors, and c-Kit approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Nonselective kinase inhibitors, such as sunitinib and sorafenib, are known to be associated with acute pancreatitis. There are few case reports of severe acute pancreatitis induced by pazopanib treatment. We present a case of severe acute pancreatitis caused by pazopanib treatment for cutaneous angiosarcoma. The patient was an 82-year-old female diagnosed with cutaneous angiosarcoma. She had been refractory to docetaxel treatment and began pazopanib therapy. Three months after pazopanib treatment, CT imaging of the abdomen showed the swelling of the pancreas and surrounding soft tissue inflammation without abdominal pain. After she continued pazopanib treatment for 2 months, she presented with nausea and appetite loss. Abdominal CT showed the worsening of the surrounding soft tissue inflammation of the pancreas. Serum amylase and lipase levels were 296 and 177 IU/l, respectively. She was diagnosed with acute pancreatitis induced by pazopanib treatment and was managed conservatively with discontinuation of pazopanib, but the symptoms did not improve. Subsequently, an abdominal CT scan demonstrated the appearance of a pancreatic pseudocyst. She underwent endoscopic ultrasound-guided pseudocyst drainage using a flared-end fully covered self-expandable metallic stent. Then, the symptoms resolved without recurrence. Due to the remarkable progress of molecular targeted therapy, the oncologist should know that acute pancreatitis was recognized as a potential adverse event of pazopanib treatment and could proceed to severe acute pancreatitis. PMID:26464570

  7. Vascular restoration therapy and bioresorbable vascular scaffold

    PubMed Central

    Wang, Yunbing; Zhang, Xingdong

    2014-01-01

    This article describes the evolution of minimally invasive intervention technologies for vascular restoration therapy from early-stage balloon angioplasty in 1970s, metallic bare metal stent and metallic drug-eluting stent technologies in 1990s and 2000s, to bioresorbable vascular scaffold (BVS) technology in large-scale development in recent years. The history, the current stage, the challenges and the future of BVS development are discussed in detail as the best available approach for vascular restoration therapy. The criteria of materials selection, design and processing principles of BVS, and the corresponding clinical trial results are also summarized in this article. PMID:26816624

  8. Multifocal vascular lesions.

    PubMed

    Levin, Laura E; Lauren, Christine T

    2016-03-01

    Multifocal vascular lesions are important to recognize and appropriately diagnose. Generally first noticed on the skin, multifocal vascular lesions may have systemic involvement. Distinguishing among the different types of multifocal vascular lesions is often based on clinical features; however, radiological imaging and/or biopsy are frequently needed to identify distinct features and guide treatment. Knowledge of the systemic associations that can occur with different vascular anomalies may reduce life-threatening complications, such as coagulopathy, bleeding, cardiac compromise, and neurologic sequelae. This review provides a synopsis of the epidemiology, pathogenesis, presentation, workup, and treatment of several well-recognized multifocal vascular tumors and malformations. PMID:27607324

  9. Initiation of vascular development.

    PubMed

    Ohashi-Ito, Kyoko; Fukuda, Hiroo

    2014-06-01

    The initiation of vascular development occurs during embryogenesis and the development of lateral organs, such as lateral roots and leaves. Understanding the mechanism underlying the initiation of vascular development has been an important goal of plant biologists. Auxin flow is a crucial factor involved in the initiation of vascular development. In addition, recent studies have identified key factors that regulate the establishment of vascular initial cells in embryos and roots. In this review, we summarize the recent findings in this field and discuss the initiation of vascular development.

  10. Amorphous silica nanoparticles impair vascular homeostasis and induce systemic inflammation

    PubMed Central

    Nemmar, Abderrahim; Albarwani, Sulayma; Beegam, Sumaya; Yuvaraju, Priya; Yasin, Javed; Attoub, Samir; Ali, Badreldin H

    2014-01-01

    Amorphous silica nanoparticles (SiNPs) are being used in biomedical, pharmaceutical, and many other industrial applications entailing human exposure. However, their potential vascular and systemic pathophysiologic effects are not fully understood. Here, we investigated the acute (24 hours) systemic toxicity of intraperitoneally administered 50 nm and 500 nm SiNPs in mice (0.5 mg/kg). Both sizes of SiNPs induced a platelet proaggregatory effect in pial venules and increased plasma concentration of plasminogen activator inhibitor-1. Elevated plasma levels of von Willebrand factor and fibrinogen and a decrease in the number of circulating platelets were only seen following the administration of 50 nm SiNPs. The direct addition of SiNPs to untreated mouse blood significantly induced in vitro platelet aggregation in a dose-dependent fashion, and these effects were more pronounced with 50 nm SiNPs. Both sizes of SiNPs increased lactate dehydrogenase activity and interleukin 1β concentration. However, tumor necrosis factor α concentration was only increased after the administration of 50 nm SiNPs. Nevertheless, plasma markers of oxidative stress, including 8-isoprostane, thiobarbituric acid reactive substances, catalase, and glutathione S-transferase, were not affected by SiNPs. The in vitro exposure of human umbilical vein endothelial cells to SiNPs showed a reduced cellular viability, and more potency was seen with 50 nm SiNPs. Both sizes of SiNPs caused a decrease in endothelium-dependent relaxation of isolated small mesenteric arteries. We conclude that amorphous SiNPs cause systemic inflammation and coagulation events, and alter vascular reactivity. Overall, the effects observed with 50 nm SiNPs were more pronounced than those with 500 nm SiNPs. These findings provide new insight into the deleterious effect of amorphous SiNPs on vascular homeostasis. PMID:24936130

  11. Risk factors for acute chemical releases with public health consequences: Hazardous Substances Emergency Events Surveillance in the U.S., 1996–2001

    PubMed Central

    Ruckart, Perri Z; Wattigney, Wendy A; Kaye, Wendy E

    2004-01-01

    Background Releases of hazardous materials can cause substantial morbidity and mortality. To reduce and prevent the public health consequences (victims or evacuations) from uncontrolled or illegally released hazardous substances, a more comprehensive analysis is needed to determine risk factors for hazardous materials incidents. Methods Hazardous Substances Emergency Events Surveillance (HSEES) data from 1996 through 2001 were analyzed using bivariate and multiple logistic regression. Fixed-facility and transportation-related events were analyzed separately. Results For fixed-facility events, 2,327 (8%) resulted in at least one victim and 2,844 (10%) involved ordered evacuations. For transportation-related events, 759 (8%) resulted in at least one victim, and 405 (4%) caused evacuation orders. Fire and/or explosion were the strongest risk factors for events involving either victims or evacuations. Stratified analysis of fixed-facility events involving victims showed a strong association for acid releases in the agriculture, forestry, and fisheries industry. Chlorine releases in fixed-facility events resulted in victims and evacuations in more industry categories than any other substance. Conclusions Outreach efforts should focus on preventing and preparing for fires and explosions, acid releases in the agricultural industry, and chlorine releases in fixed facilities. PMID:15496226

  12. Acute Pancreatitis and Pregnancy

    MedlinePlus

    ... sudden inflammation of the pancreas manifested clinically by abdominal pain, nausea and dehydration that is usually self-limiting ... room for evaluation should they develop any abnormal abdominal pain symptoms. Conclusions While a rare event, acute pancreatitis ...

  13. Missing Teeth Predict Incident Cardiovascular Events, Diabetes, and Death.

    PubMed

    Liljestrand, J M; Havulinna, A S; Paju, S; Männistö, S; Salomaa, V; Pussinen, P J

    2015-08-01

    Periodontitis, the main cause of tooth loss in the middle-aged and elderly, associates with the risk of atherosclerotic vascular disease. The objective was to study the capability of the number of missing teeth in predicting incident cardiovascular diseases (CVDs), diabetes, and all-cause death. The National FINRISK 1997 Study is a Finnish population-based survey of 8,446 subjects with 13 y of follow-up. Dental status was recorded at baseline in a clinical examination by a trained nurse, and information on incident CVD events, diabetes, and death was obtained via national registers. The registered CVD events included coronary heart disease events, acute myocardial infarction, and stroke. In Cox regression analyses, having ≥5 teeth missing was associated with 60% to 140% increased hazard for incident coronary heart disease events (P < 0.020) and acute myocardial infarction (P < 0.010). Incident CVD (P < 0.043), diabetes (P < 0.040), and death of any cause (P < 0.019) were associated with ≥9 missing teeth. No association with stroke was observed. Adding information on missing teeth to established risk factors improved risk discrimination of death (P = 0.0128) and provided a statistically significant net reclassification improvement for all studied end points. Even a few missing teeth may indicate an increased risk of CVD, diabetes, or all-cause mortality. When individual risk factors for chronic diseases are assessed, the number of missing teeth could be a useful additional indicator for general medical practitioners.

  14. Acute heart failure with low cardiac output: can we develop a short-term inotropic agent that does not increase adverse events?

    PubMed

    Campia, Umberto; Nodari, Savina; Gheorghiade, Mihai

    2010-09-01

    Acute heart failure represents an increasingly common cause of hospitalization, and may require the use of inotropic drugs in patients with low cardiac output and evidence of organ hypoperfusion. However, currently available therapies may have deleterious effects and increase mortality. An ideal inotropic drug should restore effective tissue perfusion by enhancing myocardial contractility without causing adverse effects. Such a drug is not available yet. New agents with different biological targets are under clinical development. In particular, istaroxime seems to dissociate the inotropic effect exerted by digitalis (inhibition of the membrane sodium/potassium adenosine triphosphatase) from the arrhythmic effect and to ameliorate diastolic dysfunction (via sarcoendoplasmic reticulum calcium adenosine triphosphatase activation). Additionally, the myosin activator omecamtiv mecarbil appears to have promising characteristics, while genetic therapy has been explored in animal studies only. Further investigations are needed to confirm and expand the effectiveness and safety of these agents in patients with acute heart failure and low cardiac output.

  15. [Effect of alcohol on vascular function].

    PubMed

    Kudo, Risa; Yuui, Katsuya; Kasuda, Shogo; Hatake, Katsuhiko

    2015-06-01

    Vascular function is regulated by a balance of vasoconstriction and vasorelaxation. Disorder in this balance due to alcohol consumption causes various clinical conditions. In this review, we discuss the effects of acute and chronic ethanol consumption on vascular responses, including vasoconstriction, endothelium-dependent vasorelaxation, and nerve-mediated vasorelaxation. Acute ethanol administration induces vasoconstriction in ethanol-naive animals in vitro. Furthermore, ethanol can both potentiate and suppress agonist-induced Ca(2+)-dependent vasoconstriction. Moreover, ethanol augments Ca(2+)-independent vasoconstriction by increasing Ca2+ sensitivity. Endothelium-dependent relaxation is mediated by the nitric oxide (NO) pathway and the endothelium-derived hyperpolarizing factor (EDHF) pathway. Acute ethanol treatment inhibits both NO- and EDHF-mediated relaxation. Furthermore, acute ethanol ingestion can also potentiate and suppress calcitonin gene-related peptide (CGRP)-induced nerve-mediated relaxation. These opposing effects may be due to differences in species or vascular beds. Thus, acute ethanol treatment decreases vasorelaxation, thereby shifting the contraction-relaxation balance towards contraction. Combined, these effects are one mechanism by which acute heavy alcohol consumption causes circulatory disturbances such as vasospasms or ischemic heart disease. In contrast, chronic low-dose ethanol has no effect on vasoconstriction, whereas chronic high-dose ethanol increases vasoconstriction. Additionally, chronic ethanol intake has diminished, unchanged, and even increased effects on nerve-mediated relaxation; therefore, conclusions on these effects are not possible at present. Interestingly, chronic low-dose ethanol administration enhanced endothelium-dependent relaxation; however, higher doses inhibited these responses. Therefore, regular or light-to-moderate alcohol intake increases vasorelaxation and may suppress elevated blood pressure, whereas

  16. Role of antiplatelet drugs in the prevention of cardiovascular events.

    PubMed

    Tendera, Michal; Wojakowski, Wojciech

    2003-06-15

    Antiplatelet drugs have an established place in the prevention of vascular events in a variety of clinical conditions, such as myocardial infarction, stroke and cardiovascular death. Both European and American guidelines recommend the use of antiplatelet drugs in patients with established coronary heart disease and other atherosclerotic disease. In high-risk patients, such as those with post-acute myocardial infarction (AMI), ischaemic stroke or transient ischaemic attack, and in patients with stable or unstable angina, peripheral arterial occlusive disease or atrial fibrillation, antiplatelet treatment may reduce the risk of a serious cardiovascular event by approximately 25%, including reduction of non-fatal myocardial infarction by 1/6, non-fatal stroke by 1/4 and cardiovascular death by 1/6. Some data indicate that antiplatelet drugs may also have a role in primary prevention. In people who are aged over 65 years, or have hypertension, hypercholesterolaemia, diabetes, obesity or familial history of myocardial infarction at young age, aspirin may reduce both cardiovascular deaths and total cardiovascular events. Aspirin has been studied and used most extensively. It may exert its beneficial effect not only by acting on platelets, but also by other mechanisms, such as preventing thromboxane A2 (TXA2)-induced vasoconstriction or reducing inflammation. Indeed, experimental data show that low-dose aspirin may suppress vascular inflammation and thereby increase the stability of atherosclerotic plaque. Moreover, in human studies, aspirin seems to be most effective in those with elevated C-reactive protein levels. Vascular events, however, do occur despite aspirin administration. This may be due to platelet activation by pathways not blocked by aspirin, intake of drugs that interfere with aspirin effect or aspirin resistance. In the CAPRIE (Clopidogrel vs. Aspirin in Patients at Risk of Ischaemic Events) study, long-term clopidogrel administered to patients with

  17. Vascular oxidant stress and inflammation in hyperhomocysteinemia.

    PubMed

    Papatheodorou, Louisa; Weiss, Norbert

    2007-11-01

    Elevated plasma levels of homocysteine are a metabolic risk factor for atherosclerotic vascular disease, as shown in numerous clinical studies that linked elevated homocysteine levels to de novo and recurrent cardiovascular events. High levels of homocysteine promote oxidant stress in vascular cells and tissue because of the formation of reactive oxygen species (ROS), which have been strongly implicated in the development of atherosclerosis. In particular, ROS have been shown to cause endothelial injury, dysfunction, and activation. Elevated homocysteine stimulates proinflammatory pathways in vascular cells, resulting in leukocyte recruitment to the vessel wall, mediated by the expression of adhesion molecules on endothelial cells and circulating monocytes and neutrophils, in the infiltration of leukocytes into the arterial wall mediated by increased secretion of chemokines, and in the differentiation of monocytes into cholesterol-scavenging macrophages. Furthermore, it stimulates the proliferation of vascular smooth muscle cells followed by the production of extracellular matrix. Many of these events involve redox-sensitive signaling events, which are promoted by elevated homocysteine, and result in the formation of atherosclerotic lesions. In this article, we review current knowledge about the role of homocysteine on oxidant stress-mediated vascular inflammation during the development of atherosclerosis.

  18. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

    For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467

  19. Population-Based Study of Incidence, Risk Factors, Outcome, and Prognosis of Ischemic Peripheral Arterial Events

    PubMed Central

    Howard, Dominic P.J.; Banerjee, Amitava; Fairhead, Jack F.; Hands, Linda; Silver, Louise E.; Rothwell, Peter M.

    2015-01-01

    Background— There are few published data on the incidence and long-term outcomes of critical limb ischemia, acute limb ischemia, or acute visceral ischemia with which to inform health service planning, to monitor prevention, and to enable risk prediction. Methods and Results— In a prospective population-based study (Oxfordshire, UK; 2002–2012), we determined the incidence and outcome of all acute peripheral arterial events in a population of 92 728. Risk factors were assessed by comparison with the underlying population. A total of 510 acute events occurred in 386 patients requiring 803 interventions. Two hundred twenty-one patients (59.3%) were ≥75 years of age, and 98 (26.3%) were ≥85 years old. Two hundred thirty patients (62.3%) were independent before the event, but 270 (73.4%) were dead or dependent at the 6-month follow-up, and 328 (88.9%) were dead or dependent at 5 years. The 30-day survival was lowest for patients with acute visceral ischemia (28.2%) compared with acute limb ischemia (75.3%) and critical limb ischemia (92.6%; P<0.001). Risk factors (all P<0.001) were hypertension (age- and sex-adjusted risk ratio, 2.75; 95% confidence interval, 1.95–3.90), smoking (adjusted risk ratio, 2.14; 95% confidence interval, 1.37–3.34), and diabetes mellitus (adjusted risk ratio, 3.01; 95% confidence interval, 1.69–5.35), particularly for critical limb ischemia (adjusted risk ratio, 5.96; 95% confidence interval, 3.15–11.26). Two hundred eighty-eight patients (77.2%) had known previous cardiovascular disease, and 361 (96.8%) had vascular risk factors, but only 203 (54.4%) were on an antiplatelet and only 166 (44.5%) were on a statin. Although 260 patients (69.7%) were taking antihypertensives, 42.9% of all blood pressures recorded during the 5 years before the event were >140/90 mm Hg. Of 88 patients (23.6%) with incident cardioembolic events, 62 had known atrial fibrillation (diagnosed before the event), of whom only 14.5% were

  20. Neurogenic vascular headaches, food and chemical triggers.

    PubMed

    Trotsky, M B

    1994-04-01

    Recent evidence has demonstrated that neurogenic vascular headaches are a combination of neurological primary events and secondary vasomotor changes. The neurological events involve the hypothalamus and sensory cortex with sympathetic hypofunction and noradrenergic abnormalities. A platelet theory has been proposed but has not really been confirmed as a legitimate cause of the neurogenic vascular headaches. Food and chemicals in foods can act as a precipitating factor in the food-sensitive neurogenic vascular headache patient. In these patients evidence is now being demonstrated to confirm this, but larger patient studies are needed. The food-sensitive migraine patient and cluster headache patient must give a good history and food diary to go along with active challenges and provocative testing in order to determine the causative foods. Any concomitant allergies of inhalants or environmentals must also be treated. The treatment modalities of elimination and rotation diets or provocation neutralization may successfully control the headaches without the need for continuous medications.

  1. Imaging Pediatric Vascular Lesions

    PubMed Central

    Nguyen, Tuyet A.; Krakowski, Andrew C.; Naheedy, John H.; Kruk, Peter G.

