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Search Results: 1 - 10 of 34093 matches for " John Marshall "
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Vascular Endothelial Growth Factor Plus Epidermal Growth Factor Receptor Dual Targeted Therapy in Metastatic Colorectal Cancer: Synergy or Antagonism?
John L. Marshall
Journal of Oncology , 2009, DOI: 10.1155/2009/937305
Abstract: There has been an intensive effort to develop novel therapies forthe treatment of metastatic colorectal cancer (mCRC). Theanti-epidermal growth factor receptor (EGFR) antibodiespanitumumab and cetuximab and the anti-vascular endothelial growthfactor (VEGF) antibody bevacizumab have demonstrated clinicalefficacy and acceptable toxicity in the treatment of mCRC assingle agents or in combination with chemotherapy. Recent clinicaltrials have explored the efficacy and safety of treatment regimensincorporating chemotherapy in combination with bevacizumab andeither panitumumab or cetuximab in patients with mCRC. Resultsfrom the BOND-2 trial, which investigated cetuximab, bevacizumab,and chemotherapy in mCRC, provided support for this therapeuticapproach. Two large randomized phase 3 trials were initiated toevaluate firstline treatment of mCRC. The Panitumumab AdvancedColorectal Cancer Evaluation (PACCE) study investigated theefficacy and safety of oxaliplatin- or irinotecan-basedchemotherapy and bevacizumab with or without panitumumab; CAIRO2assessed the efficacy and safety of capecitabine/oxaliplatin andbevacizumab with or without cetuximab. In both trials, thecombination of bevacizumab, an EGFR-specific antibody, andchemotherapy in first-line treatment of mCRC was associated withincreased toxicity and no improvement in patient outcome. Theseresults suggest that these specific combinations should not beused in first-line mCRC outside investigational studies.
New Translational Research Provides Insights into Liver Dysfunction in Sepsis
John C. Marshall
PLOS Medicine , 2012, DOI: 10.1371/journal.pmed.1001341
Transfusion trigger: when to transfuse?
John C Marshall
Critical Care , 2004, DOI: 10.1186/cc2846
Abstract: The normal hemoglobin level in the healthy individual is greater than 130 g/l. In the ambulatory patient levels below this are considered to represent anemia and trigger a search for potentially correctable causes, including sources of occult blood loss. However, the hemoglobin level of most hospitalized patients and, in particular, patients in an intensive care unit (ICU) falls substantially below this normal range. Multiple factors are responsible, including acute blood loss, dilution secondary to fluid retention and depressed hematopoiesis. At a certain level of anemia, the surgeon becomes concerned that reduced oxygen-carrying capacity may be detrimental to the patient's welfare and considers transfusion. The level that should trigger this decision has until recently been largely unknown.The rationale for blood transfusion is rooted in the physiology of oxygen delivery. Oxygen delivery to the tissues (DO2) depends upon the concentration of hemoglobin (Hb), the percent saturation of that hemoglobin (SaO2), and the cardiac output (CO):DO2 = Hb × %SaO2 × COA reduction in oxygen delivery below a critical level deprives tissues of the oxygen necessary for oxidative metabolism and results in a shift to anaerobic metabolism. Because oxygen requirement by tissues may be increased during acute stresses, it is intuitive that maintaining adequate oxygen delivery will result in improved clinical outcome. Indeed, the concept that supranormal oxygen delivery was desirable led intensivists to devise strategies to increase oxygen delivery in critical illness to supraphysiologic levels [1]. The benefits of such an approach, however, have not been borne out by randomized controlled trials [2].In theory, manipulation of hemoglobin, oxygen saturation, and/or cardiac output should increase oxygen delivery. However, hemoglobin is normally almost fully saturated with oxygen, and increasing cardiac output in the face of adequate filling pressures requires the use of inotropic agents. T
Measurements in the intensive care unit: what do they mean?
