1,720,972 research outputs found
Intravenous pyruvate to protect heart and brain during closed-chest resuscitation and recovery from cardiac arrest
No full textCardiac arrest is a leading cause of death in the United States and Western Europe. Cardiopulmonary resuscitation (CPR) is the only means of sustaining the victim until application of defibrillatory countershocks. Although it has been over 50 years since its advent, CPR remains a work in progress. Many initially resuscitated victims later die from the damage sustained from ischemia-reperfusion, and treatments to combat the extensive ischemia-reperfusion injury sustained during cardiac arrest-resuscitation remain elusive. The major mechanism of injury underlying ischemia-reperfusion is the intense overproduction of reactive oxygen and nitrogen species (RONS) that accumulate during reperfusion and compromise normal cell function. RONS formed during resuscitation trigger lipid peroxidation, disable enzymes vital for cell metabolism and survival and, ultimately, induce cell death within affected organs. In order to prevent extensive damage to the central nervous system culminating in permanent neurocognitive disability and death, prospective treatments must possess robust antioxidant properties, traverse the blood-brain barrier between the cerebral circulation and brain parenchyma, and be non-toxic at effective doses.
Pyruvate is a natural intermediary metabolite, energy-yielding substrate and antioxidant. Pyruvate neutralizes RONS, thereby dampening oxidative stress and preventing covalent oxidative modification of enzymes and lipid membranes, and generates ATP to support brain function. Pyruvate readily traverses the blood-brain barrier and is non-toxic over a wide range of doses, including those previously demonstrated to protect the heart during cardiopulmonary bypass and the brain during stroke, thereby supporting oxygen and fuel delivery to the recovering brain. Moreover, pyruvate has been shown to promote cardiac electromechanical and metabolic recovery following cardiac arrest and open-chest CPR.
This study tested whether infusion of pyruvate during, CPR and early recovery can decrease the biomarkers of oxidative stress after cardiac arrest. Isoflurane-anesthetized pigs were subjected to 6 min electrically-induced, untreated ventricular fibrillation, followed by 4 min closed-chest CPR, defibrillation and either 1 or 4 h recovery. Beginning at 5.5 min arrest, either sodium pyruvate or NaCl control were infused iv for the duration of CPR and for the first 60 min after recovery of spontaneous circulation (ROSC). Arterial blood was sampled pre-arrest and at 5, 15, 30, 60, 120, 180, and 240 min ROSC for analyses of blood gases and plasma constituents. At either 1 h (i.e. end of treatment infusion) or 4 h ROSC, a craniotomy was performed, the pig was euthanized, the brain was removed, and biopsies from hippocampus and cerebellum were snap-frozen in liquid nitrogen for biochemical analysis.
The first phase of this project tested the hypothesis that intravenous administration of sodium pyruvate during precordial compressions and the first 60 min ROSC restores hemodynamic, metabolic, and electrolyte homeostasis in a closed chest porcine model of cardiac arrest. Resuscitation with pyruvate sharply decreased the incidence of lethal pulseless electrical activity (PEA) following defibrillatory countershocks, and lowered the dosage of vasoconstrictor phenylephrine required to maintain systemic arterial pressure. Pyruvate also enhanced glucose clearance, elevated arterial bicarbonate, and raised arterial pH.
The second phase of this project tested the hypothesis that pyruvate prevents the decrease in activity of the brain’s antioxidant enzymes following cardiac arrest and hyperoxic (100% O2). Activities of glutathione peroxidase and glutathione reductase were decreased at 60 min ROSC vs. sham in both the hippocampus and cerebellum. Pyruvate partially preserved glutathione peroxidase activity at 1 h ROSC, but by 4 h, after 3 h of pyruvate clearance from the circulation, the enzyme’s activity fell to the same extent as in NaCl-infused pigs. Interestingly, the glutathione peroxidase/reductase activity fell sharply in non-arrested sham pigs between the time points corresponding to 1 and 4 h ROSC, suggesting that hyperoxia resulting from ventilation with 100% produced sufficient oxidative stress to inactivate the enzymes. Similarly, lactate dehydrogenase activity fell between 1 and 4 h ROSC in hippocampus and especially cerebellum. In sham pigs, lactate dehydrogenase activity decreased from the time points corresponding to 1 and 4 h ROSC, and pyruvate had no effect on lactate dehydrogenase in either region of the brain. Thus, cardiac arrest and hyperoxic ventilation disabled a critical antioxidant system in two ischemia-sensitive brain regions. Pyruvate afforded partial protection of these enzymes which waned after pyruvate cleared from the circulation.