    2015-01-01

    Vascular anomalies are commonly encountered in pediatric and dermatology practices. Most of these lesions are benign and easy to diagnose based on history and clinical exam alone. However, in some cases the diagnosis may not be clear. This may be of particular concern given that vascular anomalies may occasionally be associated with an underlying syndrome, congenital disease, or serious, life-threatening condition. Defining the type of vascular lesion early and correctly is particularly important to determine the optimal approach to management and treatment of each patient. The care of pediatric patients often requires collaboration from a multitude of specialties including pediatrics, dermatology, plastic surgery, radiology, ophthalmology, and neurology. Although early characterization of vascular lesions is important, consensus guidelines regarding the evaluation and imaging of vascular anomalies does not exist to date. Here, the authors provide an overview of pediatric vascular lesions, current classification systems for characterizing these lesions, the various imaging modalities available, and recommendations for appropriate imaging evaluation. PMID:26705446

  2. Patient and System-Related Delays of Emergency Medical Services Use in Acute ST-Elevation Myocardial Infarction: Results from the Third Gulf Registry of Acute Coronary Events (Gulf RACE-3Ps)

    PubMed Central

    AlHabib, Khalid F.; Sulaiman, Kadhim; Al Suwaidi, Jassim; Almahmeed, Wael; Alsheikh-Ali, Alawi A.; Amin, Haitham; Al Jarallah, Mohammed; Alfaleh, Hussam F.; Panduranga, Prashanth; Hersi, Ahmad; Kashour, Tarek; Al Aseri, Zohair; Ullah, Anhar; Altaradi, Hani B.; Nur Asfina, Kazi; Welsh, Robert C.; Yusuf, Salim

    2016-01-01

    Background Little is known about Emergency Medical Services (EMS) use and pre-hospital triage of patients with acute ST-elevation myocardial infarction (STEMI) in Arabian Gulf countries. Methods Clinical arrival and acute care within 24 h of STEMI symptom onset were compared between patients transferred by EMS (Red Crescent and Inter-Hospital) and those transferred by non-EMS means. Data were retrieved from a prospective registry of 36 hospitals in 6 Arabian Gulf countries, from January 2014 to January 2015. Results We enrolled 2,928 patients; mean age, 52.7 (SD ±11.8) years; 90% men; and 61.7% non-Arabian Gulf citizens. Only 753 patients (25.7%) used EMS; which was mostly via Inter-Hospital EMS (22%) rather than direct transfer from the scene to the hospital by the Red Crescent (3.7%). Compared to the non-EMS group, the EMS group was more likely to arrive initially at a primary or secondary health care facility; thus, they had longer median symptom-onset-to-emergency department arrival times (218 vs. 158 min; p˂.001); they were more likely to receive primary percutaneous coronary interventions (62% vs. 40.5%, p = 0.02); they had shorter door-to-needle times (38 vs. 42 min; p = .04); and shorter door-to-balloon times (47 vs. 83 min; p˂.001). High EMS use was independently predicted mostly by primary/secondary school educational levels and low or moderate socioeconomic status. Low EMS use was predicted by a history of angina and history of percutaneous coronary intervention. The groups had similar in-hospital deaths and outcomes. Conclusion Most acute STEMI patients in the Arabian Gulf region did not use EMS services. Improving Red Crescent infrastructure, establishing integrated STEMI networks, and launching educational public campaigns are top health care system priorities. PMID:26807577

  3. Understanding the Pathophysiology and Challenges of Development of Medical Countermeasures for Radiation-Induced Vascular/Endothelial Cell Injuries: Report of a NIAID Workshop, August 20, 2015

    PubMed Central

    Satyamitra, Merriline M.; DiCarlo, Andrea L.; Taliaferro, Lanyn

    2016-01-01

    After the events of September 11, 2001, a decade of research on the development of medical countermeasures (MCMs) to treat victims of a radiological incident has yielded two FDA-approved agents to mitigate acute radiation syndrome. These licensed agents specifically target the mitigation of radiation-induced neutropenia and infection potential, while the ramifications of the exposure event in a public health emergency incident could include the entire body, causing additional acute and/or delayed organ/tissue injuries. Anecdotal data as well as recent findings from both radiation accident survivors and animal experiments implicate radiation-induced injury or dysfunction of the vascular endothelium leading to tissue and organ injuries. There are significant gaps in our understanding of the disease processes and progression, as well as the optimum approaches to develop medical countermeasures to mitigate radiation vascular injury. To address this issue, the Radiation and Nuclear Countermeasures Program of the National Institute of Allergy and Infectious Diseases (NIAID) organized a one-day workshop to examine the current state of the science in radiation-induced vascular injuries and organ dysfunction, the natural history of the pathophysiology and the product development maturity of potential medical countermeasures to treat these injuries. Meeting presentations were followed by a NIAID-led open discussion among academic investigators, industry researchers and government agency representatives. This article provides a summary of these presentations and subsequent discussion from the workshop. PMID:27387859

  4. Understanding the Pathophysiology and Challenges of Development of Medical Countermeasures for Radiation-Induced Vascular/Endothelial Cell Injuries: Report of a NIAID Workshop, August 20, 2015.

    PubMed

    Satyamitra, Merriline M; DiCarlo, Andrea L; Taliaferro, Lanyn

    2016-08-01

    After the events of September 11, 2001, a decade of research on the development of medical countermeasures (MCMs) to treat victims of a radiological incident has yielded two FDA-approved agents to mitigate acute radiation syndrome. These licensed agents specifically target the mitigation of radiation-induced neutropenia and infection potential, while the ramifications of the exposure event in a public health emergency incident could include the entire body, causing additional acute and/or delayed organ/tissue injuries. Anecdotal data as well as recent findings from both radiation accident survivors and animal experiments implicate radiation-induced injury or dysfunction of the vascular endothelium leading to tissue and organ injuries. There are significant gaps in our understanding of the disease processes and progression, as well as the optimum approaches to develop medical countermeasures to mitigate radiation vascular injury. To address this issue, the Radiation and Nuclear Countermeasures Program of the National Institute of Allergy and Infectious Diseases (NIAID) organized a one-day workshop to examine the current state of the science in radiation-induced vascular injuries and organ dysfunction, the natural history of the pathophysiology and the product development maturity of potential medical countermeasures to treat these injuries. Meeting presentations were followed by a NIAID-led open discussion among academic investigators, industry researchers and government agency representatives. This article provides a summary of these presentations and subsequent discussion from the workshop. PMID:27387859

  5. Plant vascular development: from early specification to differentiation.

    PubMed

    De Rybel, Bert; Mähönen, Ari Pekka; Helariutta, Yrjö; Weijers, Dolf

    2016-01-01

    Vascular tissues in plants are crucial to provide physical support and to transport water, sugars and hormones and other small signalling molecules throughout the plant. Recent genetic and molecular studies have identified interconnections among some of the major signalling networks that regulate plant vascular development. Using Arabidopsis thaliana as a model system, these studies enable the description of vascular development from the earliest tissue specification events during embryogenesis to the differentiation of phloem and xylem tissues. Moreover, we propose a model for how oriented cell divisions give rise to a three-dimensional vascular bundle within the root meristem.

  6. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute; Acute bladder infection; Acute bacterial cystitis ... International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 ...

  7. Stress-induced dura vascular permeability does not develop in mast cell-deficient and neurokinin-1 receptor knockout mice.

    PubMed

    Kandere-Grzybowska, Kristiana; Gheorghe, Daniela; Priller, Josef; Esposito, Pamela; Huang, Man; Gerard, Norma; Theoharides, Theoharis C

    2003-08-01

    Migraine headaches are often precipitated by stress and seem to involve neurogenic inflammation (NI) of the dura mater associated with the sensation of throbbing pain. Trigeminal nerve stimulation had been reported to activate rat dura mast cells and increase vascular permeability, effects inhibited by neonatal pretreatment with capsaicin implicating sensory neuropeptides, such as substance P (SP). The aim of the present study was to investigate NI, assessed by extravasation of 99-Technetium-gluceptate (99Tc-G), as well as the role of mast cells, SP and its receptor (NK-1R) in dura mater of mice in response to acute stress. Restraint stress for thirty min significantly increased 99Tc-G extravasation in the dura mater of C57BL mice. This effect was absent in W/W(v) mast cell-deficient mice and NK-1 receptor knockout mice (NK-1R-/-), but was unaltered in SP knockout mice (SP-/-). Acute restraint stress also resulted in increased dura mast cell activation in C57BL mice, but not in NK-1R-/- mice. These data demonstrate for the first time that acute stress triggers NI and mast cell activation in mouse dura mater through the activation of NK-1 receptors. The fact that SP-/- mice had intact vascular permeability response to stress indicates that some other NK-1 receptor agonist may substitute for SP. These results may help explain initial events in pathogenesis of stress-induced migraines.

  8. Behçet Disease With Vascular Involvement

    PubMed Central

    Alibaz-Oner, Fatma; Karadeniz, Aslı; Yılmaz, Sema; Balkarlı, Ayşe; Kimyon, Gezmiş; Yazıcı, Ayten; Çınar, Muhammet; Yılmaz, Sedat; Yıldız, Fatih; Bilge, Şule Yaşar; Bilgin, Emre; Coskun, Belkis Nihan; Omma, Ahmet; Çetin, Gözde Yıldırım; Çağatay, Yonca; Karaaslan, Yaşar; Sayarlıoğlu, Mehmet; Pehlivan, Yavuz; Kalyoncu, Umut; Karadağ, Ömer; Kaşifoğlu, Timuçin; Erken, Eren; Pay, Salih; Çefle, Ayşe; Kısacık, Bünyamin; Onat, Ahmet Mesut; Çobankara, Veli; Direskeneli, Haner

    2015-01-01

    Abstract Vascular involvement is one of the major causes of mortality and morbidity in Behçet disease (BD). There are no controlled studies for the management of vascular BD (VBD), and according to the EULAR recommendations, only immunosuppressive (IS) agents are recommended. In this study, we aimed to investigate the therapeutic approaches chosen by Turkish physicians during the initial event and relapses of VBD and the association of different treatment options with the relapses retrospectively. Patients with BD (n = 936, female/male: 347/589, mean age: 37.6 ± 10.8) classified according to ISG criteria from 15 rheumatology centers in Turkey were included. The demographic data, clinical characteristics of the first vascular event and relapses, treatment protocols, and data about complications were acquired. VBD was observed in 27.7% (n = 260) of the patients during follow-up. In 57.3% of the VBD patients, vascular involvement was the presenting sign of the disease. After the first vascular event, ISs were given to 88.8% and AC treatment to 59.8% of the patients. Median duration of AC treatment was 13 months (1–204) and ISs, 22 months (1–204). Minor hemorrhage related to AC treatment was observed in 7 (4.7%) patients. A second vascular event developed in 32.9% (n = 86) of the patients. The vascular relapse rate was similar between patients taking only ISs and AC plus IS treatments after the first vascular event (29.1% vs 22.4%, P = 0.28) and was significantly higher in group taking only ACs than taking only ISs (91.6% vs 29.1%, P < 0.001). During follow-up, a third vascular event developed in 17 (n = 6.5%) patients. The relapse rate was also similar between the patients taking only ISs and AC plus IS treatments after second vascular event (25.3% vs 20.8%, P = 0.93). When multivariate analysis was performed, development of vascular relapse negatively correlated with only IS treatments. We did not find any additional positive

  9. Society for Vascular Medicine

    MedlinePlus

    ... Sessions June 14-17, 2017 Sheraton New Orleans New Orleans, LA USA Board Review Course June 16-18, 2017 SVM in the Vascular Lab June 17, 2017 Learn more Patient Information Pages from Vascular Medicine October 2016 Smoking Cessation More info for patients. SVM Case ...

  10. [Vascular graft prosthesis].

    PubMed

    Chakfé, N; Dieval, F; Thaveau, F; Rinckenbach, S; Hassani, O; Camelot, G; Durand, B; Kretz, J-G

    2004-06-01

    Performed since the 1950s, vascular grafting has opened modern era of vascular surgery. Autologous venous grafts are of first choice for revascularisation of small arteries. Synthetic grafts are mainly modelled using microporous polytetrafluoroethylene or terephtalate polyethylene. These prosthesis are mainly used for revascularization of medium and large size arteries. PMID:15220107

  11. 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.

  12. 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. PMID:27206743

  13. [Vascular factors in glaucoma].

    PubMed

    Mottet, B; Aptel, F; Geiser, M; Romanet, J P; Chiquet, C

    2015-12-01

    The exact pathophysiology of glaucoma is not fully understood. Understanding of the vascular pathophysiology of glaucoma requires: knowing the techniques for measuring ocular blood flow and characterizing the topography of vascular disease and the mechanisms involved in this neuropathy. A decreased mean ocular perfusion pressure and a loss of vascular autoregulation are implicated in glaucomatous disease. Early decrease in ocular blood flow has been identified in primary open-angle glaucoma and normal pressure glaucoma, contributing to the progression of optic neuropathy. The vascular damage associated with glaucoma is present in various vascular territories within the eye (from the ophthalmic artery to the retina) and is characterized by a decrease in basal blood flow associated with a dysfunction of vasoregulation.

  14. [Vascular factors in glaucoma].

    PubMed

    Mottet, B; Aptel, F; Geiser, M; Romanet, J P; Chiquet, C

    2015-12-01

    The exact pathophysiology of glaucoma is not fully understood. Understanding of the vascular pathophysiology of glaucoma requires: knowing the techniques for measuring ocular blood flow and characterizing the topography of vascular disease and the mechanisms involved in this neuropathy. A decreased mean ocular perfusion pressure and a loss of vascular autoregulation are implicated in glaucomatous disease. Early decrease in ocular blood flow has been identified in primary open-angle glaucoma and normal pressure glaucoma, contributing to the progression of optic neuropathy. The vascular damage associated with glaucoma is present in various vascular territories within the eye (from the ophthalmic artery to the retina) and is characterized by a decrease in basal blood flow associated with a dysfunction of vasoregulation. PMID:26597554

  15. Early Vascular Aging: A New Target for Hypertension Treatment.

    PubMed

    Papakatsika, Sofia; Stabouli, Stella; Antza, Christina; Kotsis, Vasilios

    2016-01-01

    Vascular aging represents a progressive procedure involving biochemical, enzymatic, and cellular changes of the vascular tree. Early vascular aging (EVA), is defined as the inappropriate for age of vascular damage. Increased for age arterial stiffness is a biomarker that should be considered as a cardiovascular (CV) risk factor that can be manipulated. EVA is a new tool for guidance in everyday clinical praxis for patients at increased CV risk or a positive family history of early onset of cardiovascular events, such as stroke or coronary artery disease. Understanding the mechanisms promoting or protecting from EVA, a process that is in close relationship with CV diseases. The role of hypertension treatment against the development of vascular damage is important and different strategies could have a considerable impact on future vascular health. PMID:26548304

  16. Early Vascular Aging: A New Target for Hypertension Treatment.

    PubMed

    Papakatsika, Sofia; Stabouli, Stella; Antza, Christina; Kotsis, Vasilios

    2016-01-01

    Vascular aging represents a progressive procedure involving biochemical, enzymatic, and cellular changes of the vascular tree. Early vascular aging (EVA), is defined as the inappropriate for age of vascular damage. Increased for age arterial stiffness is a biomarker that should be considered as a cardiovascular (CV) risk factor that can be manipulated. EVA is a new tool for guidance in everyday clinical praxis for patients at increased CV risk or a positive family history of early onset of cardiovascular events, such as stroke or coronary artery disease. Understanding the mechanisms promoting or protecting from EVA, a process that is in close relationship with CV diseases. The role of hypertension treatment against the development of vascular damage is important and different strategies could have a considerable impact on future vascular health.

  17. Frequent epigenetic inactivation of KIBRA, an upstream member of the Salvador/Warts/Hippo (SWH) tumor suppressor network, is associated with specific genetic event in B-cell acute lymphocytic leukemia.

    PubMed

    Hill, Victoria K; Dunwell, Thomas L; Catchpoole, Daniel; Krex, Dietmar; Brini, Anna T; Griffiths, Mike; Craddock, Charles; Maher, Eamonn R; Latif, Farida

    2011-03-01

    The WW-domain containing protein KIBRA has recently been identified as a new member of the Salvador/Warts/Hippo (SWH) pathway in Drosophila and is shown to act as a tumor suppressor gene in Drosophila. This pathway is conserved in humans and members of the pathway have been shown to act as tumor suppressor genes in mammalian systems. We determined the methylation status of the 5' CpG island associated with the KIBRA gene in human cancers. In a large panel of cancer cell lines representing common epithelial cancers KIBRA was unmethylated. But in pediatric acute lymphocytic leukemia (ALL) cell lines KIBRA showed frequent hypermethylation and silencing of gene expression, which could be reversed by treatment with 5-aza-2'-deoxycytidine. In ALL patient samples KIBRA was methylated in 70% B-ALL but was methylated in < 20% T-ALL leukemia (p = 0.0019). In B-ALL KIBRA methylation was associated with ETV6/RUNX1 [t(12;21) (p13;q22)] chromosomal translocation (p = 0.0082) phenotype, suggesting that KIBRA may play an important role in t(12;21) leukemogenesis. In ALL paired samples at diagnosis and remission KIBRA methylation was seen in diagnostic but not in any of the remission samples accompanied by loss of KIBRA expression in disease state compared to patients in remission. Hence KIBRA methylation occurs frequently in B-cell acute lymphocytic leukemia but not in epithelial cancers and is linked to specific genetic event in B-ALL.

  18. Novel Paradigms for Dialysis Vascular Access: Upstream Hemodynamics and Vascular Remodeling in Dialysis Access Stenosis

    PubMed Central

    Ene-Iordache, Bogdan

    2013-01-01

    Summary Failure of hemodialysis access is caused mostly by venous intimal hyperplasia, a fibro-muscular thickening of the vessel wall. The pathogenesis of venous neointimal hyperplasia in primary arteriovenous fistulae consists of processes that have been identified as upstream and downstream events. Upstream events are the initial events producing injury of the endothelial layer (surgical trauma, hemodynamic shear stress, vessel wall injury due to needle punctures, etc.). Downstream events are the responses of the vascular wall at the endothelial injury that consist of a cascade of processes including leukocyte adhesion, migration of smooth muscle cells from the media to the intimal layer, and proliferation. In arteriovenous fistulae, the stenoses occur in specific sites, consistently related to the local hemodynamics determined by the vessel geometry and blood flow pattern. Recent findings that the localization of these sites matches areas of disturbed flow may add new insights into the pathogenesis of neointimal hyperplasia in the venous side of vascular access after the creation of the anastomosis. The detailed study of fluid flow motion acting on the vascular wall in anastomosed vessels and in the arm vasculature at the patient-specific level may help to elucidate the role of hemodynamics in vascular remodeling and neointimal hyperplasia formation. These computational approaches may also help in surgical planning for the amelioration of clinical outcome. This review aims to discuss the role of the disturbed flow condition in acting as upstream event in the pathogenesis of venous intimal hyperplasia and in producing subsequent local vascular remodeling in autogenous arteriovenous fistulae used for hemodialysis access. The potential use of blood flow analysis in the management of vascular access is also discussed. PMID:23990161

  19. NOTCH2 and FLT3 gene mis-splicings are common events in patients with acute myeloid leukemia (AML): new potential targets in AML

    PubMed Central

    Bar-Natan, Michal; Haibe-Kains, Benjamin; Pilarski, Patrick M.; Bach, Christian; Pevzner, Samuel; Calimeri, Teresa; Avet-Loiseau, Herve; Lode, Laurence; Verselis, Sigitas; Fox, Edward A.; Galinsky, Ilene; Mathews, Steven; Dagogo-Jack, Ibiayi; Wadleigh, Martha; Steensma, David P.; Motyckova, Gabriela; Deangelo, Daniel J.; Quackenbush, John; Tenen, Daniel G.; Stone, Richard M.; Griffin, James D.

    2014-01-01

    Our previous studies revealed an increase in alternative splicing of multiple RNAs in cells from patients with acute myeloid leukemia (AML) compared with CD34+ bone marrow cells from normal donors. Aberrantly spliced genes included a number of oncogenes, tumor suppressor genes, and genes involved in regulation of apoptosis, cell cycle, and cell differentiation. Among the most commonly mis-spliced genes (>70% of AML patients) were 2, NOTCH2 and FLT3, that encode myeloid cell surface proteins. The splice variants of NOTCH2 and FLT3 resulted from complete or partial exon skipping and utilization of cryptic splice sites. Longitudinal analyses suggested that NOTCH2 and FLT3 aberrant splicing correlated with disease status. Correlation analyses between splice variants of these genes and clinical features of patients showed an association between NOTCH2-Va splice variant and overall survival of patients. Our results suggest that NOTCH2 and FLT3 mis-splicing is a common characteristic of AML and has the potential to generate transcripts encoding proteins with altered function. Thus, splice variants of these genes might provide disease markers and targets for novel therapeutics. PMID:24574459

  20. Vascular Access in Children

    SciTech Connect

    Krishnamurthy, Ganesh Keller, Marc S.

    2011-02-15

    Establishment of stable vascular access is one of the essential and most challenging procedures in a pediatric hospital. Many clinical specialties provide vascular service in a pediatric hospital. At the top of the 'expert procedural pyramid' is the pediatric interventional radiologist, who is best suited and trained to deliver this service. Growing awareness regarding the safety and high success rate of vascular access using image guidance has led to increased demand from clinicians to provide around-the-clock vascular access service by pediatric interventional radiologists. Hence, the success of a vascular access program, with the pediatric interventional radiologist as the key provider, is challenging, and a coordinated multidisciplinary team effort is essential for success. However, there are few dedicated pediatric interventional radiologists across the globe, and also only a couple of training programs exist for pediatric interventions. This article gives an overview of the technical aspects of pediatric vascular access and provides useful tips for obtaining vascular access in children safely and successfully using image guidance.

  1. Impact of dose intensity of ponatinib on selected adverse events: Multivariate analyses from a pooled population of clinical trial patients.

