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The outcome of patients presenting to the emergency department with severe sepsis or septic shock
Emanuel Rivers
Critical Care , 2006, DOI: 10.1186/cc4973
Abstract: A recent retrospective, observational study by Ho and coworkers [1] measured the incidence and outcome of septic patients presenting at an Australian emergency department (ED) with criteria for early goal-directed therapy (EGDT) and found significantly fewer EGDT candidates than previous studies [2]. A number of initiatives aiming to reduce worldwide mortality associated with sepsis, such as the Surviving Sepsis Campaign, have previously noted the importance of the tenets of early hemodynamic optimization to try and overcome this devastating disease. In patients with severe sepsis or septic shock, clinicians must be aware that a considerable proportion of those with significant lactic acidosis can have near normal serum bicarbonate or normal calculated anion gap values, which may lead to underestimated disease severity [3-5]. In the EGDT study [2], of the patients enrolled with a lactate level greater than 4 mmol/l, more than 30% had a bicarbonate level greater than 22 and an anion gap of less than or equal to 15 mEq/l. Other studies have shown that even if an anion gap is present, the mortality rate is significantly higher for lactic acidosis (56%) than for strong ion gap acidosis (39%) and hyperchloremic acidosis (29%) [6]. Despite mentioning lactate as a criterion in the study, Ho and coworkers did not report data regarding the levels or number of measurements found. Thus, it is possible that they underestimated the prevalence of high-risk patients in need of early hemodynamic optimization. This may explain why they strikingly found only 50 patients over 3.5 years (14.2 per year) meeting criteria for severe sepsis and septic shock in a large teaching hospital emergency department (ED) that sees 40,000 patients each year with a 30% admission rate.The lactate level of 4 mmol/l, as used in the EGDT study, was internally and externally validated. In their study of 1218 patients, Aduen and colleagues [3] found that lactate concentrations above 4 mmol/l were 98.2% spec
Clinical manifestations of disordered microcirculatory perfusion in severe sepsis
Stephen Trzeciak, Emanuel P Rivers
Critical Care , 2005, DOI: 10.1186/cc3744
Abstract: Microcirculatory blood flow is markedly impaired in sepsis [1-3], and microcirculatory dysfunction plays a pivotal role in the development of the clinical manifestations of severe sepsis and septic shock. In the past, direct visualization of microcirculatory networks was only possible in experimental models of sepsis using intravital videomicroscopy, which is not possible in human subjects. Newly developed imaging technologies, such as orthogonal polarization spectral (OPS) imaging, have brought the ability to directly visualize the microcirculation to the bedside. Microcirculatory imaging, however, is still investigational in human sepsis and has not yet been incorporated into routine clinical practice. The purpose of this review, therefore, is to bridge the experimental and clinical aspects of microcirculatory science, and discuss the concepts that can be incorporated into bedside assessments of patients with severe sepsis and septic shock.Although the hemodynamic profile and clinical management of septic shock are typically characterized solely in terms of global hemodynamic (i.e. macrovascular) parameters, it is the microcirculation that is responsible for delivering blood flow from the cardiovascular system to the tissues. After conventional cardiovascular support measures achieve restoration of an acceptable arterial blood pressure in a septic shock patient, a clinician may be falsely reassured that the patient is clinically 'stable'. However, there are a myriad of possible pathogenic mechanisms occurring in the microcirculation that are difficult to detect with conventional clinical means and are, in effect, hidden from the clinician. In fact, much of the pathophysiology of severe sepsis can be explained by 'what lies beneath' in the microcirculation [4]. In severe sepsis this can include: (1) global tissue hypoxia [5]; (2) pan-endothelial cell injury [6]; (3) activation of the coagulation cascade [7]; and (4) "microcirculatory and mitochondrial distress synd
Impact of Cardiac Contractility during Cerebral Blood Flow in Ischemia
Wira, Charles,Rivers, Emanuel,Silver, Brian,Lewandowski, Christopher