We conclude that 1) Pyruvate infusion during cardiac arrest, CPR and early recovery promotes conversion from ventricular fibrillation to a productive sinus rhythm instead of lethal PEA; 2) Pyruvate hastened glucose clearance, a prognostic measure used clinically; 3) Pyruvate elevated the arterial bicarbonate concentration and raised arterial pH, which combats the acidemia normally observed following ROSC; 4) Cardiac arrest-resuscitation and hyperoxic ventilation disabled the glutathione peroxidase-reductase system, a critical component of the brain’s antioxidant defenses, in hippocampus and cerebellum; and 5) Pyruvate delayed oxidative inactivation of glutathione peroxidase in the cerebellum, but this effect subsided as pyruvate elevated. These investigations demonstrate the therapeutic effects and limitations of pyruvate as a resuscitative treatment to hasten electrocardiographic and metabolic recovery post cardiac arrest
The Cephalic Vein: Anatomical Study and Evaluation of the Coracoid Process as a Topographical Bony Landmark
Full text linkINTRODUCTION. Clinicians require accurate anatomical information when gaining central venous access. Despite the cephalic vein cut down (CVCD) procedure being described as a superior choice to other methods, the cephalic vein's (CV) anatomical variations can make it challenging to locate. We asked if the coracoid process (CP) could be utilized as an accurate topographical landmark to locate the CV. The present study set out to prove the CV will be located within 1 cm of the CP with statistical significance. METHODS. We conducted bilateral shoulder dissections on 41 cadavers to determine the location of the CV in relation to the CP. Distances were measured horizontally, vertically and directly from the CP to the CV utilizing digital calipers. We also measured diameter via extracted veins where the inner luminal circumference was measured and divided by π to obtain diameter. SUMMARY. Resulting means were: Straight line distance: 9.48 ± 4.45 mm, horizontal distance: 13.50 ± 6.45 mm, vertical distance: 11.03 ± 5.17 mm, and diameter: 1.59 ± 0.67 mm. A one sample student t-test on the straight-line distance, with the expected population mean set to 10 mm so that the H0 indicates the data would be ≥ 10 mm and the Ha indicates the data was [less than] 10 mm. The α was set to 0.05, had a resulting p=0.333906 and the test statistics was -1.860547. From the results, the H0 was rejected. Since clinicians will likely have more than just 10 mm of open incision space while gaining access to the CV, the t-test was repeated with an expected population mean of 15 mm. The resulting p-value was 3.66613e-16 and the H0 was rejected. When α was set to 0.0001. The results remained significant. CONCLUSION. We showed that the CV can be located within 1 cm of the CP with statistical significance. The average incision for the CVCD procedure is 3-6 cm. It can safely be assumed that the incision will be spread to a width of 1.5 cm. If the clinician does not quickly locate the CV, they can assume it is likely deeper than the muscle belly, a variation or absent. This will aid clinicians in avoiding unnecessary time searching for the vein and instead rapidly transition to an alternative approach, transitioning the original CVCD incision to the reservoir incision. With this new information, we hope to persuade more clinicians to make the CVCD their first and primary attempt for central venous access over the subclavian puncture
ASSESSING THE PREVALENCE OF PSYCHOSOCIAL DISTRESS AMONG PEDIATRIC AND ADOLESCENT PATIENTS WITH LEUKEMIA USING THE DISTRESS THERMOMETER TOOL, AN OBSERVATIONAL STUDY
No full textA leukemia diagnosis causes psychosocial distress in a significant number of patients. When this psychosocial need goes unattended, it can negatively affect their course of treatment. To prevent this issue, the Distress Thermometer (DT) allows a quick and valid way for patients/parents to self-report distress on a scale of 0-10, including identification of the distress source. This study descriptively evaluates the differences in distress prevalence from different demographic factors such as ethnicity, gender, leukemia type, and age
Pyruvate-enriched Preservation of Machine Perfused Kidneys
Full text linkPurpose: Kidney transplantation remains the gold-standard treatment for patients diagnosed with end-stage renal disease (ESRD). However, the demand for donors currently far outpaces the supply. Kidneys donated after cardiac death (DCD) are a promising source, as cardiac arrest remains the leading cause of death in the United States. Studies have demonstrated the efficacy of hypothermic machine perfusion (HMP), a process by which kidneys are cannulated and perfused with a pulsatile flowing solution under hypothermic conditions, in reducing insult to organs compared to standard static cold storage (SCS) [1-3]. To date, perfusate additives to further optimize the outcomes of HMP preserved kidneys have not been extensively studied. The glycolytic end product, pyruvate, has demonstrated efficacy with protecting the heart from ischemia-reperfusion injury, improving post-ischemic contractile function of the heart through its function as an antioxidant and energy substrate, maintaining the glutathione redox state, and inducing erythropoietin production [4, 5]. We aim to investigate the impact of pyruvate on DCD kidneys maintained under HMP conditions. Methods: Cardiovascular death and a period of warm ischemia will be induced in a large animal model, the domestic pig. After explant, one kidney will serve as a pre-perfusion control and the other will be immediately flushed and cannulated to the HMP apparatus. The solutions perfusing the kidney in the HMP machine will consist of either a control perfusate or a pyruvate-enriched perfusate. Sample of the perfusate will be drawn periodically and cytokine concentration will be quantified. Tissue samples from the pre-perfused and 72-hour post-perfusion kidneys will be taken evaluated for both changes in renal tissue integrity via histological assessment and mRNA concentrations of various cytokines. Results: In pyruvate treated DCD kidneys, both renal cortex and renal medulla samples demonstrated better preserved tissue integrity compared to control. Additionally, markers for pro-inflammatory response markedly increased in the control group compared to the treatment group and vice versa for anti-inflammatory markers, including erythropoietin. Conclusions: We expect pyruvate preserved DCD kidneys will experience improved preservation by dampening the rate of increase of pro-inflammatory markers and increasing the concentration of anti-inflammatory markers
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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