    PubMed

    Dorer, David J; Knickerbocker, Ronald K; Baccarani, Michele; Cortes, Jorge E; Hochhaus, Andreas; Talpaz, Moshe; Haluska, Frank G

    2016-09-01

    Ponatinib is approved for adults with refractory chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia, including those with the T315I BCR-ABL1 mutation. We pooled data from 3 clinical trials (N=671) to determine the impact of ponatinib dose intensity on the following adverse events: arterial occlusive events (cardiovascular, cerebrovascular, and peripheral vascular events), venous thromboembolic events, cardiac failure, thrombocytopenia, neutropenia, hypertension, pancreatitis, increased lipase, increased alanine aminotransferase, increased aspartate aminotransferase, rash, arthralgia, and hypertriglyceridemia. Multivariate analyses allowed adjustment for covariates potentially related to changes in dosing or an event. Logistic regression analysis identified significant associations between dose intensity and most events after adjusting for covariates. Pancreatitis, rash, and cardiac failure had the strongest associations with dose intensity (odds ratios >2). Time-to-event analyses showed significant associations between dose intensity and risk of arterial occlusive events and each subcategory. Further, these analyses suggested that a lag exists between a change in dose and the resulting change in event risk. No significant association between dose intensity and risk of venous thromboembolic events was evident. Collectively, these findings suggest a potential causal relationship between ponatinib dose and certain adverse events and support prospective investigations of approaches to lower average ponatinib dose intensity. PMID:27505637

  2. Impact of dose intensity of ponatinib on selected adverse events: Multivariate analyses from a pooled population of clinical trial patients.

    PubMed

    Dorer, David J; Knickerbocker, Ronald K; Baccarani, Michele; Cortes, Jorge E; Hochhaus, Andreas; Talpaz, Moshe; Haluska, Frank G

    2016-09-01

    Ponatinib is approved for adults with refractory chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia, including those with the T315I BCR-ABL1 mutation. We pooled data from 3 clinical trials (N=671) to determine the impact of ponatinib dose intensity on the following adverse events: arterial occlusive events (cardiovascular, cerebrovascular, and peripheral vascular events), venous thromboembolic events, cardiac failure, thrombocytopenia, neutropenia, hypertension, pancreatitis, increased lipase, increased alanine aminotransferase, increased aspartate aminotransferase, rash, arthralgia, and hypertriglyceridemia. Multivariate analyses allowed adjustment for covariates potentially related to changes in dosing or an event. Logistic regression analysis identified significant associations between dose intensity and most events after adjusting for covariates. Pancreatitis, rash, and cardiac failure had the strongest associations with dose intensity (odds ratios >2). Time-to-event analyses showed significant associations between dose intensity and risk of arterial occlusive events and each subcategory. Further, these analyses suggested that a lag exists between a change in dose and the resulting change in event risk. No significant association between dose intensity and risk of venous thromboembolic events was evident. Collectively, these findings suggest a potential causal relationship between ponatinib dose and certain adverse events and support prospective investigations of approaches to lower average ponatinib dose intensity.

  3. (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans.

    PubMed

    Schroeter, Hagen; Heiss, Christian; Balzer, Jan; Kleinbongard, Petra; Keen, Carl L; Hollenberg, Norman K; Sies, Helmut; Kwik-Uribe, Catherine; Schmitz, Harold H; Kelm, Malte

    2006-01-24

    Epidemiological and medical anthropological investigations suggest that flavanol-rich foods exert cardiovascular health benefits. Endothelial dysfunction, a prognostically relevant key event in atherosclerosis, is characterized by a decreased bioactivity of nitric oxide (NO) and impaired flow-mediated vasodilation (FMD). We show in healthy male adults that the ingestion of flavanol-rich cocoa was associated with acute elevations in levels of circulating NO species, an enhanced FMD response of conduit arteries, and an augmented microcirculation. In addition, the concentrations and the chemical profiles of circulating flavanol metabolites were determined, and multivariate regression analyses identified (-)-epicatechin and its metabolite, epicatechin-7-O-glucuronide, as independent predictors of the vascular effects after flavanol-rich cocoa ingestion. A mixture of flavanols/metabolites, resembling the profile and concentration of circulating flavanol compounds in plasma after cocoa ingestion, induced a relaxation in preconstricted rabbit aortic rings ex vivo, thus mimicking acetylcholine-induced relaxations. Ex vivo flavanol-induced relaxation, as well as the in vivo increases in FMD, were abolished by inhibition of NO synthase. Oral administration of chemically pure (-)-epicatechin to humans closely emulated acute vascular effects of flavanol-rich cocoa. Finally, the concept that a chronic intake of high-flavanol diets is associated with prolonged, augmented NO synthesis is supported by data that indicate a correlation between the chronic consumption of a cocoa flavanol-rich diet and the augmented urinary excretion of NO metabolites. Collectively, our data demonstrate that the human ingestion of the flavanol (-)-epicatechin is, at least in part, causally linked to the reported vascular effects observed after the consumption of flavanol-rich cocoa. PMID:16418281

  4. Rationale and design of a secondary prevention trial of lowering normal plasma cholesterol levels after acute myocardial infarction: the Cholesterol and Recurrent Events trial (CARE)

    PubMed

    Sacks, F M; Pfeffer, M A; Moye', L; Brown, L E; Hamm, P; Cole, T G; Hawkins, C M; Braunwald, E

    1991-12-01

    Recent clinical trials of primary and secondary prevention of cardiovascular disease have demonstrated that lowering plasma cholesterol decreases the incidence of coronary heart disease in patients with elevated plasma cholesterol. However, it is not known whether patients with established coronary artery disease and normal plasma cholesterol can be benefited. Several previous prevention trials reviewed in this report found that patients who had plasma cholesterol levels at baseline in the upper portion of the eligibility range (e.g., greater than 240 mg/dl) received greater benefit from hypolipidemic diet or drug therapy than patients who had lower plasma cholesterol levels at baseline. The recent availability of drugs that are more potent and less prone to cause adverse reactions than previous regimens permits this important question to be addressed. The Cholesterol and Recurrent Events trial is testing whether pravastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, will decrease the sum of fatal coronary heart disease and nonfatal myocardial infarction (MI) in patients who have recovered from a MI and who have normal total cholesterol levels. Fatal cardiovascular disease and total mortality are important secondary end points. The trial is enrolling 4,000 men and women from 80 centers throughout North America, age 21 to 75 years, who have survived MI for 3 to 20 months, who have plasma total cholesterol less than 240 mg/dl (6.2 mmol/liter) and low-density cholesterol of 115 to 174 mg/dl (3.0 to 4.5 mmol/liter), and who are representative of the general population of patients with MI. Patients are randomized to either active or inactive drug therapy. Active therapy consists of pravastatin, 40 mg/day, designed to achieve an average decrease in low-density lipoprotein cholesterol of approximately 30%, and an increase in high-density lipoprotein of 5%. The average duration of follow-up will be greater than or equal to 5 years. To protect against a lower

  5. High event-free survival rate with minimum-dose-anthracycline treatment in childhood acute promyelocytic leukaemia: a nationwide prospective study by the Japanese Paediatric Leukaemia/Lymphoma Study Group.

    PubMed

    Takahashi, Hiroyuki; Watanabe, Tomoyuki; Kinoshita, Akitoshi; Yuza, Yuki; Moritake, Hiroshi; Terui, Kiminori; Iwamoto, Shotaro; Nakayama, Hideki; Shimada, Akira; Kudo, Kazuko; Taki, Tomohiko; Yabe, Miharu; Matsushita, Hiromichi; Yamashita, Yuka; Koike, Kazutoshi; Ogawa, Atsushi; Kosaka, Yoshiyuki; Tomizawa, Daisuke; Taga, Takashi; Saito, Akiko M; Horibe, Keizo; Nakahata, Tatsutoshi; Miyachi, Hayato; Tawa, Akio; Adachi, Souichi

    2016-08-01

    We evaluated the efficacy of treatment using reduced cumulative doses of anthracyclines in children with acute promyelocytic leukaemia (APL) in the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-P05 study. All patients received two and three subsequent courses of induction and consolidation chemotherapy respectively, consisting of all-trans retinoic acid (ATRA), cytarabine and anthracyclines, followed by maintenance therapy with ATRA. Notably, a single administration of anthracyclines was introduced in the second induction and all consolidation therapies to minimize total doses of anthracycline. The 3-year event-free (EFS) and overall survival rates for 43 eligible children were 83·6% [95% confidence interval (CI): 68·6-91·8%] and 90·7% (95% CI: 77·1-96·4%), respectively. Although two patients died of intracranial haemorrhage or infection during induction phases, no cardiac adverse events or treatment-related deaths were observed during subsequent phases. Patients not displaying M1 marrow after the first induction therapy, or those under 5 years of age at diagnosis, showed inferior outcomes (3-year EFS rate; 33·3% (95% CI: 19·3-67·6%) and 54·6% (95% CI: 22·9-78·0%), respectively). In conclusion, a single administration of anthracycline during each consolidation phase was sufficient for treating childhood APL. In younger children, however, conventional ATRA and chemotherapy may be insufficient so that alternative therapies should be considered.

  6. Premature vascular damage in systemic lupus erythematosus.

    PubMed

    Kaplan, Mariana J

    2009-11-01

    Systemic lupus erythematosus (SLE) is a disease associated with a striking increase in the risk of premature cardiovascular (CV) complications due to accelerated atherosclerosis. Traditional CV risk factors seem to be less important predictors of CV events than the presence of active SLE. Immune dysregulation characteristic of lupus appears to play the dominant role in atherogenesis. While both SLE-specific and non-specific mechanisms have been proposed to play a prominent role in the induction of premature vascular damage in this disease, the exact etiology remains unclear. We have proposed that an imbalance between vascular damage and repair likely induced by Interferon- could play a prominent role in the induction of accelerated atherosclerosis in SLE. This review summarizes some of the proposed mechanisms that may promote accelerated vascular damage in lupus and explores potential targets for CV risk prevention in this patient population.

  7. Naproxen 500 mg bid versus acetaminophen 1000 mg qid: effect on swelling and other acute postoperative events after bilateral third molar surgery.

    PubMed

    Bjørnsson, G A; Haanaes, H R; Skoglund, L A

    2003-08-01

    A controlled, randomized, double-blind crossover study, in which the patients acted as their own controls, was carried out to test the efficacy of naproxen 500 mg x 2 versus acetaminophen 1000 mg x 4 for 3 days on the postoperative course following third molar surgery. Acetaminophen reduced the mean swelling on the 3rd postoperative day by 22.4% (p = 0.023) compared to that after naproxen. On the 6th postoperative day, there was 20.9% less mean swelling with naproxen (p = 0.44), although the total swelling measurements were much less than those measured on the 3rd postoperative day. Summed pain intensity (SUMPI3.5-11) on the day of surgery revealed no statistically significant difference between the acetaminophen or naproxen regimen with the exception of 0.5 hours (p = 0.002) and 1 hour (p = 0.009) after first medication when acetaminophen gave less pain than naproxen. Since the drug regimens were different, summed PI for the first acetaminophen dose interval (SUMPI3.5-6) and the first naproxen dose interval (SUMPI3.5-9) was calculated. There was a tendency toward a statistically significant difference in favor of acetaminophen for SUMPI3.5-6 (p = 0.055) but no statistically significant difference (p = 0.41) between the treatments with respect to SUMPI3.5-9. Naproxen was statistically superior (p < or = 0.002) to acetaminophen at 08:00, 12:00, and 16:00 hours on the 1st postoperative day and at 08:00 hours on the 2nd postoperative day, when the pain intensity level was lower than that on the day of surgery. A 3-day acetaminophen regimen reduces acute postoperative swelling better than naproxen on the 3rd postoperative day after third molar surgery but not on the 6th postoperative day when the total swelling is less. PMID:12953342

  8. Usefulness of Combining Galectin-3 and BIVA Assessments in Predicting Short- and Long-Term Events in Patients Admitted for Acute Heart Failure

    PubMed Central

    De Berardinis, Benedetta; Magrini, Laura; Zampini, Giorgio; Zancla, Benedetta; Salerno, Gerardo; Cardelli, Patrizia; Di Stasio, Enrico; Gaggin, Hanna K.; Belcher, Arianna; Parry, Blair A.; Nagurney, John T.; Januzzi, James L.; Di Somma, Salvatore

    2014-01-01

    Introduction. Acute heart failure (AHF) is associated with a higher risk for the occurrence of rehospitalization and death. Galectin-3 (GAL3) is elevated in AHF patients and is an indicator in predicting short-term mortality. The total body water using bioimpedance vector analysis (BIVA) is able to identify mortality within AHF patients. The aim of this study was to evaluate the short- and long-term predictive value of GAL3, BIVA, and the combination of both in AHF patients in Emergency Department (ED). Methods. 205 ED patients with AHF were evaluated by testing for B type natriuretic peptide (BNP) and GAL3. The primary endpoint was death and rehospitalization at 30, 60, 90, and 180 days and 12 and 18 months. AHF patients were evaluated at the moment of ED arrival with clinical judgment and GAL3 and BIVA measurement. Results. GAL3 level was significantly higher in patients >71 years old, and with eGFR < 30 cc/min. The area under the curve (AUC) of GAL3 + BIVA, GAL3 and BIVA for death and rehospitalization both when considered in total and when considered serially for the follow-up period showed that the combination has a better prognostic value. Kaplan-Meier survival curve for GAL3 values >17.8 ng/mL shows significant survival difference. At multivariate Cox regression analysis GAL3 is an independent variable to predict death + rehospitalization with a value of 32.24 ng/mL at 30 days (P < 0.005). Conclusion. In patients admitted for AHF an early assessment of GAL3 and BIVA seems to be useful in identifying patients at high risk for death and rehospitalization at short and long term. Combining the biomarker and the device could be of great utility since they monitor the severity of two pathophysiological different mechanisms: heart fibrosis and fluid overload. PMID:25101304

  9. 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

  10. [Vascular factors in dementia].

    PubMed

    Bidzan, Leszek

    2005-01-01

    Cerebrovascular factors are a common cause of dementia or contribute to cognitive decline in other dementias. Studies showing that cerebrovascular factors are the risk factors for neurodegenerative dementias, especially Alzheimer's disease. Practically all neurodegenerative dementias have a vascular component that reduces cerebral perfusion and has great impact on the clinical picture. Recent data support the view that the neurodegenerative process is caused by cerebrovascular mechanisms. The results showed that patients with vascular cognitive impairment have a typical clinical picture. Various important non-cognitive features are caused by cerebrovascular factors and are associated with a more rapid course of illness. On the other hand the term vascular diseases or cerebrovascular factors include a variety of vascular pathologies. PMID:16358596

  11. Vascular ring (image)

    MedlinePlus

    Vascular ring is a term used to describe a number of abnormal formations of the aorta, the large artery ... the pulmonary artery. The abnormal vessel(s) forms a ring, which encircles and may press down on the ...

  12. Heart and vascular services

    MedlinePlus

    ... scan of the heart Stress tests (many different types of stress tests exist) Vascular ultrasound, such as carotid ultrasound Venous ultrasound of the arms and legs SURGERIES AND INTERVENTIONS ... these types of procedures, a catheter is inserted through the ...

  13. Vascular Disease Foundation

    MedlinePlus

    ... or 911 immediately. @ 2016 Vascular Cures is a tax-exempt, nonprofit organization tax ID#: 94-2825216 as described in the Section ... 3) of the Internal Revenue Code. Donations are tax deductible. 555 Price Ave., Suite 180, Redwood City, ...

  14. Implications of Vascular Aging

    PubMed Central

    Barodka, Viachaslau M.; Joshi, Brijen L.; Berkowitz, Dan E.; Hogue, Charles W.; Nyhan, Daniel

    2011-01-01

    Chronological age is a well established risk factor for the development of cardiovascular diseases. The changes that accumulate in the vasculature with age, though, are highly variable. It is now increasingly recognized that indices of vascular health are more reliable than age per se in predicting adverse cardiovascular outcomes. The variation in the accrual of these age-related vascular changes is a function of multiple genetic and environmental factors. In this review, we highlight some of the pathophysiological mechanisms that characterize the vascular aging phenotype. Furthermore, we provide an overview of the key outcome studies that address the value of these vascular health indices in general and discuss potential effects on perioperative cardiovascular outcomes. PMID:21474663

  15. Sinuosities in vascular structures

    NASA Astrophysics Data System (ADS)

    Masson, J.-B.; Martin, J.-L.

    2007-12-01

    In most organs, depending on the scale, the nature of the heart pump, the geometry and topology of the organ, some of the blood vessels tend to exhibit sinuous trajectories. We describe a part of this sinuous behavior, including partial biological and strong physical effects in a global physical framework. We will voluntarily focus on physical and topological effects. This study is performed on the vitelline membrane of the chicken embryo. Crossing angles, sinuosity, and the oscillation amplitude of the vascular system are analyzed. Surprisingly, the equation of river meandering dynamics is found to model the sinuosities in the vascular system, and an extension of this equation to non planar case is able to explain the effect of tissue global curvature on the vascular system. Results of this study could lead to a new understanding of the interplay between biological signaling and physical effects in determining the vascular pattern in different tissues.

  16. What Is Vascular Disease?

    MedlinePlus

    ... or 911 immediately. @ 2016 Vascular Cures is a tax-exempt, nonprofit organization tax ID#: 94-2825216 as described in the Section ... 3) of the Internal Revenue Code. Donations are tax deductible. 555 Price Ave., Suite 180, Redwood City, ...

  17. Women and Vascular Disease

    MedlinePlus

    ... Search Patient information Membership Directory (SIR login) Interventional Radiology Women and Vascular Disease Early Warning Symptom for ... major public health issue, the Society of Interventional Radiology recommends greater screening efforts by the medical community ...

  18. Vascular structures in dermoscopy*

    PubMed Central

    Ayhan, Erhan; Ucmak, Derya; Akkurt, ZeynepMeltem

    2015-01-01

    Dermoscopy is an aiding method in the visualization of the epidermis and dermis. It is usually used to diagnose melanocytic lesions. In recent years, dermoscopy has increasingly been used to diagnose non-melanocytic lesions. Certain vascular structures, their patterns of arrangement and additional criteria may demonstrate lesion-specific characteristics. In this review, vascular structures and their arrangements are discussed separately in the light of conflicting views and an overview of recent literature. PMID:26375224

  19. Vascular Hyperpermeability and Aging

    PubMed Central

    Oakley, Ryan; Tharakan, Binu

    2014-01-01

    Vascular hyperpermeability, the excessive leakage of fluid and proteins from blood vessels to the interstitial space, commonly occurs in traumatic and ischemic injuries. This hyperpermeability causes tissue vasogenic edema, which often leads to multiple organ failure resulting in patient death. Vascular hyperpermeability occurs most readily in small blood vessels as their more delicate physical constitution makes them an easy target for barrier dysfunction. A single layer of endothelial cells, linked to one another by cell adhesion molecules, covers the interior surface of each blood vessel. The cell adhesion molecules play a key role in maintaining barrier functions like the regulation of permeability. Aging is a major risk factor for microvascular dysfunction and hyperpermeability. Apart from age-related remodeling of the vascular wall, endothelial barrier integrity and function declines with the advancement of age. Studies that address the physiological and molecular basis of vascular permeability regulation in aging are currently very limited. There have been many cellular and molecular mechanisms proposed to explain aging-related endothelial dysfunction but their true relationship to barrier dysfunction and hyperpermeability is not clearly known. Among the several mechanisms that promote vascular dysfunction and hyperpermeability, the following are considered major contributors: oxidative stress, inflammation, and the activation of apoptotic signaling pathways. In this review we highlighted (a) the physiological, cellular and molecular changes that occur in the vascular system as a product of aging; (b) the potential mechanisms by which aging leads to barrier dysfunction and vascular hyperpermeability in the peripheral and the blood-brain barrier; (c) the mechanisms by which the age-related increases in oxidative stress, inflammatory markers and apoptotic signaling etc. cause endothelial dysfunction and their relationship to hyperpermeability; and (d) the

  20. Assessing vascular dementia.

    PubMed

    Forette, F; Rigaud, A S; Morin, M; Gisselbrecht, M; Bert, P

    1995-10-01

    Vascular dementia is the most common cause of dementia in the elderly after Alzheimer's disease. Many forms of vascular dementia have been described: multi-infarct dementia, lacunar dementia, Binswanger's subcortical encephalopathy, cerebral amyloid angiopathy, white matter lesions associated with dementias, single infarct dementia, dementia linked to hypoperfusion and haemorrhagic dementia. The difficulty of diagnosing vascular dementia must not be underestimated and an international consensus is needed for epidemiological studies. The NINCDS-AIREN group has recently published diagnostic criteria. The State of California Alzheimer's Disease Diagnostic and Treatment Centers also proposed some which differ from the NINCDS-AIREN criteria in considering only ischaemic vascular dementia and not other mechanisms such as haemorrhagic or hypoxic lesions. Most studies stress hypertension as the most powerful risk factor for all forms of vascular dementia. The incidence rate ranges from 7 per 1000 person-years in normal volunteers to 16 per 1000 person-years in hypertensive patients. No therapeutic attempt has influenced the course of the disease once the dementing condition is established. The only effective approach is preventive treatment. The objective of the SYST-EUR Vascular Dementia project is to confirm that the treatment of isolated systolic hypertension is able to reduce its incidence.