Western Journal of Emergency Medicine : Integrating Emergency Care with Population Health , 2011,
Abstract: Objective: In cerebral regions affected by ischemia, intrinsic vascular autoregulation is often lost. Blood flow delivery depends upon cardiac function and may be influenced by neuro-endocrine mediated myocardial suppression. Our objective is to evaluate the relation between ejection fraction (EF) and transcranial doppler (TCD) peak systolic velocities (PSV) in patients with cerebral ischemic events.Methods: We conducted a retrospective cohort study from an existing TCD registry. We evaluated patients admitted within 24 hours of onset of a focal neurological deficit who had an echocardiogram and TCD performed within 72 hours of admission.Results: We identified 58 patients from March to October 2003. Eighty-one percent (n=47) had a hospital discharge diagnosis of ischemic stroke and 18.9% (n=11) had a diagnosis of transient ischemic attack. Fourteen patients had systolic dysfunction (EF50%) compared to those with systolic dysfunction (EF<50%) was as follows: middle cerebral artery 62.0 + 28.6 cm/s vs. 51.0 + 23.3 cm/s, p=0.11; anterior cerebral artery 52.1 + 21.6 cm/s vs. 45.9 + 22.7 cm/s, p=0.28; internal carotid artery 56.5 + 20.1 cm/s vs. 46.4 + 18.4 cm/s, p=0.04; ophthalmic artery 18.6 + 7.2 cm/s vs. 15.3 + 5.2 cm/s, p=0.11; vertebral artery 34.0 + 13.9 cm/s vs. 31.6 + 15.0 cm/s, p=0.44.Conclusion: Cerebral blood flow in the internal carotid artery territory appears to be higher in cerebral ischemia patients with preserved left ventricular contractility. Our study was unable to differentiate pre-existing cardiac dysfunction from neuro-endocrine mediated myocardial stunning. Future research is necessary to better understand heart-brain interactions in this setting and to further explore the underlying mechanisms and consequences of neuro-endocrine mediated cardiac dysfunction. [West J Emerg Med. 2011;12(2):227-232.]
Reducing mortality in sepsis: new directions
Jean-Louis Vincent, Edward Abraham, Djillali Annane, Gordon Bernard, Emanuel Rivers, Greet Van den Berghe
Critical Care , 2002, DOI: 10.1186/cc1860
Abstract: Sepsis is the tenth most common cause of death in the US [1]. A recent US study reported that severe sepsis accounts for in excess of 215,000 deaths annually from a total population of approximately 750,000 patients – a mortality rate of approximately 29% (with published studies quoting a range of 28–50%) [2].This persistent, high mortality rate is clearly unacceptable, given that it ranks sepsis above some of the higher profile causes of in-hospital death, including stroke (12–19% risk of death in the first 30 days) and acute myocardial infarction (AMI) (8% risk of death in the first 30 days) [3]. Moreover, the actual number of deaths associated with the condition may be even higher than current estimates suggest. Many sepsis patients have at least one comorbidity and deaths are often attributed to these conditions rather than to sepsis [4,5,6]. Unfamiliarity with the signs and symptoms of sepsis may further hinder accurate diagnosis.There are many possible reasons for this high mortality. Sepsis is certainly a complex disease state; the pathophysiology is only now beginning to be unraveled, and it is complicated by heterogeneous presentation (possible signs of sepsis are presented in Table 1). While none of these signs alone is specific for sepsis, the otherwise unexplained presence of these signs should signal the possibility of a septic response.Many cases of sepsis are recognized late, and patients are often inappropriately treated before entering the intensive care unit (ICU) by physicians unfamiliar with the signs and symptoms of the condition. Furthermore, treatment may be initiated by any of a number of physicians (anesthetists, hematologists, intensivists, infectious disease specialists, pulmonologists, and emergency physicians). There are presently various defined supportive strategies for treating patients with sepsis, but improvements are needed to reduce the unacceptably high mortality rate.Moreover, as with other areas of medicine, the application and
Cardiac Complications in Acute Ischemic Stroke
Charles R Wira,Emanuel Rivers,Cynthia Martinez-Capolino,Brian Silver
Western Journal of Emergency Medicine : Integrating Emergency Care with Population Health , 2011,