John C Marshall
Critical Care , 2003, DOI: 10.1186/cc2400
Abstract: Measurement is the currency of critical care. Illness in the intensive care unit is defined not by pathologic changes in a particular tissue or by structural changes in a specific organ, but by a constellation of quantifiable changes in physiological and biochemical measures. To round in an intensive care unit is to be exposed to a cacophony of numbers – the pH, the Glasgow Coma Scale, the fibrinogen level. To be an intensivist means to take this chaotic melange of digits and to transform them into a clinical profile that will support a therapeutic decision. An uninitiated visitor to a contemporary intensive care unit could be forgiven for concluding that the intensivity of intensive care referred to the zeal with which its practitioners measure things: the continuous recording of the pulse, the blood pressure and the transcutaneous oxygen saturation, and the frequent assay of circulating factors whose function is familiar (e.g. potassium or hemoglobin) as well as those factors whose biologic significance is less so. High on the list of those less significant factors is procalcitonin.In the present issue of Critical Care, Level and colleagues report the results of a carefully conducted cohort study of 15 patients undergoing continuous venovenous hemodialysis [1]. They show that procalcitonin (PCT) is cleared by continuous venovenous hemodialysis at conventional filtration rates and that the protein adsorbs to the filter, so as much as 20% of PCT is removed through the membrane. The consequences of this removal are modest, however, and are probably not clinically significant. Also, the residual plasma levels remain essentially constant.What message should the beleaguered intensivist, struggling to maintain a focus in the face of an onslaught of new measures and new sources of uncertainty, take from this report? I believe there are two: one message regarding the utility of PCT as a diagnostic marker, and the second message addressing the more fundamental question of h
Iatrogenesis, inflammation and organ injury: insights from a murine model
John C Marshall
Critical Care , 2006, DOI: 10.1186/cc5087
Abstract: The multiple organ dysfunction syndrome – the common final pathway to death for the majority of critically ill patients who succumb in the intensive care unit – is an enormously complex and elusive process. Support of acute organ system insufficiency is the raison d'être of intensive care and is the embodiment of the remarkable successes of a relatively young discipline. However, organ system support itself can exacerbate the very injury it seeks to support, and despite apparently successful resuscitation and intensive care unit management of the critically ill, de novo organ dysfunction, remote to the site of the original insult, commonly evolves in the most seriously ill patients. The intricate interactions of an acute life-threatening insult with the profound homeostatic derangements that follow resuscitation, and the superimposed injury caused by the need for organ system support, are poorly understood; they are largely ignored in our attempts to replicate critical illness using animal models.In the preceding issue of Critical Care, O'Mahony and colleagues [1], from the University of Washington, describe an elegant series of studies that probe the capacity of two relatively trivial insults to synergize to produce remote organ injury. The first of these insults is microbial (intraperitoneal challenge with lipopolysaccharide) and the second is iatrogenic (mechanical ventilation at a conventional tidal volume). Their observations echo those of others [2,3], namely that the synergistic interaction of two subclinical insults can result in clinically important organ injury that is much more severe than might be predicted on the basis of either of the two component insults. This observation – colloquially termed the 'two-hit hypothesis' of multiple organ failure – represents an important refinement in our understanding of the way in which activation of innate immunity can produce the phenotypic alterations of critical illness. In study conducted by O'Mahony and colleag
The staging of sepsis: understanding heterogeneity in treatment efficacy
John C Marshall
Critical Care , 2005, DOI: 10.1186/cc3907
Abstract: To the casual observer, the patients who inhabit a contemporary intensive care unit must present a single and frightening image. All are dressed in the same custom issue intensive care unit garb, and all are confined to bed – the passive recipients of a bewildering array of life support technologies. Each has a variable number of plastic tubes emanating from a number of orifices, both anatomic and iatrogenic, and through these tubes is receiving unknown fluids, or expelling those that are only too familiar. Most are on mechanical ventilators, and beds that are capable of quite remarkable contortions. Some are undergoing dialysis, while others seem to be making an agonizing effort to return to a state of coherence and autonomy. But it is their similarities, rather than their differences, that create the most enduring impression.To the intensivist caring for these patients, however, the picture is much more complex. The course of this otherwise well young woman struggling to survive the consequences of a pregnancy complicated by a placental abruption and disseminated intravascular coagulation may be rendered more complicated by a ventilator-associated pneumonia. But for the elderly man in the next bed, who lacking family or friends to make a decision in the final days of his life was admitted with a further exacerbation of chronic lung disease, the same pneumonia holds the elusive possibility of a dignified death. Across the way is a middle-aged man with an anastomotic leak following an esophagectomy who has now developed acute renal failure, and an elderly woman admitted last night with shock, and a poorly characterized infiltrate on the chest X-ray. For each of these individuals, sustaining life is a relatively simple matter of identifying the physiological insult or insults that comprises an immediate threat, and initiating the appropriate means of exogenous support, be it mechanical ventilation, dialysis, or vasoactive medications. The much greater, and largely un
The International Sepsis Forum's controversies in sepsis: how will sepsis be treated in 2051?