  1. Acute Bronchitis

    MedlinePlus

    ... tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis get better within several days. But your ... that cause colds and the flu often cause acute bronchitis. These viruses spread through the air when ...

  2. [Vascular complications associated with lumbar spinal surgery].

    PubMed

    Riedemann-Wistuba, M; Alonso-Pérez, M; Llaneza-Coto, J M

    2016-01-01

    Although there are currently less invasive techniques available for the treatment of spinal injuries, open surgery is still required in many cases. Vascular injuries occurring during lumbar spine surgery, although uncommon, are of great importance due to their potential gravity. Clinical manifestations vary from an acute hemorrhagic shock that needs urgent treatment to save the patient's life, to insidious injuries or an asymptomatic evolution, and should be studied to choose the best therapeutic alternative. Four cases are reported that represent this range of possibilities and emphasize the importance of a careful surgical technique during lumbar spine interventions, and the need for high clinical suspicion, essential for the early diagnosis of these vascular complications. The current therapeutic options are also discussed. PMID:25662569

  3. [Vascular complications associated with lumbar spinal surgery].

    PubMed

    Riedemann-Wistuba, M; Alonso-Pérez, M; Llaneza-Coto, J M

    2016-01-01

    Although there are currently less invasive techniques available for the treatment of spinal injuries, open surgery is still required in many cases. Vascular injuries occurring during lumbar spine surgery, although uncommon, are of great importance due to their potential gravity. Clinical manifestations vary from an acute hemorrhagic shock that needs urgent treatment to save the patient's life, to insidious injuries or an asymptomatic evolution, and should be studied to choose the best therapeutic alternative. Four cases are reported that represent this range of possibilities and emphasize the importance of a careful surgical technique during lumbar spine interventions, and the need for high clinical suspicion, essential for the early diagnosis of these vascular complications. The current therapeutic options are also discussed.

  4. Antioxidants and vascular health.

    PubMed

    Bielli, Alessandra; Scioli, Maria Giovanna; Mazzaglia, Donatella; Doldo, Elena; Orlandi, Augusto

    2015-12-15

    Oxygen free radicals and other reactive oxygen species (ROS) are common products of normal aerobic cellular metabolism, but high levels of ROS lead to oxidative stress and cellular damage. Increased production of ROS favors vascular dysfunction, inducing altered vascular permeability and inflammation, accompanied by the loss of vascular modulatory function, the imbalance between vasorelaxation and vasoconstriction, and the aberrant expression of inflammatory adhesion molecules. Inflammatory stimuli promote oxidative stress generated from the increased activity of mitochondrial nicotinamide adenine dinucleotide phosphate oxidase, particularly of the Nox4 isoform, with the consequent impairment of mitochondrial β-oxidation. Vascular dysfunction due to the increase in Nox4 activity and ROS overproduction leads to the progression of cardiovascular diseases, diabetes, inflammatory bowel disease, and neurological disorders. Considerable research into the development of effective antioxidant therapies using natural derivatives or new synthetic molecules has been conducted. Antioxidants may prevent cellular damage by reducing ROS overproduction or interfering in reactions that involve ROS. Vitamin E and ascorbic acid are well known as natural antioxidants that counteract lipid peroxidative damage by scavenging oxygen-derived free radicals, thus restoring vascular function. Recently, preliminary studies on natural antioxidants such as goji berries, thymus, rosemary, green tea ginseng, and garlic have been conducted for their efficacy in preventing vascular damage. N-acetyl-cysteine and propionyl-L-carnitine are synthetic compounds that regulate ROS production by replacing endogenous antioxidants in both endothelial and smooth muscle cells. In this review, we consider the molecular mechanisms underlying the generation of oxidative stress-induced vascular dysfunction as well as the beneficial effects of antioxidant therapies.

  5. The long term prognosis in patients following thrombolysis for acute myocardial infarction: a view from a community hospital.

    PubMed

    Brophy, J M; Boulerice, M; Kerouac, M

    1996-08-01

    Thrombolysis in patients with acute myocardial infarction has been established to improve hospital survival. Less information is available about the long term evolution of unselected patients seen in community hospitals. Consequently, consecutive patients treated with thrombolysis for acute myocardial infarction and surviving until hospital discharge (n = 129) were followed for an average of 22 months. Mortality, recurrent ischemic events, coronary angiography and re-vascularizations were recorded for all patients. Two-year total and cardiovascular survival rates of 95 and 98% respectively were obtained with a conservative approach to early re-vascularization (n = 17, 13%). A history of prior myocardial infarction and early recurrent myocardial ischemia were significant predictors of increased cardiac events, while thallium stress testing provided no incremental value. Angiography and re-vascularizations were more frequently performed in younger patients (under 65 years old), anterior vs. inferior infarction and those with early residual ischemia. Women received less aggressive investigation and therapy then men and this may represent a gender bias, unmeasured residual confounding or the play of chance in a small sample size. Further studies are needed to confirm or refute these findings.

  6. Decoding dynamic Ca2+ signaling in the vascular endothelium

    PubMed Central

    Taylor, Mark S.; Francis, Michael

    2014-01-01

    Although acute and chronic vasoregulation is inherently driven by endothelial Ca2+, control and targeting of Ca2+-dependent signals are poorly understood. Recent studies have revealed localized and dynamic endothelial Ca2+ events comprising an intricate signaling network along the vascular intima. Discrete Ca2+ transients emerging from both internal stores and plasmalemmal cation channels couple to specific membrane K+ channels, promoting endothelial hyperpolarization and vasodilation. The spatiotemporal tuning of these signals, rather than global Ca2+ elevation, appear to direct endothelial functions under physiologic conditions. In fact, altered patterns of dynamic Ca2+ signaling may underlie essential endothelial dysfunction in a variety of cardiovascular diseases. Advances in imaging approaches and analyses in recent years have allowed for detailed detection, quantification, and evaluation of Ca2+ dynamics in intact endothelium. Here, we discuss recent insights into these signals, including their sources of origination and their functional encoding. We also address key aspects of data acquisition and interpretation, including broad applications of automated high-content analysis. PMID:25452732

  7. Vascular Response to Experimental Stent Malapposition and Under-Expansion.

    PubMed

    O'Brien, Caroline C; Lopes, Augusto C; Kolandaivelu, Kumaran; Kunio, Mie; Brown, Jonathan; Kolachalama, Vijaya B; Conway, Claire; Bailey, Lynn; Markham, Peter; Costa, Marco; Ware, James; Edelman, Elazer R

    2016-07-01

    Up to 80% of all endovascular stents have malapposed struts, and while some impose catastrophic events others are inconsequential. Thirteen stents were implanted in coronary arteries of seven healthy Yorkshire pigs, using specially-designed cuffed balloons inducing controlled stent malapposition and under-expansion. Optical coherence tomography (OCT) imaging confirmed that 25% of struts were malapposed (strut-wall distance acutely resolved (<1% of struts remained malapposed at day 5), with strong correlation between lumen and the stent cross-sectional areas (slope = 0.86, p < 0.0001, R (2) = 0.94). OCT in three of the most significantly malapposed vessels at baseline showed high correlation of elastic lamina area and lumen area (R (2) = 0.96) suggesting all lumen loss was related to contraction of elastic lamina with negligible plaque/intimal hyperplasia growth. Simulation showed this vascular recoil could be partially explained by the non-uniform strain environment created from sub-optimal expansion of device and balloon, and the inability of stent support in the malapposed region to resist recoil. Malapposition as a result of stent under-expansion is resolved acutely in healthy normal arteries, suggesting existing animal models are limited in replicating clinically observed persistent stent malapposition.

  8. Effects of mir-21 on Cardiac Microvascular Endothelial Cells After Acute Myocardial Infarction in Rats: Role of Phosphatase and Tensin Homolog (PTEN)/Vascular Endothelial Growth Factor (VEGF) Signal Pathway

    PubMed Central

    Yang, Feng; Liu, Wenwei; Yan, Xiaojuan; Zhou, Hanyun; Zhang, Hongshen; Liu, Jianfei; Yu, Ming; Zhu, Xiaoshan; Ma, Kezhong

    2016-01-01

    Background This study investigated how miR-21 expression is reflected in acute myocardial infarction and explored the role of miR-21 and the PTEN/VEGF signaling pathway in cardiac microvascular endothelial cells. Material/Methods We used an in vivo LAD rat model to simulate acute myocardial infarction. MiR-21 mimics and miR-21 inhibitors were injected and transfected into model rats in order to alter miR-21 expression. Cardiac functions were evaluated using echocardiographic measurement, ELISA, and Masson staining. In addition, lenti-PTEN and VEGF siRNA were transfected into CMEC cells using standard procedures for assessing the effect of PTEN and VEGE on cell proliferation, apoptosis, and angiogenesis. MiR-21, PTEN, and VEGF expressions were examined by RT-PCR and Western blot. The relationship between miR-21 and PTEN was determined by the luciferase activity assay. Results We demonstrated that miR-21 bonded with the 3′-UTR of PTEN and suppressed PTEN expressions. Established models significantly induced cardiac infarct volume and endothelial injury marker expressions as well as miR-21 and PTEN expressions (P<0.05). MiR-21 mimics exhibited significantly protective effects since they down-regulated both infarction size and injury marker expressions by increasing VEGF expression and inhibiting PTEN expression (P<0.05). In addition, results from in vitro research show that lenti-PTEN and VEGF siRNA can notably antagonize the effect of miR-21 on cell proliferation, apoptosis, and angiogenesis (P<0.05). Conclusions MiR-21 exerts protective effects on endothelial injury through the PTEN/VEGF pathway after acute myocardial infarction. PMID:27708252

  9. Determinants to optimize response to clopidogrel in acute coronary syndrome

    PubMed Central

    Giusti, Betti; Gori, Anna Maria; Marcucci, Rossella; Saracini, Claudia; Vestrini, Anna; Abbate, Rosanna

    2010-01-01

    The inhibition of platelet function by antiplatelet therapy determines the improvement of the survival of patients with clinically evident cardiovascular disease. Clopidogrel in combination with aspirin is the recommended standard of care for reducing the occurrence of cardiovascular events in patients with acute coronary syndromes undergoing percutaneous coronary intervention. However, major adverse cardiovascular events including stent thrombosis occur in patients taking clopidogrel and aspirin. A growing body of evidence demonstrates that high post-treatment platelet reactivity on antiplatelet treatment is associated with increased risk of adverse clinical events. Clopidogrel requires conversion to active metabolite by cytochrome P450 isoenzymes. The active metabolite inhibits ADP-stimulated platelet activation by irreversibly binding to P2Y12 receptors. Recently, the loss-of-function CYP2C19*2 allele has been associated with decreased metabolization of clopidogrel, poor antiaggregant effect, and increased cardiovascular events. In high risk vascular patients, the CYP2C19*2 polymorphism is a strong predictor of adverse cardiovascular events and particularly of stent thrombosis. Prospective studies evaluating if an antiplatelet treatment tailored on individual characteristics of patients, CYP2C19*2 genotypes, platelet phenotype, drug–drug interaction, as well as traditional and procedural risk factors, are now urgently needed for the identification of therapeutic strategies providing the best benefit for the single subject. PMID:23226041

  10. 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. PMID:24099797

  11. 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

  12. Acute cell death rate of vascular smooth muscle cells during or after short heating up to 20s ranging 50 to 60°C as a basic study of thermal angioplasty

    NASA Astrophysics Data System (ADS)

    Shinozuka, Machiko; Shimazaki, Natsumi; Ogawa, Emiyu; Machida, Naoki; Arai, Tsunenori

    2014-02-01

    We studied the relations between the time history of smooth muscle cells (SMCs) death rate and heating condition in vitro to clarify cell death mechanism in heating angioplasty, in particular under the condition in which intimal hyperplasia growth had been prevented in vivo swine experiment. A flow heating system on the microscope stage was used for the SMCs death rate measurement during or after the heating. The cells were loaded step-heating by heated flow using a heater equipped in a Photo-thermo dynamic balloon. The heating temperature was set to 37, 50-60°C. The SMCs death rate was calculated by a division of PI stained cell number by Hoechst33342 stained cell number. The SMCs death rate increased 5-10% linearly during 20 s with the heating. The SMCs death rate increased with duration up to 15 min after 5 s heating. Because fragmented nuclei were observed from approximately 5 min after the heating, we defined that acute necrosis and late necrosis were corresponded to within 5 min after the heating and over 5 min after the heating, respectively. This late necrosis is probably corresponding to apoptosis. The ratio of necrotic interaction divided the acute necrosis rate by the late necrosis was calculated based on this consideration as 1.3 under the particular condition in which intimal hyperplasia growth was prevented in vivo previous porcine experiment. We think that necrotic interaction rate is larger than expected rate to obtain intimal hyperplasia suppression.

  13. Acute Diagnosis and Management of Stroke Presenting Dizziness or Vertigo.

    PubMed

    Lee, Seung-Han; Kim, Ji-Soo

    2015-08-01

    Stroke involving the brainstem and cerebellum frequently presents acute vestibular syndrome. Although vascular vertigo is known to usually accompany other neurologic symptoms and signs, isolated vertigo from small infarcts involving the cerebellum or brainstem has been increasingly recognized. Bedside neuro-otologic examination can reliably differentiate acute vestibular syndrome due to stroke from more benign inner ear disease. Sometimes acute isolated audiovestibular loss may herald impending infarction in the territory of the anterior inferior cerebellar artery. Accurate identification of isolated vascular vertigo is very important because misdiagnosis of acute stroke may result in significant morbidity and mortality.

  14. Building Vascular Networks

    PubMed Central

    Bae, Hojae; Puranik, Amey S.; Gauvin, Robert; Edalat, Faramarz; Carrillo-Conde, Brenda; Peppas, Nicholas A.; Khademhosseini, Ali

    2013-01-01

    Only a few engineered tissues—skin, cartilage, bladder—have achieved clinical success, and biomaterials designed to replace more complex organs are still far from commercial availability. This gap exists in part because biomaterials lack a vascular network to transfer the oxygen and nutrients necessary for survival and integration after transplantation. Thus, generation of a functional vasculature is essential to the clinical success of engineered tissue constructs and remains a key challenge for regenerative medicine. In this Perspective, we discuss recent advances in vascularization of biomaterials through the use of biochemical modification, exogenous cells, or microengineering technology. PMID:23152325

  15. [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.

  16. Pilot Mouse Study of 1 mm Inner Diameter (ID) Vascular Graft Using Electrospun Poly(ester urea) Nanofibers.

    PubMed

    Gao, Yaohua; Yi, Tai; Shinoka, Toshiharu; Lee, Yong Ung; Reneker, Darrell H; Breuer, Christopher K; Becker, Matthew L

    2016-09-01

    An off-the-shelf, small diameter tissue engineered vascular graft (TEVG) would be transformative to surgeons in multiple subspecialties. Herein, the results of a small diameter (ID ≈ 1 mm) vascular graft constructed from resorbable, amino acid-based poly(ester urea) (PEU) are reported. Electrospun PEU grafts of two different wall thicknesses (type A: 250 μm; type B: 350 μm) are implanted as abdominal infra-renal aortic grafts in a severe combined immune deficient/beige mouse model and evaluated for vessel remodeling over one year. Significantly, the small diameter TEVG does not rupture or lead to acute thrombogenic events during the intervals tested. The pilot TEVG in vivo shows long-term patency and extensive tissue remodeling with type A grafts. Extensive tissue remodeling in type A grafts leads to the development of well-circumscribed neovessels with an endothelial inner lining, a neointima containing smooth muscle cells. However, due to slow degradation of the PEU scaffold materials in vivo, the grafts remain after one year. The type B grafts, which have 350 μm thick walls, experience occlusion over the one year interval due to intimal hyperplasia. This study affords significant findings that will guide the design of future generations of small diameter vascular grafts.

  17. Excretory/secretory antigens from Dirofilaria immitis adult worms interact with the host fibrinolytic system involving the vascular endothelium.

    PubMed

    González-Miguel, Javier; Morchón, Rodrigo; Mellado, Isabel; Carretón, Elena; Montoya-Alonso, José Alberto; Simón, Fernando

    2012-02-01

    Dirofilaria immitis is the causative agent of canine and feline heartworm disease. The parasite can survive for long periods of time (7 years or more) in the circulatory system of immunocompetent reservoirs, producing usually a chronic inflammatory vascular disease. In addition, the simultaneous death of groups of adult worms can trigger an acute disease characterized by the exacerbation of inflammatory reactions and the emergence of serious thromboembolic events. In the context of the D. immitis/host relationships, the aim of this study was to investigate the interaction between the excretory/secretory antigens from D. immitis adult worms (DiES) and the fibrinolytic system of the host. Using an enzyme-linked immunosorbent assay we showed that DiES extract is able to bind plasminogen and generate plasmin, although this fact requires the presence of the tissue plasminogen activator (t-PA). Moreover, we established that DiES extract enhances t-PA expression in cultured vascular endothelial cells. Additionally, 10 plasminogen-binding proteins from DiES extract were identified by mass spectrometry (HSP60, actin-1/3, actin, actin 4, transglutaminase, GAPDH, Ov87, LOAG_14743, galectin and P22U). The data suggest that DiES antigens interact with the environment of the parasite regulating the activation of the fibrinolytic system of the host with involvement of the vascular endothelium in the process.

  18. [Gastric vascular lesions in cirrhosis: gastropathy and antral vascular ectasia].

    PubMed

    Casas, Meritxell; Calvet, Xavier; Vergara, Mercedes; Bella, Maria Rosa; Junquera, Félix; Martinez-Bauer, Eva; Campo, Rafael

    2015-02-01

    Portal hypertensive gastropathy (GHP) is a complication of portal hypertension usually associated with liver cirrhosis. The pathogenesis is unclear but the presence of portal hypertension is an essential factor for its development. GHP may be asymptomatic or present as gastrointestinal bleeding or iron deficiency anemia. Endoscopic lesions vary from a mosaic pattern to diffuse red spots; the most common location is the fundus. Treatment is indicated when there is acute or chronic bleeding, as secondary prophylaxis. There is insufficient evidence to recommend primary prophylaxis in patients who have never bled. Drugs that decrease portal pressure, such as non-cardioselective beta-blockers, and/or endoscopic ablative treatments, such as argon-beam coagulation, may be used. The role of transarterial intrahepatic portosystemic shunt) or bypass surgery has been insufficiently analyzed. Antral vascular ectasia (EVA) is a rare entity in liver cirrhosis, whose pathophysiology is still unknown. Clinical presentation is similar to that of GHP and endoscopy usually shows red spots in the antrum. Biopsy is often required to differentiate EVA from GHP. There is no effective medical therapy, so endoscopic ablative therapy and, in severe cases, antrectomy are recommended.