Abstract: Introduction: To characterize cardiac complications in acute ischemic stroke (AIS) patients admitted from an urban emergency department (ED). Methods: Retrospective cross-sectional study evaluating AIS patients admitted from the ED within 24 hours of symptom onset who also had an echocardiogram performed within 72 hours of admission. Results: Two hundred AIS patients were identified with an overall in-hospital mortality rate of 8% (n 16). In our cohort, 57 (28.5%) of 200 had an ejection fraction less than 50%, 35 (20.4%) of 171 had ischemic changes on electrocardiogram (ECG), 18 (10.5%) of 171 presented in active atrial fibrillation, 21 (13.0%) of 161 had serum troponin elevation, and 2 (1.1%) of 184 survivors had potentially lethal arrhythmias on telemetry monitoring. Subgroup analysis revealed higher in-hospital mortality rates among those with systolic dysfunction (15.8% versus 4.9%; P 0.0180), troponin elevation (38.1% versus 3.4%; P , 0.0001), atrial fibrillation on ECG (33.3% versus 3.8%; P 0.0003), and ischemic changes on ECG (17.1% versus 6.1%; P 0.0398) compared with those without. Conclusion: A proportion of AIS patients may have cardiac complications. Systolic dysfunction, troponin elevation, atrial fibrillation, or ischemic changes on ECG may be associated with higher inhospital mortality rates. These findings support the adjunctive role of cardiac-monitoring strategies in the acute presentation of AIS. [West J Emerg Med. 2011;12(4):414–420.]
Technology as a Mode and Manifestation of Being: An Assessment of Its Applications  [PDF]
Theodore John Rivers
Advances in Historical Studies (AHS) , 2013, DOI: 10.4236/ahs.2013.23018
Abstract: The objective of this paper is to demonstrate how technology’s being is revealed through its applications, which is expressive by means of the mode and manifestation of its being. The designation of technology as a mode of being refers to its nature, and the designation of technology as a manifestation of being refers to its activity as proof of technology’s being. Both mode and manifestation indicate how the being of technology is applied. Although distinguishable as two aspects of technology, both mode and manifestation are essential to revealing the essence of technology and its interplay with the world. Since human culture has a technological underpinning, the applications of technology not only reveal its metaphysics, but also indicate its importance to human culture. In addition to technology’s underlying method, these applications also pertain to the artifacts (or objects) of invention, mathematics, the consciousness of time, writing, alphabetization, science, and society.
Technology and Being: A Discussion of Their Metaphysical Significance  [PDF]
Theodore John Rivers
Advances in Historical Studies (AHS) , 2015, DOI: 10.4236/ahs.2015.41005
Abstract: This paper discusses the relationship between various metaphysical ideas associated with technology and the concept of being, notably in reference to the becoming of being, which is a description for change. And change influences technology in many ways when expressed through the mode and manifestation of its being. As a mode of being, technology is the means or manner by which we do anything. Consequently, mode is an effect of action as well as a cause for other actions yet to occur. As a manifestation of being, technology becomes the predominant way in which humanity presents itself to the world. Since we have aligned our being with technology, and have even on many occasions sublimated ourselves to it, it may be argued that our relationship with technology is simply a revelation of our desire to be.
Cognitive Robotics: For Never Was a Story of More Woe than This  [PDF]
Emanuel Diamant
Journal of Computer and Communications (JCC) , 2014, DOI: 10.4236/jcc.2014.211005

We are now on the verge of the next technical revolution—robots are going to invade our lives. However, to interact with humans or to be incorporated into a human “collective” robots have to be provided with some human-like cognitive abilities. What does it mean?—Nobody knows. But, robotics research communities are trying hard to find out a way to cope with this problem. Meanwhile, despite abundant funding these efforts did not lead to any meaningful result (only in Europe, only in the past ten years, Cognitive Robotics research funding has reached a ceiling of 1.39 billion euros). In the next ten years, a similar budget is going to be spent to tackle the Cognitive Robotics problems in the frame of the Human Brain Project. There is no reason to expect that this time the result will be different. We would like to try to explain why we are so unhappy about this.