John C Marshall
Critical Care , 2002, DOI: 10.1186/cc1539
Abstract: It is a sobering experience to be faced with a blank page and to be asked to speculate on what we might be doing 49 years from now. I will not be treating sepsis in 2051 because I won't be here. The chances are, however, that future intensivists will not really be treating 'sepsis' either. Let me explain.By the middle of the 21st century we will finally have a definition of sepsis. For instance, this is what you might read in the 2048 edition of a medical dictionary:sepsis (sep·sis). A generic term that describes a group of diseases that result from the systemic expression of acute inflammation.By then, the epidemiology of sepsis will have changed; sepsis will be more common because it is an iatrogenic disorder – a consequence of the successes that we have had in critical care medicine. However, mortality will have decreased profoundly, partly because of new therapies and partly because we will understand the pathophysiology better. Depending on the stage of sepsis, mortality will be no more than 5%, in large part because we will finally accept that it is legitimate to die from natural causes, and those deaths will no longer be attributed to sepsis.Today our tools for the diagnosis of infection are limited to microbial cultures, radiologic investigations, and direct examination. Selecting appropriate antibiotic therapy is difficult because culture and sensitivity data are not immediately available. It is not difficult to imagine, however, that in the future we will have rapid point of care diagnostic technology based on detecting microbial products and even antibiotic resistance genes.At present we see the microbial world as largely inimical, and we take extraordinary measures to eradicate it. In the future we will have a better understanding of 'host–microbial symbiosis'. We will understand that the successful treatment of infection is grounded not just in eliminating a pathogen but also in supporting the indigenous flora of the host. We will administer micro-organ
Therapeutic Hypothermia for Acute Air Embolic Stroke
Matthew Chang,John Marshall
Western Journal of Emergency Medicine : Integrating Emergency Care with Population Health , 2012,
Abstract: [West J Emerg Med. 2012;13(1):111–113.]
How Xenopus laevis replicates DNA reliably even though its origins of replication are located and initiated stochastically
John Bechhoefer,Brandon Marshall
Quantitative Biology , 2006, DOI: 10.1103/PhysRevLett.98.098105
Abstract: DNA replication in Xenopus laevis is extremely reliable, failing to complete before cell division no more than once in 10,000 times; yet replication origins sites are located and initiated stochastically. Using a model based on 1d theories of nucleation and growth and using concepts from extreme-value statistics, we derive the distribution of replication times given a particular initiation function. We show that the experimentally observed initiation strategy for Xenopus laevis meets the reliability constraint and is close to the one that requires the fewest resources of a cell.
Does the Nature of Chief Complaint, Gender, or Age Affect Time to Be Seen in the Emergency Room  [PDF]
Ayesha Sattar, Kenneth Sable, Antonios Likourezos, Christian Fromm, John Marshall
Open Journal of Emergency Medicine (OJEM) , 2014, DOI: 10.4236/ojem.2014.22006

Objectives: EM physicians may be biased in seeing patients presenting with nonspecific complaints or requiring more extensive work-ups. The goal of our study was to ascertain if chief complaint affected time to be seen (TTBS) in the ED. Methods: A retrospective report was generated from the EMR for all moderate acuity patients who visited the ED from January 2005 to December 2010 at a large urban teaching hospital. Abdominal pain, alcohol intoxication, back pain, chest pain, cough, dyspnea, dizziness, fall, fever, flank pain, headache, infection, pain (nonspecific), psychiatric evaluation, “sent by MD”, vaginal bleeding, vomiting, and weakness were the most common complaints. Non-Parametric Independent Sample Tests assessed median TTBS between complaints, gender, and age. Chisquare testing assessed for differences in the distribution of arrival times. Results: We obtained data from 116,194 patients. Patients presenting with weakness and dizziness waited the longest time of 35 minutes and patients with flank pain waited the shortest with 24 minutes. Males waited 30 minutes and females waited 32 minutes. Younger females between the ages of 18 - 50 waited significantly longer when presenting with a chief complaint of abdominal pain, chest pain, or flank pain. There was no difference in the distribution of arrival times for these complaints. Conclusion: There is a significant bias toward seeing young male patients more quickly than women or older males. Patients might benefit from efforts to educate EM physicians on the delays and potential quality issues associated with this bias in an attempt to move toward more egalitarian patient selection.

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