  19. 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

  20. Vascular wall extracellular matrix proteins and vascular diseases

    PubMed Central

    Xu, Junyan; Shi, Guo-Ping

    2014-01-01

    Extracellular matrix proteins form the basic structure of blood vessels. Along with providing basic structural support to blood vessels, matrix proteins interact with different sets of vascular cells via cell surface integrin or non-integrin receptors. Such interactions induce vascular cell de novo synthesis of new matrix proteins during blood vessel development or remodeling. Under pathological conditions, vascular matrix proteins undergo proteolytic processing, yielding bioactive fragments to influence vascular wall matrix remodeling. Vascular cells also produce alternatively spliced variants that induce vascular cell production of different matrix proteins to interrupt matrix homeostasis, leading to increased blood vessel stiffness; vascular cell migration, proliferation, or death; or vascular wall leakage and rupture. Destruction of vascular matrix proteins leads to vascular cell or blood-borne leukocyte accumulation, proliferation, and neointima formation within the vascular wall; blood vessels prone to uncontrolled enlargement during blood flow diastole; tortuous vein development; and neovascularization from existing pathological tissue microvessels. Here we summarize discoveries related to blood vessel matrix proteins within the past decade from basic and clinical studies in humans and animals — from expression to cross-linking, assembly, and degradation under physiological and vascular pathological conditions, including atherosclerosis, aortic aneurysms, varicose veins, and hypertension. PMID:25045854

  1. Adhesion in vascular biology

    PubMed Central

    de Rooij, Johan

    2014-01-01

    The vasculature delivers vital support for all other tissues by supplying oxygen and nutrients for growth and by transporting the immune cells that protect and cure them. Therefore, the microvasculature developed a special barrier that is permissive for gasses like oxygen and carbon dioxide, while fluids are kept inside and pathogens are kept out. While maintaining this tight barrier, the vascular wall also allows immune cells to exit at sites of inflammation or damage, a process that is called transmigration. The endothelial cell layer that forms the inner lining of the vasculature is crucial for the vascular barrier function as well as the regulation of transmigration. Therefore, adhesions between vascular endothelial cells are both tight and dynamic and the mechanisms by which they are established, and the mechanisms by which they are controlled have been extensively studied over the past decades. Because of our fundamental strive to understand biology, but also because defects in vascular barrier control cause a variety of clinical problems and treatment strategies may evolve from our detailed understanding of its mechanisms. This special focus issue features a collection of articles that review key components of the development and control of the endothelial cell-cell junction that is central to endothelial barrier function. PMID:25422845

  2. Engineered Vascularized Muscle Flap.

    PubMed

    Egozi, Dana; Shandalov, Yulia; Freiman, Alina; Rosenfeld, Dekel; Ben-Shimol, David; Levenberg, Shulamit

    2016-01-01

    One of the main factors limiting the thickness of a tissue construct and its consequential viability and applicability in vivo, is the control of oxygen supply to the cell microenvironment, as passive diffusion is limited to a very thin layer. Although various materials have been described to restore the integrity of full-thickness defects of the abdominal wall, no material has yet proved to be optimal, due to low graft vascularization, tissue rejection, infection, or inadequate mechanical properties. This protocol describes a means of engineering a fully vascularized flap, with a thickness relevant for muscle tissue reconstruction. Cell-embedded poly L-lactic acid/poly lactic-co-glycolic acid constructs are implanted around the mouse femoral artery and vein and maintained in vivo for a period of one or two weeks. The vascularized graft is then transferred as a flap towards a full thickness defect made in the abdomen. This technique replaces the need for autologous tissue sacrifications and may enable the use of in vitro engineered vascularized flaps in many surgical applications. PMID:26779840

  3. Dual antiplatelet therapy in acute coronary syndromes and coronary artery interventions.

    PubMed

    Sathyamurthy, I; Jayanthi, K

    2014-07-01

    Optimization of platelet inhibition in patients with acute coronary syndromes reduces the risk for ischemic events, but at the same time increases the risk for bleeding. There are several predictors of bleeding risk in patients with acute coronary syndromes. These include demographic variables such as advanced age, female gender, low body weight, concomitant diseases such as diabetes,renal insufficiency, noncardiac vascular disease such as cerebral vascular disease and a history of bleeding. It also includes the type of acute coronary syndromes such as patients presenting with ST segment elevation myocardial infarction, high killip class and low blood pressure. The diabetic population contains a higher proportion of patients who do not respond to antiplatelet drugs as expected and who also have more activated platelets that deserve very vigorous inhibition. The importance of dual antiplatelet therapy in patients undergoing balloon angioplasty and stenting is much discussed. Yet there are some questions which are to be answered clearly such as the following:- 1) In the need to balance the benefit of clot prevention with bleeding risk, is it better to continue dual antiplatelet therapy for longer than one year? 2) If so, is this benefit specific to drug eluting stents or to a more general population of stent patients? 3) Is the benefit mediated by prevention of stent thrombosis or is there a global reduction in cardiovascular risk? This review is to understand all these aspects and help a physician use antiplatelet drugs appropriately in day to day clinical practice for better patient outcomes. PMID:25672032

  4. 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

  5. [Diabetes mellitus and aging as a risk factor for cerebral vascular disease: epidemiology, pathophysiology and prevention].

    PubMed

    Cantú-Brito, Carlos; Mimenza-Alvarado, Alberto; Sánchez-Hernández, Juan José

    2010-01-01

    Older patients with diabetes have a high risk of vascular complications. They have an increase of approximately 3 times for developing stroke compared with subjects without diabetes. In addition, up to 75-80% of deaths in diabetic patients are associated with major cardiovascular events including stroke. The risk of stroke is high within 5 years of diagnosis for type 2 diabetes is 9% (mortality 21%), that is more than doubles the rate for the general population. From observational registries in a collaborative stroke study in Mexico, we analyzed clinical data, risk factors, and outcome of 1182 diabetic patients with cerebral ischemia, with focus in elderly subjects. There was a high frequency of hyperglycemia during the acute phase of stroke: the median value was 140 mg/dL and 40% had values higher than 180 mg/dL. Clinical outcome was usually unfavorable in elderly stroke patients with diabetes: case fatality rate was 30% at 30 days and survivors had moderate to severe disability, usually as consequence of the propensity to develop more systemic medical complications during hospital stay. Primary stroke prevention studies in patients with diabetes reveal that tight control of glucose is not associated with reduction in stroke risk. Therefore, proper control of other vascular risk factors is mandatory in patients with diabetes, in particular of arterial hypertension.

  6. [Diabetes mellitus and aging as a risk factor for cerebral vascular disease: epidemiology, pathophysiology and prevention].

    PubMed

    Cantú-Brito, Carlos; Mimenza-Alvarado, Alberto; Sánchez-Hernández, Juan José

    2010-01-01

    Older patients with diabetes have a high risk of vascular complications. They have an increase of approximately 3 times for developing stroke compared with subjects without diabetes. In addition, up to 75-80% of deaths in diabetic patients are associated with major cardiovascular events including stroke. The risk of stroke is high within 5 years of diagnosis for type 2 diabetes is 9% (mortality 21%), that is more than doubles the rate for the general population. From observational registries in a collaborative stroke study in Mexico, we analyzed clinical data, risk factors, and outcome of 1182 diabetic patients with cerebral ischemia, with focus in elderly subjects. There was a high frequency of hyperglycemia during the acute phase of stroke: the median value was 140 mg/dL and 40% had values higher than 180 mg/dL. Clinical outcome was usually unfavorable in elderly stroke patients with diabetes: case fatality rate was 30% at 30 days and survivors had moderate to severe disability, usually as consequence of the propensity to develop more systemic medical complications during hospital stay. Primary stroke prevention studies in patients with diabetes reveal that tight control of glucose is not associated with reduction in stroke risk. Therefore, proper control of other vascular risk factors is mandatory in patients with diabetes, in particular of arterial hypertension. PMID:21222313

  7. 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.

  8. Acute Systemic Infection with Dengue Virus Leads to Vascular Leakage and Death through Tumor Necrosis Factor-α and Tie2/Angiopoietin Signaling in Mice Lacking Type I and II Interferon Receptors.

    PubMed

    Phanthanawiboon, Supranee; Limkittikul, Kriengsak; Sakai, Yusuke; Takakura, Nobuyuki; Saijo, Masayuki; Kurosu, Takeshi

    2016-01-01

    Severe dengue is caused by host responses to viral infection, but the pathogenesis remains unknown. This is, in part, due to the lack of suitable animal models. Here, we report a non-mouse-adapted low-passage DENV-3 clinical isolate, DV3P12/08, derived from recently infected patients. DV3P12/08 caused a lethal systemic infection in type I and II IFN receptor KO mice (IFN-α/β/γR KO mice), which have the C57/BL6 background. Infection with DV3P12/08 induced a cytokine storm, resulting in severe vascular leakage (mainly in the liver, kidney and intestine) and organ damage, leading to extensive hemorrhage and rapid death. DV3P12/08 infection triggered the release of large amounts of TNF-α, IL-6, and MCP-1. Treatment with a neutralizing anti-TNF-α antibody (Ab) extended survival and reduced liver damage without affecting virus production. Anti-IL-6 neutralizing Ab partly prolonged mouse survival. The anti-TNF-α Ab suppressed IL-6, MCP-1, and IFN-γ levels, suggesting that the severe response to infection was triggered by TNF-α. High levels of TNF-α mRNA were expressed in the liver and kidneys, but not in the small intestine, of infected mice. Conversely, high levels of IL-6 mRNA were expressed in the intestine. Importantly, treatment with Angiopoietin-1, which is known to stabilize blood vessels, prolonged the survival of DV3P12/08-infected mice. Taken together, the results suggest that an increased level of TNF-α together with concomitant upregulation of Tie2/Angiopoietin signaling have critical roles in severe dengue infection. PMID:26844767

  9. Acute Systemic Infection with Dengue Virus Leads to Vascular Leakage and Death through Tumor Necrosis Factor-α and Tie2/Angiopoietin Signaling in Mice Lacking Type I and II Interferon Receptors

    PubMed Central

    Limkittikul, Kriengsak; Sakai, Yusuke; Takakura, Nobuyuki; Saijo, Masayuki

    2016-01-01

    Severe dengue is caused by host responses to viral infection, but the pathogenesis remains unknown. This is, in part, due to the lack of suitable animal models. Here, we report a non-mouse-adapted low-passage DENV-3 clinical isolate, DV3P12/08, derived from recently infected patients. DV3P12/08 caused a lethal systemic infection in type I and II IFN receptor KO mice (IFN-α/β/γR KO mice), which have the C57/BL6 background. Infection with DV3P12/08 induced a cytokine storm, resulting in severe vascular leakage (mainly in the liver, kidney and intestine) and organ damage, leading to extensive hemorrhage and rapid death. DV3P12/08 infection triggered the release of large amounts of TNF-α, IL-6, and MCP-1. Treatment with a neutralizing anti-TNF-α antibody (Ab) extended survival and reduced liver damage without affecting virus production. Anti-IL-6 neutralizing Ab partly prolonged mouse survival. The anti-TNF-α Ab suppressed IL-6, MCP-1, and IFN-γ levels, suggesting that the severe response to infection was triggered by TNF-α. High levels of TNF-α mRNA were expressed in the liver and kidneys, but not in the small intestine, of infected mice. Conversely, high levels of IL-6 mRNA were expressed in the intestine. Importantly, treatment with Angiopoietin-1, which is known to stabilize blood vessels, prolonged the survival of DV3P12/08-infected mice. Taken together, the results suggest that an increased level of TNF-α together with concomitant upregulation of Tie2/Angiopoietin signaling have critical roles in severe dengue infection. PMID:26844767

  10. Acute Systemic Infection with Dengue Virus Leads to Vascular Leakage and Death through Tumor Necrosis Factor-α and Tie2/Angiopoietin Signaling in Mice Lacking Type I and II Interferon Receptors.

    PubMed

    Phanthanawiboon, Supranee; Limkittikul, Kriengsak; Sakai, Yusuke; Takakura, Nobuyuki; Saijo, Masayuki; Kurosu, Takeshi

    2016-01-01

    Severe dengue is caused by host responses to viral infection, but the pathogenesis remains unknown. This is, in part, due to the lack of suitable animal models. Here, we report a non-mouse-adapted low-passage DENV-3 clinical isolate, DV3P12/08, derived from recently infected patients. DV3P12/08 caused a lethal systemic infection in type I and II IFN receptor KO mice (IFN-α/β/γR KO mice), which have the C57/BL6 background. Infection with DV3P12/08 induced a cytokine storm, resulting in severe vascular leakage (mainly in the liver, kidney and intestine) and organ damage, leading to extensive hemorrhage and rapid death. DV3P12/08 infection triggered the release of large amounts of TNF-α, IL-6, and MCP-1. Treatment with a neutralizing anti-TNF-α antibody (Ab) extended survival and reduced liver damage without affecting virus production. Anti-IL-6 neutralizing Ab partly prolonged mouse survival. The anti-TNF-α Ab suppressed IL-6, MCP-1, and IFN-γ levels, suggesting that the severe response to infection was triggered by TNF-α. High levels of TNF-α mRNA were expressed in the liver and kidneys, but not in the small intestine, of infected mice. Conversely, high levels of IL-6 mRNA were expressed in the intestine. Importantly, treatment with Angiopoietin-1, which is known to stabilize blood vessels, prolonged the survival of DV3P12/08-infected mice. Taken together, the results suggest that an increased level of TNF-α together with concomitant upregulation of Tie2/Angiopoietin signaling have critical roles in severe dengue infection.

  11. 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.

  12. Vascular Anomalies and Airway Concerns

    PubMed Central

    Clarke, Caroline; Lee, Edward I.; Edmonds, Joseph

    2014-01-01

    Vascular anomalies, both tumors and malformations, can occur anywhere in the body, including the airway, often without any external manifestations. However, vascular anomalies involving the airway deserve special consideration as proper recognition and management can be lifesaving. In this article, the authors discuss vascular anomalies as they pertains to the airway, focusing on proper diagnosis, diagnostic modalities, and therapeutic options. PMID:25045336

  13. Rodent Models of Vascular Cognitive Impairment.

    PubMed

    Yang, Yi; Kimura-Ohba, Shihoko; Thompson, Jeffrey; Rosenberg, Gary A

    2016-10-01

    Vascular cognitive impairment dementia (VCID), which is an increasingly important cause of dementia in the elderly, lacks effective treatments. Many different types of vascular disease are included under the diagnosis of VCID, including large vessel disease with multiple strokes and small vessel disease with lacunar infarcts and white matter disease. Animal models have been developed to study the multiple forms of VCID. Because of its progressive course, small vessel disease (SVD) is thought to be the optimal form of VCID for treatment. One theory is that the pathophysiology involves hypoxic hypoperfusion resulting in injury to the white matter and neuronal death. Bilateral occlusion of the common carotid arteries (BCAO) in a normotensive rat, which reduces cerebral blood flow, induces hypoxia with white matter damage; this model has been used to test drugs to block the injury. Another model is the spontaneously hypertensive/stroke prone rat (SHR/SP). Hypertension leads to small vessel disease resulting in progressive damage to the white matter, cortex, and hippocampus. Bilateral carotid artery stenosis (BCAS) with coils or ameroid constrictors produces a slower development of changes than BCAO, avoiding the acute ischemia. A few studies have been done with the two-clip, two-vessel occlusion renal model for induction of hypertension. There are benefits and drawbacks to each of these models with the model selected depending on the type of vascular damage that is to be studied. This review describes the most commonly used models, and the drugs that have been used to reduce the damage. PMID:27498679

  14. Interactions of hormones with the vascular endothelium. Effects on the control of vascular tone.

    PubMed

    Pohl, U; Kaas, J

    1994-03-01

    Due to their anatomical location vascular endothelial cells are an obvious target for hormones which are transported by the bloodstream. Studies on cultured endothelial cells, isolated vessels and the intact organism revealed the existence of multiple interactions between endothelial cells and circulating hormones. Not only are endothelial cells involved in the clearance of some specific circulating hormones, but they also form a tight barrier for other hormones thus preventing or attenuating their direct effects on vascular smooth muscle. Endothelial cells are also involved in the production of circulating angiotensin II by the angiotensin converting enzyme. Probably the most significant effect of hormones in vascular control is the ability of many of them to modulate the release of vasoactive autacoids such as nitric oxide, prostaglandins and endothelin-1. Aside from acute stimulating effects on autacoid production, some hormones, particularly steroids, exert chronic effects on vasoactive-factor gene expression. Apparently, in the control of vascular tone, interactions between circulating hormones and the endothelium play a major role. However, the functional significance of these interactions, especially in pathophysiologic conditions remains to be determined. PMID:8185724

  15. Digital vascular imaging and selective renin sampling in evaluation of vascular anatomy in renal transplant recipients.

    PubMed Central

    Khoury, G A; Irving, J D; Farrington, K; Varghese, Z; Persaud, J W; Sweny, P; Moorhead, J F; Fernando, O N

    1983-01-01

    Sixty-five renal transplant recipients underwent digital vascular imaging of the graft and simultaneous selective venous sampling for plasma renin activity. Renal artery stenosis was found in seven patients but did not appear to be functionally important. Diffuse intrarenal arterial attenuation was found in seven patients and was associated with impaired graft function and perfusion; it may indicate chronic rejection. Lower pole hypoperfusion was found in nine patients without impaired graft function or perfusion; its clinical relevance is uncertain. Aneurysmal dilatation of the main renal artery was found in two patients. Severe hypertension was common in patients with these three major abnormalities, but a causal association between the abnormality and hypertension could rarely be inferred. It may be the abnormalities on digital vascular imaging, especially diffuse intrarenal arterial attenuation and lower pole hypoperfusion, are secondary to severe hypertension. Digital vascular imaging with simultaneous selective venous sampling for plasma renin activity is useful in evaluating the vascular anatomy of the grafted kidney and in assessing any abnormality found. The combined procedure was well tolerated by all patients with no complications and no incidence of acute tubular dysfunction or proteinuria after the investigation. Images p1005-a PMID:6403169

  16. Abnormalities of vascular structure and function in pediatric hypertension.

    PubMed

    Urbina, Elaine M

    2016-07-01

    Hypertension is associated with adverse cardiovascular (CV) events in adults. Measures of vascular structure and function, including increased carotid intima-media thickness (cIMT) and elevated arterial stiffness predict hard CV events in adulthood. Newer data suggest that abnormalities in target organ damage are occurring in adolescents and young adults with high blood pressure. In this review, we discuss the techniques for measuring vascular dysfunction in young people and the evidence linking blood pressure levels to this type of target organ damage.

  17. The Vascular Depression Hypothesis: Mechanisms Linking Vascular Disease with Depression

    PubMed Central

    Taylor, Warren D.; Aizenstein, Howard J.; Alexopoulos, George S.

    2013-01-01

    The ‘Vascular Depression’ hypothesis posits that cerebrovascular disease may predispose, precipitate, or perpetuate some geriatric depressive syndromes. This hypothesis stimulated much research that has improved our understanding of the complex relationships between late-life depression (LLD), vascular risk factors, and cognition. Succinctly, there are well-established relationships between late-life depression, vascular risk factors, and cerebral hyperintensities, the radiological hallmark of vascular depression. Cognitive dysfunction is common in late-life depression, particularly executive dysfunction, a finding predictive of poor antidepressant response. Over time, progression of hyperintensities and cognitive deficits predicts a poor course of depression and may reflect underlying worsening of vascular disease. This work laid the foundation for examining the mechanisms by which vascular disease influences brain circuits and influences the development and course of depression. We review data testing the vascular depression hypothesis with a focus on identifying potential underlying vascular mechanisms. We propose a disconnection hypothesis, wherein focal vascular damage and white matter lesion location is a crucial factor influencing neural connectivity that contributes to clinical symptomatology. We also propose inflammatory and hypoperfusion hypotheses, concepts that link underlying vascular processes with adverse effects on brain function that influence the development of depression. Testing such hypotheses will not only inform the relationship between vascular disease and depression but also provide guidance on the potential repurposing of pharmacological agents that may improve late-life depression outcomes. PMID:23439482

  18. The pathophysiology of hypertensive acute heart failure.

    PubMed

    Viau, David M; Sala-Mercado, Javier A; Spranger, Marty D; O'Leary, Donal S; Levy, Phillip D

    2015-12-01

    While acute heart failure (AHF) is often regarded as a single disorder, an evolving understanding recognises the existence of multiple phenotypes with varied pathophysiological alterations. Herein we discuss hypertensive AHF and provide insight into a mechanism where acute fluid redistribution is caused by a disturbance in the ventricular-vascular coupling relationship. In this relationship, acute alterations in vascular elasticity, vasoconstriction and reflected pulse waves lead to increases in cardiac work and contribute to decompensated LV function with associated subendocardial ischaemia and end-organ damage. Chronic predisposing factors (neurohormonal activity, nitric oxide insensitivity, arterial stiffening) and physiological stressors (sympathetic surge, volume overload, physical exertion) that are causally linked to acute symptom onset are discussed. Lastly, we review treatment options including both nitrovasodilators and promising novel therapeutics, and discuss future directions in the management of this phenotypic variant.