Early lactate clearance is associated with biomarkers of inflammation, coagulation, apoptosis, organ dysfunction and mortality in severe sepsis and septic shock
H Bryant Nguyen, Manisha Loomba, James J Yang, Gordon Jacobsen, Kant Shah, Ronny M Otero, Arturo Suarez, Hemal Parekh, Anja Jaehne, Emanuel P Rivers
Journal of Inflammation , 2010, DOI: 10.1186/1476-9255-7-6
Abstract: Measurements of serum arterial lactate, biomarkers (interleukin-1 receptor antagonist, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha, intercellular adhesion molecule-1, high mobility group box-1, D-Dimer and caspase-3), and organ dysfunction scores (Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology Score II, Multiple Organ Dysfunction Score, and Sequential Organ Failure Assessment) were obtained in conjunction with a prospective, randomized study examining early goal-directed therapy in severe sepsis and septic shock patients presenting to the emergency department (ED). Lactate clearance was defined as the percent change in lactate levels after six hours from a baseline measurement in the ED.Two-hundred and twenty patients, age 65.0 +/- 17.1 years, were examined, with an overall lactate clearance of 35.5 +/- 43.1% and in-hospital mortality rate of 35.0%. Patients were divided into four quartiles of lactate clearance, -24.3 +/- 42.3, 30.1 +/- 7.5, 53.4 +/- 6.6, and 75.1 +/- 7.1%, respectively (p < 0.01). The mean levels of all biomarkers and organ dysfunction scores over 72 hours were significantly lower with higher lactate clearance quartiles (p < 0.01). There was a significant decreased in-hospital, 28-day, and 60-day mortality in the higher lactate clearance quartiles (p < 0.01).Early lactate clearance as a surrogate for the resolution of global tissue hypoxia is significantly associated with decreased levels of biomarkers, improvement in organ dysfunction and outcome in severe sepsis and septic shock.The transition from sepsis to severe sepsis and septic shock is associated with a number of hemodynamic perturbations leading to global tissue hypoxia. Global tissue hypoxia accompanies a myriad of pathogenic mechanisms which contribute to the development of the multi-system organ dysfunction syndrome and increased mortality [1,2]. Although there is significant interaction between inflammation, coagulation and
Zinc Complexes of New Chiral Aminophenolate Ligands: Synthesis, Characterization and Reactivity toward Lactide  [PDF]
Pascal Binda, Kimberly Rivers, Clifford Padgett
Open Journal of Inorganic Chemistry (OJIC) , 2016, DOI: 10.4236/ojic.2016.63016
Abstract: The syntheses of a library of new chiral aminophenolate bidentate O,N-type ligands HOC6H4(2-R- 4-R′)CH2N(Me)CH(Me)C6H5 [R = R′ = But, 1; R = R′ = Pent, 2; R = But, R′ = Me, 3; R = Me, R′ = But, 4; R = R′ = Me, 5] and tridentate O,N,O-type ligands HOC6H4(2,4-But)CH = NCH(R′′)C6H5 [R′′ = Me, 6; R′′ = CH2OMe, 7] are reported. These ligands were characterized by elemental analysis, nuclear magnetic resonance spectroscopy (1H & 13C), and single crystal X-ray diffraction. These ligands serve as chiral auxiliaries for inorganic chemists to design chiral metal-based complexes for asymmetric catalysis and stereoselective polymerization reactions. Three new heteroleptic zinc complexes based on these ligands have been synthesized in moderate yields via a ligand-exchange transamination reaction between homoleptic [Zn(N(SiMe3)2)2] and one equivalent of corresponding ligands to afford [L3ZnN- (SiMe3)2] (3a), [L4ZnN(SiMe3)2] (4a), and [L7ZnN(SiMe3)2] (7a). Solvent-free polymerization of raclactide at 130°C using these zinc compounds yielded atactic polylactides with Mw 10,000 g/mol and narrow polydispersity of 1.3.
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