  19. Vascular cognitive impairment and dementia.

    PubMed

    Gorelick, Philip B; Counts, Scott E; Nyenhuis, David

    2016-05-01

    Vascular contributions to cognitive impairment are receiving heightened attention as potentially modifiable factors for dementias of later life. These factors have now been linked not only to vascular cognitive disorders but also Alzheimer's disease. In this chapter we review 3 related topics that address vascular contributions to cognitive impairment: 1. vascular pathogenesis and mechanisms; 2. neuropsychological and neuroimaging phenotypic manifestations of cerebrovascular disease; and 3. prospects for prevention of cognitive impairment of later life based on cardiovascular and stroke risk modification. 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. PMID:26704177

  20. Plant Vascular Biology 2010

    SciTech Connect

    Ding, Biao

    2014-11-17

    This grant supported the Second International Conference on Plant Vascular Biology (PVB 2010) held July 24-28, 2010 on the campus of Ohio State University, Columbus, Ohio. Biao Ding (Ohio State University; OSU) and David Hannapel (Iowa State University; ISU) served as co-chairs of this conference. Biao Ding served as the local organizer. PVB is defined broadly here to include studies on the biogenesis, structure and function of transport systems in plants, under conditions of normal plant growth and development as well as of plant interactions with pathogens. The transport systems cover broadly the xylem, phloem, plasmodesmata and vascular cell membranes. The PVB concept has emerged in recent years to emphasize the integrative nature of the transport systems and approaches to investigate them.

  1. [Vascular variability syndromes].

    PubMed

    Otsuka, Kuniaki; Okajima, Kiyotaka; Yamanaka, Takashi; Cornelissen, Germaine

    2014-08-01

    Analytical global and local methods applied to human blood pressure (BP) records of around-the-clock measurements. The chronobiological interpretation of ambulatory BP monitoring records in the light of time-specified reference values derived from healthy peers matched by sex and age identify vascular variability disorders (VVDs) for an assessment of cardio-, cerebro-, and renovascular disease risk. VVD includes circadian BP over-swinging (CHAT, short for circadian hyper-amplitude tension), deficient heart rate variability, MESOR (midline-estimating statistic of rhythm) hypertension, excessively elevated pulse pressure over 60 mmHg, BP ecphasia (an odd timing of the circadian rhythms in BP but not in that of heart rate) and frequency alteration. The term MESOR-hypertension indicates only one of several VVDs that can combine to for sets of 2, 3 and n-component vascular variability syndromes. PMID:25167758

  2. [Vascular endothelial Barrier Function].

    PubMed

    Ivanov, A N; Puchinyan, D M; Norkin, I A

    2015-01-01

    Endothelium is an important regulator of selective permeability of the vascular wall for different molecules and cells. This review summarizes current data on endothelial barrier function. Endothelial glycocalyx structure, its function and role in the molecular transport and leukocytes migration across the endothelial barrier are discussed. The mechanisms of transcellular transport of macromolecules and cell migration through endothelial cells are reviewed. Special section of this article addresses the structure and function of tight and adherens endothelial junction, as well as their importance for the regulation of paracellular transport across the endothelial barrier. Particular attention is paid to the signaling mechanism of endothelial barrier function regulation and the factors that influence on the vascular permeability.

  3. Vascular Cambium Development

    PubMed Central

    Nieminen, Kaisa; Blomster, Tiina; Helariutta, Ykä; Mähönen, Ari Pekka

    2015-01-01

    Secondary phloem and xylem tissues are produced through the activity of vascular cambium, the cylindrical secondary meristem which arises among the primary plant tissues. Most dicotyledonous species undergo secondary development, among them Arabidopsis. Despite its small size and herbaceous nature, Arabidopsis displays prominent secondary growth in several organs, including the root, hypocotyl and shoot. Together with the vast genetic resources and molecular research methods available for it, this has made Arabidopsis a versatile and accessible model organism for studying cambial development and wood formation. In this review, we discuss and compare the development and function of the vascular cambium in the Arabidopsis root, hypocotyl, and shoot. We describe the current understanding of the molecular regulation of vascular cambium and compare it to the function of primary meristems. We conclude with a look at the future prospects of cambium research, including opportunities provided by phenotyping and modelling approaches, complemented by studies of natural variation and comparative genetic studies in perennial and woody plant species. PMID:26078728

  4. Congenital Vascular Anomalies.

    PubMed

    Gravereaux, Edwin C.; Nguyen, Louis L.; Cunningham, Leslie D.

    2004-04-01

    Congenital vascular anomalies are rare. The cardiovascular specialist should nevertheless be aware of the more common types of vascular anomalies and understand the implications for patient treatment and the likelihood of associated morbidity. The presentation of congenital arteriovenous malformations can range from asymptomatic or cosmetic lesions, to those causing ischemia, ulceration, hemorrhage, or high-output congestive heart failure. Treatment of large, symptomatic arteriovenous malformations often requires catheter-directed embolization prior to the attempt at complete surgical excision. Later recurrence, due to collateral recruitment, is frequent. Graded compression stockings and leg elevation are the mainstays of treatment for the predominantly venous congenital vascular anomalies. Most congenital central venous disorders are clinically silent. An exception is the retrocaval ureter. Retroaortic left renal vein, circumaortic venous ring, and absent, left-sided or duplicated inferior vena cava are relevant when aortic or inferior vena cava procedures are planned. The treatment of the venous disorders is directed at prevention or management of symptoms. Persistent sciatic artery, popliteal entrapment syndrome, and aberrant right subclavian artery origin are congenital anomalies that are typically symptomatic at presentation. Because they mimic more common diseases, diagnosis is frequently delayed. Delay can result in significant morbidity for the patient. Failure to make the diagnosis of persistent sciatic artery and popliteal entrapment can result in critical limb ischemia and subsequent amputation. Unrecognized aberrant right subclavian artery origin associated with aneurysmal degeneration can rupture and result in death. The treatment options for large-vessel arterial anomalies are surgical, sometimes in combination with endovascular techniques.

  5. [Three Patients with Acute Myocardial Infarction Associated with Targeted Therapy of Sorafenib for Metastatic Renal Cell Carcinoma : Case Report].

    PubMed

    Takagi, Kimiaki; Takai, Manabu; Kawata, Kei; Horie, Kengo; Kikuchi, Mina; Kato, Taku; Mizutani, Kosuke; Seike, Kensaku; Tsuchiya, Tomohiro; Yasuda, Mitsuru; Yokoi, Shigeaki; Nakano, Masahiro; Ushikoshi, Hiroaki; Miyazaki, Tatsuhiko; Deguchi, Takashi

    2015-09-01

    Sorafenib is a tyrosine kinase inhibitor (TKI) of the vascular endothelial growth factor receptor (VEGFR) used for advanced renal cell carcinoma. Treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal cell carcinoma. However, in spite of its therapeutic efficacy, sorafenib causes a wide range of adverse events. Cardiovascular adverse events have been observed when sorafenib was used with targeted agents. Although these adverse events like hypertension, reduced left ventricular ejection fraction, cardiac ischemia or infarction were manageable with standard medical therapies in most cases, some had a poor clinical outcome. We report three cases of acute myocardial infarction associated with sorafenib in patients with metastatic renal cell carcinoma. PMID:26497860

  6. [Three Patients with Acute Myocardial Infarction Associated with Targeted Therapy of Sorafenib for Metastatic Renal Cell Carcinoma : Case Report].

    PubMed

    Takagi, Kimiaki; Takai, Manabu; Kawata, Kei; Horie, Kengo; Kikuchi, Mina; Kato, Taku; Mizutani, Kosuke; Seike, Kensaku; Tsuchiya, Tomohiro; Yasuda, Mitsuru; Yokoi, Shigeaki; Nakano, Masahiro; Ushikoshi, Hiroaki; Miyazaki, Tatsuhiko; Deguchi, Takashi

    2015-09-01

    Sorafenib is a tyrosine kinase inhibitor (TKI) of the vascular endothelial growth factor receptor (VEGFR) used for advanced renal cell carcinoma. Treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal cell carcinoma. However, in spite of its therapeutic efficacy, sorafenib causes a wide range of adverse events. Cardiovascular adverse events have been observed when sorafenib was used with targeted agents. Although these adverse events like hypertension, reduced left ventricular ejection fraction, cardiac ischemia or infarction were manageable with standard medical therapies in most cases, some had a poor clinical outcome. We report three cases of acute myocardial infarction associated with sorafenib in patients with metastatic renal cell carcinoma.

  7. Polarity, continuity, and alignment in plant vascular strands.

    PubMed

    Sawchuk, Megan G; Scarpella, Enrico

    2013-09-01

    Plant vascular cells are joined end to end along uninterrupted lines to connect shoot organs with roots; vascular strands are thus polar, continuous, and internally aligned. What controls the formation of vascular strands with these properties? The "auxin canalization hypothesis"-based on positive feedback between auxin flow through a cell and the cell's capacity for auxin transport-predicts the selection of continuous files of cells that transport auxin polarly, thus accounting for the polarity and continuity of vascular strands. By contrast, polar, continuous auxin transport-though required-is insufficient to promote internal alignment of vascular strands, implicating additional factors. The auxin canalization hypothesis was derived from the response of mature tissue to auxin application but is consistent with molecular and cellular events in embryo axis formation and shoot organ development. Objections to the hypothesis have been raised based on vascular organizations in callus tissue and shoot organs but seem unsupported by available evidence. Other objections call instead for further research; yet the inductive and orienting influence of auxin on continuous vascular differentiation remains unique.

  8. CD8 T Cell-Initiated Vascular Endothelial Growth Factor Expression Promotes Central Nervous System Vascular Permeability under Neuroinflammatory Conditions

    PubMed Central

    Suidan, Georgette L.; Dickerson, Jonathan W.; Chen, Yi; McDole, Jeremiah R.; Tripathi, Pulak; Pirko, Istvan; Seroogy, Kim B.; Johnson, Aaron J.

    2010-01-01

    Dysregulation of the blood-brain barrier (BBB) is a hallmark feature of numerous neurologic disorders as diverse as multiple sclerosis, stroke, epilepsy, viral hemorrhagic fevers, cerebral malaria, and acute hemorrhagic leukoencephalitis. CD8 T cells are one immune cell type that have been implicated in promoting vascular permeability in these conditions. Our laboratory has created a murine model of CD8 T cell-mediated CNS vascular permeability using a variation of the Theiler’s murine encephalomyelitis virus system traditionally used to study multiple sclerosis. Previously, we demonstrated that CD8 T cells have the capacity to initiate astrocyte activation, cerebral endothelial cell tight junction protein alterations and CNS vascular permeability through a perforin-dependent process. To address the downstream mechanism by which CD8 T cells promote BBB dysregulation, in this study, we assess the role of vascular endothelial growth factor (VEGF) expression in this model. We demonstrate that neuronal expression of VEGF is significantly upregulated prior to, and coinciding with, CNS vascular permeability. Phosphorylation of fetal liver kinase-1 is significantly increased early in this process indicating activation of this receptor. Specific inhibition of neuropilin-1 significantly reduced CNS vascular permeability and fetal liver kinase-1 activation, and preserved levels of the cerebral endothelial cell tight junction protein occludin. Our data demonstrate that CD8 T cells initiate neuronal expression of VEGF in the CNS under neuroinflammatory conditions, and that VEGF may be a viable therapeutic target in neurologic disease characterized by inflammation-induced BBB disruption. PMID:20008293

  9. Diurnal and twenty-four hour patterning of human diseases: cardiac, vascular, and respiratory diseases, conditions, and syndromes.

    PubMed

    Smolensky, Michael H; Portaluppi, Francesco; Manfredini, Roberto; Hermida, Ramon C; Tiseo, Ruana; Sackett-Lundeen, Linda L; Haus, Erhard L

    2015-06-01

    Various medical conditions, disorders, and syndromes exhibit predictable-in-time diurnal and 24 h patterning in the signs, symptoms, and grave nonfatal and fatal events, e.g., respiratory ones of viral and allergic rhinorrhea, reversible (asthma) and non-reversible (bronchitis and emphysema) chronic obstructive pulmonary disease, cystic fibrosis, high altitude pulmonary edema, and decompression sickness; cardiac ones of atrial premature beats and tachycardia, paroxysmal atrial fibrillation, 3rd degree atrial-ventricular block, paroxysmal supraventricular tachycardia, ventricular premature beats, ventricular tachyarrhythmia, symptomatic and non-symptomatic angina pectoris, Prinzmetal vasospastic variant angina, acute (non-fatal and fatal) incidents of myocardial infarction, sudden cardiac arrest, in-bed sudden death syndrome of type-1 diabetes, acute cardiogenic pulmonary edema, and heart failure; vascular and circulatory system ones of hypertension, acute orthostatic postprandial, micturition, and defecation hypotension/syncope, intermittent claudication, venous insufficiency, standing occupation leg edema, arterial and venous branch occlusion of the eye, menopausal hot flash, sickle cell syndrome, abdominal, aortic, and thoracic dissections, pulmonary thromboembolism, and deep venous thrombosis, and cerebrovascular transient ischemic attack and hemorrhagic and ischemic stroke. Knowledge of these temporal patterns not only helps guide patient care but research of their underlying endogenous mechanisms, i.e., circadian and others, and external triggers plus informs the development and application of effective chronopreventive and chronotherapeutic strategies. PMID:25129838

  10. Diurnal and twenty-four hour patterning of human diseases: cardiac, vascular, and respiratory diseases, conditions, and syndromes.

    PubMed

    Smolensky, Michael H; Portaluppi, Francesco; Manfredini, Roberto; Hermida, Ramon C; Tiseo, Ruana; Sackett-Lundeen, Linda L; Haus, Erhard L

    2015-06-01

    Various medical conditions, disorders, and syndromes exhibit predictable-in-time diurnal and 24 h patterning in the signs, symptoms, and grave nonfatal and fatal events, e.g., respiratory ones of viral and allergic rhinorrhea, reversible (asthma) and non-reversible (bronchitis and emphysema) chronic obstructive pulmonary disease, cystic fibrosis, high altitude pulmonary edema, and decompression sickness; cardiac ones of atrial premature beats and tachycardia, paroxysmal atrial fibrillation, 3rd degree atrial-ventricular block, paroxysmal supraventricular tachycardia, ventricular premature beats, ventricular tachyarrhythmia, symptomatic and non-symptomatic angina pectoris, Prinzmetal vasospastic variant angina, acute (non-fatal and fatal) incidents of myocardial infarction, sudden cardiac arrest, in-bed sudden death syndrome of type-1 diabetes, acute cardiogenic pulmonary edema, and heart failure; vascular and circulatory system ones of hypertension, acute orthostatic postprandial, micturition, and defecation hypotension/syncope, intermittent claudication, venous insufficiency, standing occupation leg edema, arterial and venous branch occlusion of the eye, menopausal hot flash, sickle cell syndrome, abdominal, aortic, and thoracic dissections, pulmonary thromboembolism, and deep venous thrombosis, and cerebrovascular transient ischemic attack and hemorrhagic and ischemic stroke. Knowledge of these temporal patterns not only helps guide patient care but research of their underlying endogenous mechanisms, i.e., circadian and others, and external triggers plus informs the development and application of effective chronopreventive and chronotherapeutic strategies.

  11. Acute Intraoperative Pulmonary Aspiration

    PubMed Central

    Nason, Katie S.

    2015-01-01

    Synopsis Acute intraoperative aspiration is a potentially fatal complication with significant associated morbidity. Patients undergoing thoracic surgery are at increased risk for anesthesia-related aspiration, largely due to the predisposing conditions associated with this complication. Awareness of the risk factors, predisposing conditions, maneuvers to decrease risk and immediate management options by both the thoracic surgeon and the anesthesia team is imperative to reducing risk and optimizing patient outcomes associated with acute intraoperative pulmonary aspiration. Based on the root-cause analyses that many of the aspiration events can be traced back to provider factors, having an experienced anesthesiologist present for high-risk cases is also critical. PMID:26210926

  12. Vascular comorbidities in the onset and progression of multiple sclerosis.

    PubMed

    Tettey, Prudence; Simpson, Steve; Taylor, Bruce V; van der Mei, Ingrid A F

    2014-12-15

    Vascular comorbidities are common in the general population and are associated with adverse health outcomes. In people with multiple sclerosis (MS), an increasing amount of evidence suggests that vascular comorbidities are also common, but an association with MS risk and disability has not been conclusively established. This review aims to critically examine published data on the relationship between vascular comorbidities (including vascular risk factors) and MS. The evidence suggests an increased risk of MS in people with a high BMI during childhood or adolescence but not adulthood. People with established MS appear to have a slightly increased risk of cardiovascular disease and a greater proportion of people with MS die from cardiovascular disease, which has important implications for clinicians trying to identify risk factors for cardiovascular disease and reviewing treatment options. In relation to whether vascular comorbidities influence MS clinical disability or other aspects of the disease course, the key finding was that having type-2-diabetes, hypertension, dyslipidaemia or peripheral vascular disease at any point in the disease course may be associated with a greater progression in disability. Additionally, a negative effect of high cholesterol and triglycerides and a positive effect of higher HDL (high density lipoprotein) levels on acute inflammatory activity were observed on magnetic resonance imaging. The results of the published clinical trials of statins as an intervention in MS were however conflicting and care needs to be taken when treating people with MS with statins. Taken together, the literature seems to indicate a potential association of vascular comorbidities with MS risk and disability, but the number of prospective studies was sparse, thus precluding ascription of causality. We therefore recommend that future studies of the frequency and effects of vascular comorbidities on MS risk and disability should be prospective and objective

  13. The vascular system as a target of metal toxicity.

    PubMed

    Prozialeck, Walter C; Edwards, Joshua R; Nebert, Daniel W; Woods, James M; Barchowsky, Aaron; Atchison, William D

    2008-04-01

    Vascular system function involves complex interactions among the vascular endothelium, smooth muscle, the immune system, and the nervous system. The toxic metals cadmium (Cd), arsenic (As), and lead (Pb) can target the vascular system in a variety of ways, ranging from hemorrhagic injury to subtle pathogenic remodeling and metabolic changes. Acute Cd exposure results in hemorrhagic injury to the testis, although some strains of animals are resistant to this effect. A comparison of Cd-sensitive with Cd-resistant mouse strains showed that expression of the Slc39a8 gene, encoding the ZIP8 transporter, in the testis vasculature endothelium is responsible for this difference. Endogenously, ZIP8 is a Mn(2+)/HCO(3)(-)symporter that may also contribute to Cd damage in the kidney. Chronic Cd exposure is associated with various cardiovascular disorders such as hypertension and cardiomyopathy and it is reported to have both carcinogenic and anticarcinogenic activities. At noncytotoxic concentrations of 10-100nM, Cd can inhibit chemotaxis and tube formation of vascular endothelial cells. These angiostatic effects may be mediated through disruption of vascular endothelial cadherin, a Ca(2+)-dependent cell adhesion molecule. With regard to As, ingestion of water containing disease-promoting concentrations of As promotes capillarization of the liver sinusoidal endothelium. Because capillarization is a hallmark precursor for liver fibrosis and contributes to an imbalance of lipid metabolism, this As effect on hepatic endothelial cells may be a pathogenic mechanism underlying As-related vascular diseases. With regard to Pb, perinatal exposure may cause sustained elevations in adult blood pressure, and genetically susceptible animals may show enhanced sensitivity to this effect. Taken together, these data indicate that the vascular system is a critical target of metal toxicity and that actions of metals on the vascular system may play important roles in mediating the

  14. The Vascular System as a Target of Metal Toxicity

    PubMed Central

    Prozialeck, Walter C.; Edwards, Joshua R.; Nebert, Daniel W.; Woods, James M.; Barchowsky, Aaron; Atchison, William D.

    2009-01-01

    Vascular system function involves complex interactions among the vascular endothelium, smooth muscle, the immune system, and the nervous system. The toxic metals cadmium (Cd), arsenic (As), and lead (Pb) can target the vascular system in a variety of ways, ranging from hemorrhagic injury to subtle pathogenic remodeling and metabolic changes. Acute Cd exposure results in hemorrhagic injury to the testis, although some strains of animals are resistant to this effect. A comparison of Cd-sensitive with Cd-resistant mouse strains showed that expression of the Slc39a8 gene, encoding the ZIP8 transporter, in the testis vasculature endothelium is responsible for this difference. Endogenously, ZIP8 is a Mn2+/HCO3−symporter that may also contribute to Cd damage in the kidney. Chronic Cd exposure is associated with various cardiovascular disorders such as hypertension and cardiomyopathy and it is reported to have both carcinogenic and anticarcinogenic activities. At noncytotoxic concentrations of 10–100nM, Cd can inhibit chemotaxis and tube formation of vascular endothelial cells. These angiostatic effects may be mediated through disruption of vascular endothelial cadherin, a Ca2+-dependent cell adhesion molecule. With regard to As, ingestion of water containing disease-promoting concentrations of As promotes capillarization of the liver sinusoidal endothelium. Because capillarization is a hallmark precursor for liver fibrosis and contributes to an imbalance of lipid metabolism, this As effect on hepatic endothelial cells may be a pathogenic mechanism underlying As-related vascular diseases. With regard to Pb, perinatal exposure may cause sustained elevations in adult blood pressure, and genetically susceptible animals may show enhanced sensitivity to this effect. Taken together, these data indicate that the vascular system is a critical target of metal toxicity and that actions of metals on the vascular system may play important roles in mediating the pathophysiologic

  15. Role of Mitochondria in Cerebral Vascular Function: Energy Production, Cellular Protection, and Regulation of Vascular Tone.

    PubMed

    Busija, David W; Rutkai, Ibolya; Dutta, Somhrita; Katakam, Prasad V

    2016-06-13

    Mitochondria not only produce energy in the form of ATP to support the activities of cells comprising the neurovascular unit, but mitochondrial events, such as depolarization and/or ROS release, also initiate signaling events which protect the endothelium and neurons against lethal stresses via pre-/postconditioning as well as promote changes in cerebral vascular tone. Mitochondrial depolarization in vascular smooth muscle (VSM), via pharmacological activation of the ATP-dependent potassium channels on the inner mitochondrial membrane (mitoKATP channels), leads to vasorelaxation through generation of calcium sparks by the sarcoplasmic reticulum and subsequent downstream signaling mechanisms. Increased release of ROS by mitochondria has similar effects. Relaxation of VSM can also be indirectly achieved via actions of nitric oxide (NO) and other vasoactive agents produced by endothelium, perivascular and parenchymal nerves, and astroglia following mitochondrial activation. Additionally, NO production following mitochondrial activation is involved in neuronal preconditioning. Cerebral arteries from female rats have greater mitochondrial mass and respiration and enhanced cerebral arterial dilation to mitochondrial activators. Preexisting chronic conditions such as insulin resistance and/or diabetes impair mitoKATP channel relaxation of cerebral arteries and preconditioning. Surprisingly, mitoKATP channel function after transient ischemia appears to be retained in the endothelium of large cerebral arteries despite generalized cerebral vascular dysfunction. Thus, mitochondrial mechanisms may represent the elusive signaling link between metabolic rate and blood flow as well as mediators of vascular change according to physiological status. Mitochondrial mechanisms are an important, but underutilized target for improving vascular function and decreasing brain injury in stroke patients. © 2016 American Physiological Society. Compr Physiol 6:1529-1548, 2016.

  16. Role of Mitochondria in Cerebral Vascular Function: Energy Production, Cellular Protection, and Regulation of Vascular Tone.

    PubMed

    Busija, David W; Rutkai, Ibolya; Dutta, Somhrita; Katakam, Prasad V

    2016-01-01

    Mitochondria not only produce energy in the form of ATP to support the activities of cells comprising the neurovascular unit, but mitochondrial events, such as depolarization and/or ROS release, also initiate signaling events which protect the endothelium and neurons against lethal stresses via pre-/postconditioning as well as promote changes in cerebral vascular tone. Mitochondrial depolarization in vascular smooth muscle (VSM), via pharmacological activation of the ATP-dependent potassium channels on the inner mitochondrial membrane (mitoKATP channels), leads to vasorelaxation through generation of calcium sparks by the sarcoplasmic reticulum and subsequent downstream signaling mechanisms. Increased release of ROS by mitochondria has similar effects. Relaxation of VSM can also be indirectly achieved via actions of nitric oxide (NO) and other vasoactive agents produced by endothelium, perivascular and parenchymal nerves, and astroglia following mitochondrial activation. Additionally, NO production following mitochondrial activation is involved in neuronal preconditioning. Cerebral arteries from female rats have greater mitochondrial mass and respiration and enhanced cerebral arterial dilation to mitochondrial activators. Preexisting chronic conditions such as insulin resistance and/or diabetes impair mitoKATP channel relaxation of cerebral arteries and preconditioning. Surprisingly, mitoKATP channel function after transient ischemia appears to be retained in the endothelium of large cerebral arteries despite generalized cerebral vascular dysfunction. Thus, mitochondrial mechanisms may represent the elusive signaling link between metabolic rate and blood flow as well as mediators of vascular change according to physiological status. Mitochondrial mechanisms are an important, but underutilized target for improving vascular function and decreasing brain injury in stroke patients. © 2016 American Physiological Society. Compr Physiol 6:1529-1548, 2016. PMID:27347901

  17. Plant Phosphoglycerolipids: The Gatekeepers of Vascular Cell Differentiation.

    PubMed

    Gujas, Bojan; Rodriguez-Villalon, Antia

    2016-01-01

    In higher plants, the plant vascular system has evolved as an inter-organ communication network essential to deliver a wide range of signaling factors among distantly separated organs. To become conductive elements, phloem and xylem cells undergo a drastic differentiation program that involves the degradation of the majority of their organelles. While the molecular mechanisms regulating such complex process remain poorly understood, it is nowadays clear that phosphoglycerolipids display a pivotal role in the regulation of vascular tissue formation. In animal cells, this class of lipids is known to mediate acute responses as signal transducers and also act as constitutive signals that help defining organelle identity. Their rapid turnover, asymmetrical distribution across subcellular compartments as well as their ability to rearrange cytoskeleton fibers make phosphoglycerolipids excellent candidates to regulate complex morphogenetic processes such as vascular differentiation. Therefore, in this review we aim to summarize, emphasize and connect our current understanding about the involvement of phosphoglycerolipids in phloem and xylem differentiation.

  18. Plant Phosphoglycerolipids: The Gatekeepers of Vascular Cell Differentiation

    PubMed Central

    Gujas, Bojan; Rodriguez-Villalon, Antia

    2016-01-01

    In higher plants, the plant vascular system has evolved as an inter-organ communication network essential to deliver a wide range of signaling factors among distantly separated organs. To become conductive elements, phloem and xylem cells undergo a drastic differentiation program that involves the degradation of the majority of their organelles. While the molecular mechanisms regulating such complex process remain poorly understood, it is nowadays clear that phosphoglycerolipids display a pivotal role in the regulation of vascular tissue formation. In animal cells, this class of lipids is known to mediate acute responses as signal transducers and also act as constitutive signals that help defining organelle identity. Their rapid turnover, asymmetrical distribution across subcellular compartments as well as their ability to rearrange cytoskeleton fibers make phosphoglycerolipids excellent candidates to regulate complex morphogenetic processes such as vascular differentiation. Therefore, in this review we aim to summarize, emphasize and connect our current understanding about the involvement of phosphoglycerolipids in phloem and xylem differentiation. PMID:26904069

  19. Early histologic, metabolic, and vascular assessment of anterior cruciate ligament autografts

    SciTech Connect

    Kleiner, J.B.; Amiel, D.; Harwood, F.L.; Akeson, W.H.

    1989-01-01

    A rabbit model for anterior cruciate ligament (ACL) reconstruction using autogenous patellar tendon was utilized to study the early events of autograft cellular dynamics. Biochemical, autoradiographic, histological, and vascular injection techniques demonstrated that the native autograft cell population rapidly necroses. This repopulation occurs without a vascular contribution; cells entering the autograft are reliant upon synovial fluid nutrition.

  20. 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 ...

  1. Vascular effects of flavonoids.

    PubMed

    Almeida Rezende, Bruno; Pereira, Aline Carvalho; Cortes, Steyner F; Lemos, Virginia Soares

    2016-01-01

    Flavonoids are natural plant-derived polyphenolic compounds with various biological properties particularly in the cardiovascular system, including antiatherogenic, antioxidant, vasodilation, antihypertensive, and antiplatelet activities. These biological properties have been evaluated in several experimental and clinical studies. In addition, extensive reviews have discussed the antiatherogenic effect of these polyphenols. However, limited studies have investigated the potential therapeutic vascular effects of these compounds. This review brings together some recent studies, to establish the different signaling pathways involved in the molecular mechanisms that underlie the vasodilation induced by flavonoids.

  2. Potential vascular damage from radiation in the space environment

    NASA Astrophysics Data System (ADS)

    Griem, M. L.; Robotewskyj, A.; Nagel, R. H.

    1994-10-01

    Cultured endothelial cells of blood vessels have a Do of 2 Gy for X-rays. A dose of 0.5 Gy of X-rays has an acute effect on vessel diameter. The vessels may show other acute effects such as change in permeability including a change in the blood brain barrier. Changes occurring from late effects of chronic exposure in vascular architecture include telangiectasia and decrease in vascular density. Changes in the perivascular connective tissue particularly collagen may play a role in these changes. After charged particle exposure of 15 and 30 Gy, radiation changes in the blood brain barrier and vascular changes are noted in the nervous system. These long term changes are recorded by PET, MRI, and CT imaging. Chronic exposure to alpha particles causes vascular damage in compact bone resulting in bone infarcts. Using tandem scanning confocal microscopy in-situ imaging of the capillaries and collagen of the papillary dermis provides a non-invasive method of serial recording of changes in irradiated microvasculature.

  3. Medical management of vascular anomalies.

    PubMed

    Trenor, Cameron C

    2016-03-01

    We have entered an exciting era in the care of patients with vascular anomalies. These disorders require multidisciplinary care and coordination and dedicated centers have emerged to address this need. Vascular tumors have been treated with medical therapies for many years, while malformations have been historically treated with endovascular and operative procedures. The recent serendipitous discoveries of propranolol and sirolimus for vascular anomalies have revolutionized this field. In particular, sirolimus responses are challenging the dogma that vascular malformations are not biologically active. While initially explored for lymphatic anomalies, sirolimus is now being used broadly throughout the spectrum of vascular anomalies. Whether medical therapies are reserved for refractory patients or used first line is currently dependent on the experience and availability of alternative therapies at each institution. On the horizon, we anticipate new drugs targeting genes and pathways involved in vascular anomalies to be developed. Also, combinations of medications and protocols combining medical and procedural approaches are in development for refractory patients. PMID:27607327

  4. The pathobiology of vascular dementia

    PubMed Central

    Iadecola, Costantino

    2013-01-01

    Vascular cognitive impairment defines alterations in cognition, ranging from subtle deficits to full-blown dementia, attributable to cerebrovascular causes. Often coexisting with Alzheimer’s disease, mixed vascular and neurodegenerative dementia has emerged as the leading cause of age-related cognitive impairment. Central to the disease mechanism is the crucial role that cerebral blood vessels play in brain health, not only for the delivery of oxygen and nutrients, but also for the trophic signaling that links inextricably the well being of neurons and glia to that of cerebrovascular cells. This review will examine how vascular damage disrupts these vital homeostatic interactions, focusing on the hemispheric white matter, a region at heightened risk for vascular damage, and on the interplay between vascular factors and Alzheimer’s disease. Finally, preventative and therapeutic prospects will be examined, highlighting the importance of midlife vascular risk factor control in the prevention of late-life dementia. PMID:24267647

  5. 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 ...

  6. 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

  7. Unprotected left main percutaneous coronary intervention in acute coronary syndromes with extracorporeal life support backup.

    PubMed

    Staudacher, Dawid L; Langner, Oliver; Biever, Paul; Benk, Christoph; Zehender, Manfred; Bode, Christoph; Wengenmayer, Tobias

    2015-01-01

    Background. Left main PCI is superior to coronary bypass surgery in selected patients. Registry data, however, suggest significant early adverse event rates associated with unprotected left main PCI. We aimed to evaluate safety of an extracorporeal life support (ECLS) as backup system during PCI. Methods. We report a registry study of 16 high-risk patients presenting with acute coronary syndromes undergoing unprotected left main PCI with an ECLS backup. Results. Seven patients (43.8%) presented with an acute myocardial infarction while 9 patients (56.3%) had unstable angina. Unprotected left main PCI could be successfully performed in all 16 patients. Mortality or thromboembolic event rates were zero within the index hospital stay. General anesthesia was necessary only in 5 patients (31.3%). Access site bleeding requiring transfusion was encountered in 4 patients (25.0%). Three patients (18.8%) developed access site complications requiring surgical intervention. All patients were ECLS-free after 96 hours. Conclusions. Unprotected left main PCI could be safely and effectively performed after ECLS implantation as backup in acute coronary syndromes in our patient collectively. Vascular access site complications however need to be considered when applying ECLS as backup system.

  8. Vascular pattern formation in plants.

    PubMed

    Scarpella, Enrico; Helariutta, Ykä

    2010-01-01

    Reticulate tissue systems exist in most multicellular organisms, and the principles underlying the formation of cellular networks have fascinated philosophers, mathematicians, and biologists for centuries. In particular, the beautiful and varied arrangements of vascular tissues in plants have intrigued mankind since antiquity, yet the organizing signals have remained elusive. Plant vascular tissues form systems of interconnected cell files throughout the plant body. Vascular cells are aligned with one another along continuous lines, and vascular tissues differentiate at reproducible positions within organ environments. However, neither the precise path of vascular differentiation nor the exact geometry of vascular networks is fixed or immutable. Several recent advances converge to reconcile the seemingly conflicting predictability and plasticity of vascular tissue patterns. A control mechanism in which an apical-basal flow of signal establishes a basic coordinate system for body axis formation and vascular strand differentiation, and in which a superimposed level of radial organizing cues elaborates cell patterns, would generate a reproducible tissue configuration in the context of an underlying robust, self-organizing structure, and account for the simultaneous regularity and flexibility of vascular tissue patterns.

  9. Vascular trauma in civilian practice.

    PubMed Central

    Golledge, J.; Scriven, M. W.; Fligelstone, L. J.; Lane, I. F.

    1995-01-01

    Vascular trauma is associated with major morbidity and mortality, but little is known about its incidence or nature in Britain. A retrospective study of 36 patients requiring operative intervention for vascular trauma under one vascular surgeon over a 6-year period was undertaken. Twenty-four patients suffered iatrogenic trauma (median age 61 years); including cardiological intervention (19), radiological intervention (2), varicose vein surgery (1), umbilical vein catherisation (1) and isolated hyperthermic limb perfusion (1). There were 23 arterial and three venous injuries. Twelve patients had accidental trauma (median age 23 years). Three of the ten patients with blunt trauma were referred for vascular assessment before orthopaedic intervention, two after an on-table angiogram and five only after an initial orthopaedic procedure (range of delay 6 h to 10 days). Injuries were arterial in nine, venous in two and combined in one. Angiography was obtained in six patients, and in two patients with multiple upper limb fractures identified the site of injury when clinical localisation was difficult. A variety of vascular techniques were used to treat the injuries. Two patients died postoperatively and one underwent major limb amputation. Thirty-two (89%) remain free of vascular sequelae after a median follow-up of 48 months (range 3-72 months). Vascular trauma is uncommon in the United Kingdom. To repair the injuries a limited repertoire of vascular surgery techniques is needed. Therefore, vascular surgical assessment should be sought at an early stage to prevent major limb loss. PMID:8540659

  10. Acute Decompensated Heart Failure

    PubMed Central

    Joseph, Susan M.; Cedars, Ari M.; Ewald, Gregory A.; Geltman, Edward M.; Mann, Douglas L.

    2009-01-01

    Hospitalizations for acute decompensated heart failure are increasing in the United States. Moreover, the prevalence of heart failure is increasing consequent to an increased number of older individuals, as well as to improvement in therapies for coronary artery disease and sudden cardiac death that have enabled patients to live longer with cardiovascular disease. The main treatment goals in the hospitalized patient with heart failure are to restore euvolemia and to minimize adverse events. Common in-hospital treatments include intravenous diuretics, vasodilators, and inotropic agents. Novel pharmaceutical agents have shown promise in the treatment of acute decompensated heart failure and may simplify the treatment and reduce the morbidity associated with the disease. This review summarizes the contemporary management of patients with acute decompensated heart failure. PMID:20069075

  11. Vascularization of engineered teeth.

    PubMed

    Nait Lechguer, A; Kuchler-Bopp, S; Hu, B; Haïkel, Y; Lesot, H

    2008-12-01

    The implantation of cultured dental cell-cell re-associations allows for the reproduction of fully formed teeth, crown morphogenesis, epithelial histogenesis, mineralized dentin and enamel deposition, and root-periodontium development. Since vascularization is critical for organogenesis and tissue engineering, this work aimed to study: (a) blood vessel formation during tooth development, (b) the fate of blood vessels in cultured teeth and re-associations, and (c) vascularization after in vivo implantation. Ex vivo, blood vessels developed in the dental mesenchyme from the cap to bell stages and in the enamel organ, shortly before ameloblast differentiation. In cultured teeth and re-associations, blood-vessel-like structures remained in the peridental mesenchyme, but never developed into dental tissues. After implantation, both teeth and re-associations became revascularized, although later in the case of the re-associations. In implanted re-associations, newly formed blood vessels originated from the host, allowing for their survival, and affording conditions organ growth, mineralization, and enamel secretion.

  12. Vascular Distribution of Nanomaterials

    PubMed Central

    Stapleton, Phoebe A.; Nurkiewicz, Timothy R.

    2014-01-01

    Once considered primarily occupational, novel nanotechnology innovation and application has led to widespread domestic use and intentional biomedical exposures. With these exciting advances, the breadth and depth of toxicological considerations must also be expanded. The vascular system interacts with every tissue in the body, striving to homeostasis. Engineered nanomaterials (ENM) have been reported to distribute in many different organs and tissues. However, these observations have tended to use approaches requiring tissue homogenization and/or gross organ analyses. These techniques, while effective in establishing presence, preclude an exact determination of where ENM are deposited within a tissue. It is necessary to identify this exact distribution and deposition of ENM throughout the cardiovascular system, with respect to vascular hemodynamics and in vivo/ in vitro ENM modifications taken into account if nanotechnology is to achieve its full potential. Distinct levels of the vasculature will first be described as individual compartments. Then the vasculature will be considered as a whole. These unique compartments and biophysical conditions will be discussed in terms of their propensity to favor ENM deposition. Understanding levels of the vasculature will also be discussed. Ultimately, future studies must verify the mechanisms speculated on and presented herein. PMID:24777845

  13. Vascular graft infections.

    PubMed

    Hasse, Barbara; Husmann, Lars; Zinkernagel, Annelies; Weber, Rainer; Lachat, Mario; Mayer, Dieter

    2013-01-01

    Vascular procedures are rarely complicated by infection, but if prosthetic vascular graft infection (PVGI) occurs, morbidity and mortality are high. Several patient-related, surgery-related and postoperative risk factors are reported, but they are not well validated. PVGI is due to bacterial colonisation of the wound and the underlying prosthetic graft, generally as a result of direct contamination during the operative procedure, mainly from the patient's skin or adjacent bowel. There is no consensus on diagnostic criteria or on the best management of PVGI. On the basis of reported clinical studies and our own experience, we advocate a surgical approach combining repeated radical local debridement, with graft preservation whenever possible or partial excision of the infected graft, depending on its condition, plus simultaneous negative-pressure wound therapy (NPWT). In addition, antimicrobial therapy is recommended, but there is no consensus on which classes of agent are adequate for the treatment of PVGI and whether certain infections may be treated by means of NPWT alone. Since staphylococci and Gram-negative rods are likely to be isolated, empirical treatment might include a penicillinase-resistant beta-lactam or a glycopeptide, plus an aminoglycoside, the latter for Gram-negative coverage and synergistic treatment of Gram-positive cocci. Additionally, empirical treatment might include rifampicin since it penetrates well into biofilms.

  14. 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.

  15. 219 vascular fellows' perception of the future of vascular surgery.

    PubMed

    Hingorani, Anil P; Ascher, Enrico; Marks, Natalie; Shiferson, Alexander; Puggioni, Alessandra; Tran, Victor; Patel, Nirav; Jacob, Theresa

    2009-01-01

    In an attempt to identify the fellows' concerns about the future of the field of vascular surgery, we conducted a survey consisting of 22 questions at an annual national meeting in March from 2004 to 2007. In order to obtain accurate data, all surveys were kept anonymous. The fellows were asked (1) what type of practice they anticipated they would be in, (2) what the new training paradigm for fellows should be, (3) to assess their expectation of the needed manpower with respect to the demand for vascular surgeons, (4) what were major threats to the future of vascular surgery, (5) whether they had heard of and were in favor of the American Board of Vascular Surgery (ABVS), (6) who should be able to obtain vascular privileges, and (7) about their interest in an association for vascular surgical trainees. Of 273 attendees, 219 (80%) completed the survey. Males made up 87% of those surveyed, and 60% were between the ages of 31 and 35 years. Second-year fellows made up 82% of those surveyed. Those expecting to join a private, academic, or mixed practice made up 35%, 28%, and 20% of the respondents, respectively, with 71% anticipating entering a 100% vascular practice. Forty percent felt that 5 years of general surgery with 2 years of vascular surgery should be the training paradigm, while 45% suggested 3 and 3 years, respectively. A majority, 79%, felt that future demand would exceed the available manpower, while 17% suggested that manpower would meet demand. The major challenges to the future of vascular surgery were felt to be competition from cardiology (82%) or radiology (30%) and lack of an independent board (29%). Seventeen percent were not aware of the ABVS, and only 2% were against it; 71% suggested that vascular privileges be restricted to board-certified vascular surgeons. Seventy-six percent were interested in forming an association for vascular trainees to address the issues of the future job market (67%), endovascular training during fellowship (56

  16. 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. PMID:25656991

  17. 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

  18. [Aortofemoral vascular graft infections and their prevention].

    PubMed

    Taher, F; Assadian, O; Hirsch, K; Falkensammer, J; Senekowitsch, C; Assadian, A

    2015-03-01

    Vascular prosthesis infections are potentially severe adverse events following vascular reconstruction. They are often associated with a high morbidity and mortality, especially in the aortofemoral region. The present article outlines the diagnosis, prevention and treatment of vascular graft infections in a clinical setting. The clinical presentation, inflammatory markers, microbiological work-up and imaging studies can contribute to diagnosing a prosthesis infection. Regarding the bacterial spectrum involved in the etiology of prosthesis infections, single organism infections (monoinfections) have become less significant over the past years, whereas infections with multiple organisms now constitute the most abundant microbiological constellation. Also, infections with resistant bacterial strains have been increasing in number over the past years and deserve special consideration. It remains unclear whether both aspects are due to a true epidemiological change or are the result of advanced molecular microbiological diagnostic methods. While during the past decades perioperative antibiotic prophylaxis was regarded as the most important measure for preventing prosthesis infections in vascular surgery, other primary preventive hygiene strategies have been increasingly explored and grouped together in the sense of preventive bundles. In most cases of deep postoperative infections involving a prosthetic device in the aortofemoral region, explantation of the prosthesis will be required. In situ and extra-anatomical reconstructions are often performed in such cases and the decision process to develop an optimal treatment plan must consider several individual factors. In select patients, palliative preservation of the prosthesis despite surrounding infection (i.e. graft salvage) and best conservative management in combination with local surgical measures, such as incision and drainage and vacuum therapy, deserve consideration as a treatment option for patients with a high

  19. Leukemia regression by vascular disruption and antiangiogenic therapy

    PubMed Central

    Madlambayan, Gerard J.; Meacham, Amy M.; Hosaka, Koji; Mir, Saad; Jorgensen, Marda; Scott, Edward W.; Siemann, Dietmar W.

    2010-01-01

    Acute myelogenous leukemias (AMLs) and endothelial cells depend on each other for survival and proliferation. Monotherapy antivascular strategies such as targeting vascular endothelial growth factor (VEGF) has limited efficacy in treating AML. Thus, in search of a multitarget antivascular treatment strategy for AML, we tested a novel vascular disrupting agent, OXi4503, alone and in combination with the anti-VEGF antibody, bevacizumab. Using xenotransplant animal models, OXi4503 treatment of human AML chloromas led to vascular disruption in leukemia cores that displayed increased leukemia cell apoptosis. However, viable rims of leukemia cells remained and were richly vascular with increased VEGF-A expression. To target this peripheral reactive angiogenesis, bevacizumab was combined with OXi4503 and abrogated viable vascular rims, thereby leading to enhanced leukemia regression. In a systemic model of primary human AML, OXi4503 regressed leukemia engraftment alone and in combination with bevacizumab. Differences in blood vessel density alone could not account for the observed regression, suggesting that OXi4503 also exhibited direct cytotoxic effects on leukemia cells. In vitro analyses confirmed this targeted effect, which was mediated by the production of reactive oxygen species and resulted in apoptosis. Together, these data show that OXi4503 alone is capable of regressing AML by a multitargeted mechanism and that the addition of bevacizumab mitigates reactive angiogenesis. PMID:20472832

  20. HABP2 is a Novel Regulator of Vascular Integrity

    PubMed Central

    Mambetsariev, N.; Mirzapoiazova, T.; Mambetsariev, B.; Sammani, S.; Lennon, F.E.; Garcia, J.G.N.; Singleton, P.A.

    2010-01-01

    Objective We evaluated the role of the extracellular serine protease, Hyaluronic Acid Binding Protein 2 (HABP2), in vascular barrier regulation. Methods and Results Using immunoblot and immunohistochemical analysis, we observed that lipopolysaccharide (LPS)-induces HABP2 expression in murine lung endothelium in vivo and in human pulmonary microvascular endothelial cell (HPMVEC) in vitro. High molecular weight hyaluronan (HMW-HA, ~1 million Da) decreased HABP2 protein expression in HPMVEC and decreased purified HABP2 enzymatic activity whereas low MW HA (LMW-HA, ~2,500 Da) increased these activities. The effects of LMW-HA on HABP2 activity, but not HMW-HA, were inhibited with a peptide of the polyanion binding domain (PABD) of HABP2. Silencing (siRNA) HABP2 expression augmented HMW-HA-induced EC barrier enhancement and inhibited LPS and LMW-HA-mediated EC barrier disruption, results which were reversed with overexpression of HABP2. Silencing PAR receptors 1 and 3, RhoA or ROCK expression attenuated LPS, LMW-HA and HABP2-mediated EC barrier disruption. Utilizing murine models of acute lung injury, we observed that LPS- and ventilator-induced pulmonary vascular hyper-permeability were significantly reduced with vascular silencing (siRNA) of HABP2. Conclusions HABP2 negatively regulates vascular integrity via activation of PAR receptor/RhoA/ROCK signaling and represents a potentially useful therapeutic target for syndromes of increased vascular permeability. PMID:20042707

  1. Contrast induced nephropathy in vascular surgery.

    PubMed

    Wong, G T C; Lee, E Y P; Irwin, M G

    2016-09-01

    Contrast induced nephropathy (CIN) is traditionally associated with outpatient imaging studies. More recently, patients afflicted with vascular pathologies are increasingly undergoing endovascular treatments that require the use of iodinated contrast media (CM) agents, thus placing them as risk of developing CIN. As perioperative physicians, anaesthetists should be aware of the risk factors and measures that might minimize acute kidney injury caused by CM. This review evaluates recent data regarding preventive measures against CIN and where possible, places the evidence in the context of the patient receiving endovascular surgical treatment. Measures including the use of peri-procedural hydration, N-acetylcysteine, statins, remote ischaemic preconditioning, renal vasodilators and renal replacement therapy and the use of alternatives to iodinated contrast agents are discussed. It should be noted that most of the available data regarding CIN are from non-surgical patients. PMID:27566809

  2. Vascular disrupting agents in clinical development

    PubMed Central

    Hinnen, P; Eskens, F A L M

    2007-01-01

    Growth of human tumours depends on the supply of oxygen and nutrients via the surrounding vasculature. Therefore tumour vasculature is an attractive target for anticancer therapy. Apart from angiogenesis inhibitors that compromise the formation of new blood vessels, a second class of specific anticancer drugs has been developed. These so-called vascular disrupting agents (VDAs) target the established tumour vasculature and cause an acute and pronounced shutdown of blood vessels resulting in an almost complete stop of blood flow, ultimately leading to selective tumour necrosis. As a number of VDAs are now being tested in clinical studies, we will discuss their mechanism of action and the results obtained in preclinical studies. Also data from clinical studies will be reviewed and some considerations with regard to the future development are given. PMID:17375046

  3. Poly(ADP-ribose) polymerase inhibition reverses vascular dysfunction after {gamma}-irradiation

    SciTech Connect

    Beller, Carsten J. . E-mail: Carsten.Beller@urz.uni-heidelberg.de; Radovits, Tamas; Seres, Leila; Kosse, Jens; Krempien, Robert; Gross, Marie-Luise; Penzel, Roland; Berger, Irina; Huber, Peter E.; Hagl, Siegfried; Szabo, Csaba; Szabo, Gabor

    2006-08-01

    Purpose: The generation of reactive oxygen species during {gamma}-irradiation may induce DNA damage, leading to activation of the nuclear enzyme poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) culminating in endothelial dysfunction. In the present study, we assessed the effect of PARP inhibition on changes in vascular function after acute and short-term irradiation. Methods and Materials: In the acute experiments, aortic rings were exposed to 20 Gy of {gamma}-irradiation. The aortae were harvested after 1 or 7 days. Two additional groups received the ultrapotent PARP inhibitor, INO-1001, for 1 or 7 days after irradiation. The aortic rings were precontracted by phenylephrine and relaxation to acetylcholine and sodium nitroprusside were studied. Results: The vasoconstrictor response to phenylephrine was significantly lower both acutely and 1 and 7 days after irradiation. Vasorelaxation to acetylcholine and sodium nitroprusside was not impaired acutely after irradiation. One and seven days after irradiation, vasorelaxation to acetylcholine and sodium nitroprusside was significantly enhanced. Treatment with INO-1001 reversed vascular dysfunction after irradiation. Conclusion: Vascular dysfunction was observed 1 and 7 days after irradiation, as evidenced by reduced vasoconstriction, coupled with endothelium-dependent and -independent hyperrelaxation. PARP inhibition restored vascular function and may, therefore, be suitable to reverse vascular dysfunction after irradiation.

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

    SciTech Connect

    Wendler, Johann Jakob; Pech, Maciej; Blaschke, Simon; Porsch, Markus; Janitzky, Andreas; Ulrich, Matthias; Dudeck, Oliver; Ricke, Jens; Liehr, Uwe-Bernd

    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 parenchyma 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.

  5. Prediction of cardiac events after uncomplicated myocardial infarction: a prospective study comparing predischarge exercise thallium-201 scintigraphy and coronary angiography

    SciTech Connect

    Gibson, R.S.; Watson, D.D.; Craddock, G.B.; Crampton, R.S.; Kaiser, D.L.; Denny, M.J.; Beller, G.A.

    1983-08-01

    The ability of predischarge quantitative exercise thallium-201 (/sup 201/T1) scintigraphy to predict future cardiac events was evaluated prospectively in 140 consecutive patients with uncomplicated acute myocardial infarction; the results were compared with those of submaximal exercise treadmill testing and coronary angiography. High risk was assigned if scintigraphy detected /sup 201/T1 defects in more than one discrete vascular region, redistribution, or increased lung uptake, if exercise testing caused ST segment depression greater than or equal to 1 mm or angina or if angiography revealed multivessel disease. Low risk was designated if scintigraphy detected a single-region defect, no redistribution, or no increase in lung uptake, if exercise testing caused no ST segment depression or angina, or if angiography revealed single-vessel disease or no disease. By 15 +/- 12 months, 50 patients had experienced a cardiac event; seven died (five suddenly), nine suffered recurrent myocardial infarction, and 34 developed severe class III or IV angina pectoris. Compared with that of patients at low risk, the cumulative probability of a cardiac event was greater in high-risk patients identified by scintigraphy, exercise testing, or angiography. Scintigraphy predicted low-risk status better than exercise testing or angiography. Each predicted mortality with equal accuracy. These results indicate that (1) submaximal exercise /sup 201/T1 scintigraphy can distinguish high- and low-risk groups after uncomplicated acute myocardial infarction before hospital discharge; (2) /sup 201/T1 defects in more than one discrete vascular region, presence of delayed redistribution, or increased lung thallium uptake are more sensitive predictors of subsequent cardiac events than ST segment depression, angina, or extent of angiographic disease; and (3) low-risk patients are best identified by a single-region /sup 201/T1 defect without redistribution and no increased lung uptake.

  6. Adiponectin as a potential biomarker of vascular disease

    PubMed Central

    Ebrahimi-Mamaeghani, Mehrangiz; Mohammadi, Somayeh; Arefhosseini, Seyed Rafie; Fallah, Parviz; Bazi, Zahra

    2015-01-01

    The increasing prevalence of diabetes and its complications heralds an alarming situation worldwide. Obesity-associated changes in circulating adiponectin concentrations have the capacity to predict insulin sensitivity and are a link between obesity and a number of vascular diseases. One obvious consequence of obesity is a decrease in circulating levels of adiponectin, which are associated with cardiovascular disorders and associated vascular comorbidities. Human and animal studies have demonstrated decreased adiponectin to be an independent risk factor for cardiovascular disease. However, in animal studies, increased circulating adiponectin alleviates obesity-induced endothelial dysfunction and hypertension, and also prevents atherosclerosis, myocardial infarction, and diabetic cardiac tissue disorders. Further, metabolism of a number of foods and medications are affected by induction of adiponectin. Adiponectin has beneficial effects on cardiovascular cells via its antidiabetic, anti-inflammatory, antioxidant, antiapoptotic, antiatherogenic, vasodilatory, and antithrombotic activity, and consequently has a favorable effect on cardiac and vascular health. Understanding the molecular mechanisms underlying the regulation of adiponectin secretion and signaling is critical for designing new therapeutic strategies. This review summarizes the recent evidence for the physiological role and clinical significance of adiponectin in vascular health, identification of the receptor and post-receptor signaling events related to the protective effects of the adiponectin system on vascular compartments, and its potential use as a target for therapeutic intervention in vascular disease. PMID:25653535

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

    SciTech Connect

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

    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)

  8. 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

  9. The association between vibration and vascular injury in rheumatic diseases: a review of the literature.

    PubMed

    Wang, Yu-Jie; Huang, Xiao-Lei; Yan, Jun-Wei; Wan, Ya-Nan; Wang, Bing-Xiang; Tao, Jin-Hui; Chen, Bing; Li, Bao-Zhu; Yang, Guo-Jun; Wang, Jing

    2015-02-01

    Vascular manifestations can be seen early in the pathogenesis of inflammatory rheumatic diseases. Animal experiments, laboratory and clinical findings indicated that acute or long-term vibration exposure can induce vascular abnormalities. Recent years, in addition to Raynaud's phenomenon (RP), vibration as a risk factor for other rheumatic diseases has also received corresponding considered. This review is concentrated upon the role of vibration in the disease of systemic sclerosis (SSc). In this review, we are going to discuss the main mechanisms which are thought to be important in pathophysiology of vascular injury under the three broad headings of "vascular", "neural" and "intravascular". Aspects on the vibration and vascular inflammation are briefly discussed. And the epidemiological studies related to vibration studies in SSc and other rheumatic diseases are taken into account.

  10. Vascular mineralization in the brain of horses.

    PubMed

    Martínez, Jorge; Montgomery, Donald L; Uzal, Francisco A

    2012-05-01

    Vascular mineralization (siderocalcinosis) in the brain of horses has been usually assumed to be an incidental age-related finding with no clinic significance. In the present study, eight 15-32-year-old horses of different breeds with cerebral siderocalcinosis were studied. Four of these horses had acute and severe central nervous system clinical signs of unknown etiology, 2 horses had neurological signs of known cause, and 2 horses did not have neurological signs. Gross examination of the brains in 4 animals revealed symmetrical foci of malacia in the cerebellar white matter. Histologically, moderate to severe mineralization of blood vessels and parenchyma were observed in all 8 horses, occasionally associated with necrosis of the adjacent tissue. Some horses were tested by virus isolation, polymerase chain reaction, immunohistochemistry, and serology to investigate Rabies virus; West Nile virus; Equid herpesvirus 1 and 4; Eastern, Western, Venezuelan, and Saint Louis encephalitis virus; and Sarcocystis neurona infection. These tests were negative in all samples analyzed. Brain cholinesterase activity and heavy metal screening were also unremarkable. The significance of the vascular and parenchymal mineralization in the brains of some of these horses remains undetermined. However, the severity of the lesions observed in the brains of some of the animals in the present study, coupled with the negative results for other common causes of neurological disease in horses, suggests a possible relationship between siderocalcinosis and the clinical signs observed.

  11. Vascular surgery: the European perspective.

    PubMed

    Harris, P

    1999-09-01

    Isaac Newton, among others, observed that 'we see so far because we are standing upon the shoulders of giants'. In vascular surgery most of the giants have been European, and this is a heritage which we as Europeans can take pride in and build upon if we chose to do so. As in other areas of life, commitment is essential in order to influence the future. For vascular surgeons in Europe this means active participation in the European scientific societies for vascular surgery and in the UEMS. The main value of the EBSQ.VASC assessments to date has been to expose the uneven standards of training in vascular surgery within the European Union. Only if action follows to address these inequalities will the tactics of the European Board of Vascular Surgery be vindicated.

  12. Caffeine's Vascular Mechanisms of Action

    PubMed Central

    Echeverri, Darío; Montes, Félix R.; Cabrera, Mariana; Galán, Angélica; Prieto, Angélica

    2010-01-01

    Caffeine is the most widely consumed stimulating substance in the world. It is found in coffee, tea, soft drinks, chocolate, and many medications. Caffeine is a xanthine with various effects and mechanisms of action in vascular tissue. In endothelial cells, it increases intracellular calcium stimulating the production of nitric oxide through the expression of the endothelial nitric oxide synthase enzyme. Nitric oxide is diffused to the vascular smooth muscle cell to produce vasodilation. In vascular smooth muscle cells its effect is predominantly a competitive inhibition of phosphodiesterase, producing an accumulation of cAMP and vasodilation. In addition, it blocks the adenosine receptors present in the vascular tissue to produce vasoconstriction. In this paper the main mechanisms of action of caffeine on the vascular tissue are described, in which it is shown that caffeine has some cardiovascular properties and effects which could be considered beneficial. PMID:21188209

  13. [Cerebrolysin for acute ischemic stroke].

    PubMed

    iganshina, L E; Abakumova, T R

    2013-01-01

    The review discusses existing evidence of benefits and risks of cerebrolysin--a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue with proposed neuroprotective and neurotrophic properties, for acute ischemic stroke. The review presents results of systematic search and analysis of randomised clinical trials comparing cerebrolysin with placebo in patients with acute ischemic stroke. Only one trial was selected as meeting quality criteria. No difference in death and adverse events between cerebrolysin and placebo was established. The authors conclude about insufficiency of evidence to evaluate the effect of cerebrolysin on survival and dependency in people with acute ischemic stroke.

  14. Visualization of Vascular and Parenchymal Regeneration after 70% Partial Hepatectomy in Normal Mice.

    PubMed

    Xie, Chichi; Wei, Weiwei; Schenk, Andrea; Schwen, Lars Ole; Zafarnia, Sara; Schwier, Michael; Gremse, Felix; Jank, Isabel; Dirsch, Olaf; Dahmen, Uta

    2016-01-01

    A modified silicone injection procedure was used for visualization of the hepatic vascular tree. This procedure consisted of in-vivo injection of the silicone compound, via a 26 G catheter, into the portal or hepatic vein. After silicone injection, organs were explanted and prepared for ex-vivo micro-CT (µCT) scanning. The silicone injection procedure is technically challenging. Achieving a successful outcome requires extensive microsurgical experience from the surgeon. One of the challenges of this procedure involves determining the adequate perfusion rate for the silicone compound. The perfusion rate for the silicone compound needs to be defined based on the hemodynamic of the vascular system of interest. Inappropriate perfusion rate can lead to an incomplete perfusion, artificial dilation and rupturing of vascular trees. The 3D reconstruction of the vascular system was based on CT scans and was achieved using preclinical software such as HepaVision. The quality of the reconstructed vascular tree was directly related to the quality of silicone perfusion. Subsequently computed vascular parameters indicative of vascular growth, such as total vascular volume, were calculated based on the vascular reconstructions. Contrasting the vascular tree with silicone allowed for subsequent histological work-up of the specimen after µCT scanning. The specimen can be subjected to serial sectioning, histological analysis and whole slide scanning, and thereafter to 3D reconstruction of the vascular trees based on histological images. This is the prerequisite for the detection of molecular events and their distribution with respect to the vascular tree. This modified silicone injection procedure can also be used to visualize and reconstruct the vascular systems of other organs. This technique has the potential to be extensively applied to studies concerning vascular anatomy and growth in various animal and disease models. PMID:27685096

  15. Emerging treatment options to improve cardiovascular outcomes in patients with acute coronary syndrome: focus on losmapimod

    PubMed Central

    Kragholm, Kristian; Newby, Laura Kristin; Melloni, Chiara

    2015-01-01

    Each year, despite optimal use of recommended acute and secondary prevention therapies, 4%–5% of patients with acute coronary syndrome (ACS) experience relapse of ACS or other cardiovascular events<