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Severe hypoxemia presents variably, and sometimes silently, without subjective complaints of dyspnea. The adequacy of cardiovascular compensation for oxygen delivery to tissues should be a focus in all hypoxemic patients.
Philip E. Bickler; John R. Feiner; Michael S. Lipnick; William McKleroy. “Silent” Presentation of Hypoxemia and Cardiorespiratory Compensation in COVID-19. Anesthesiology 2020, 134, 262 -269.
AMA StylePhilip E. Bickler, John R. Feiner, Michael S. Lipnick, William McKleroy. “Silent” Presentation of Hypoxemia and Cardiorespiratory Compensation in COVID-19. Anesthesiology. 2020; 134 (2):262-269.
Chicago/Turabian StylePhilip E. Bickler; John R. Feiner; Michael S. Lipnick; William McKleroy. 2020. "“Silent” Presentation of Hypoxemia and Cardiorespiratory Compensation in COVID-19." Anesthesiology 134, no. 2: 262-269.
Philip E. Bickler; John R. Feiner; Michael S. Lipnick; William McKleroy. “Silent” Presentation of Hypoxemia and Cardiorespiratory Compensation in COVID-19. 2020, 1 .
AMA StylePhilip E. Bickler, John R. Feiner, Michael S. Lipnick, William McKleroy. “Silent” Presentation of Hypoxemia and Cardiorespiratory Compensation in COVID-19. . 2020; ():1.
Chicago/Turabian StylePhilip E. Bickler; John R. Feiner; Michael S. Lipnick; William McKleroy. 2020. "“Silent” Presentation of Hypoxemia and Cardiorespiratory Compensation in COVID-19." , no. : 1.
Background: Older aged adults and those with pre-existing conditions are at highest risk for severe COVID-19 associated outcomes. Methods: Using a large dataset of genome-wide RNA-seq profiles derived from human dermal fibroblasts (GSE113957) we investigated whether age affects the expression of pattern recognition receptor (PRR) genes and ACE2, the receptor for SARS-CoV-2. Results: Older age was associated with increased expression of PRR genes, ACE2 and four genes that encode proteins that have been shown to interact with SAR2-CoV-2 proteins. Conclusions: Assessment of PRR expression might provide a strategy for stratifying the risk of severe COVID-19 disease at both the individual and population levels.
Stephen W. Bickler; David M. Cauvi; Kathleen M. Fisch; James M. Prieto; Alicia D. Gaidry; Hariharan Thangarajah; David Lazar; Romeo Ignacio; Dale R. Gerstmann; Allen F. Ryan; Philip E. Bickler; Antonio De Maio. Age is Associated With Increased Expression of Pattern Recognition Receptor Genes and ACE2, the Receptor for SARs-Cov-2: Implications for the Epidemiology of COVID-19 Disease. 2020, 1 .
AMA StyleStephen W. Bickler, David M. Cauvi, Kathleen M. Fisch, James M. Prieto, Alicia D. Gaidry, Hariharan Thangarajah, David Lazar, Romeo Ignacio, Dale R. Gerstmann, Allen F. Ryan, Philip E. Bickler, Antonio De Maio. Age is Associated With Increased Expression of Pattern Recognition Receptor Genes and ACE2, the Receptor for SARs-Cov-2: Implications for the Epidemiology of COVID-19 Disease. . 2020; ():1.
Chicago/Turabian StyleStephen W. Bickler; David M. Cauvi; Kathleen M. Fisch; James M. Prieto; Alicia D. Gaidry; Hariharan Thangarajah; David Lazar; Romeo Ignacio; Dale R. Gerstmann; Allen F. Ryan; Philip E. Bickler; Antonio De Maio. 2020. "Age is Associated With Increased Expression of Pattern Recognition Receptor Genes and ACE2, the Receptor for SARs-Cov-2: Implications for the Epidemiology of COVID-19 Disease." , no. : 1.
Older aged adults and those with pre-existing conditions are at highest risk for severe COVID-19 associated outcomes. Using a large dataset of genome-wide RNA-seq profiles derived from human dermal fibroblasts (GSE113957) we investigated whether age affects the expression of pattern recognition receptor (PRR) genes and ACE2, the receptor for SARS-CoV-2. Older age was associated with increased expression of PRR genes, ACE2 and four genes that encode proteins that have been shown to interact with SAR2-CoV-2 proteins. Assessment of PRR expression might provide a strategy for stratifying the risk of severe COVID-19 disease at both the individual and population levels.
Stephen W. Bickler; David M. Cauvi; Kathleen M. Fisch; James M. Prieto; Alicia D. Gaidry; Hariharan Thangarajah; David Lazar; Romeo Ignacio; Dale R. Gerstmann; Allen F. Ryan; Philip E. Bickler; Antonio De Maio. AGE IS ASSOCIATED WITH INCREASED EXPRESSION OF PATTERN RECOGNITION RECEPTOR GENES AND ACE2, THE RECEPTOR FOR SARS-COV-2: IMPLICATIONS FOR THE EPIDEMIOLOGY OF COVID-19 DISEASE. 2020, 1 .
AMA StyleStephen W. Bickler, David M. Cauvi, Kathleen M. Fisch, James M. Prieto, Alicia D. Gaidry, Hariharan Thangarajah, David Lazar, Romeo Ignacio, Dale R. Gerstmann, Allen F. Ryan, Philip E. Bickler, Antonio De Maio. AGE IS ASSOCIATED WITH INCREASED EXPRESSION OF PATTERN RECOGNITION RECEPTOR GENES AND ACE2, THE RECEPTOR FOR SARS-COV-2: IMPLICATIONS FOR THE EPIDEMIOLOGY OF COVID-19 DISEASE. . 2020; ():1.
Chicago/Turabian StyleStephen W. Bickler; David M. Cauvi; Kathleen M. Fisch; James M. Prieto; Alicia D. Gaidry; Hariharan Thangarajah; David Lazar; Romeo Ignacio; Dale R. Gerstmann; Allen F. Ryan; Philip E. Bickler; Antonio De Maio. 2020. "AGE IS ASSOCIATED WITH INCREASED EXPRESSION OF PATTERN RECOGNITION RECEPTOR GENES AND ACE2, THE RECEPTOR FOR SARS-COV-2: IMPLICATIONS FOR THE EPIDEMIOLOGY OF COVID-19 DISEASE." , no. : 1.
The active components of snake venoms encompass a complex and variable mixture of proteins that produce a diverse, but largely stereotypical, range of pharmacologic effects and toxicities. Venom protein diversity and host susceptibilities determine the relative contributions of five main pathologies: neuromuscular dysfunction, inflammation, coagulopathy, cell/organ injury, and disruption of homeostatic mechanisms of normal physiology. In this review, we describe how snakebite is not only a condition mediated directly by venom, but by the amplification of signals dysregulating inflammation, coagulation, neurotransmission, and cell survival. Although venom proteins are diverse, the majority of important pathologic events following envenoming follow from a small group of enzyme-like activities and the actions of small toxic peptides. This review focuses on two of the most important enzymatic activities: snake venom phospholipases (svPLA2) and snake venom metalloproteases (svMP). These two enzyme classes are adept at enabling venom to recruit homologous endogenous signaling systems with sufficient magnitude and duration to produce and amplify cell injury beyond what would be expected from the direct impact of a whole venom dose. This magnification produces many of the most acutely important consequences of envenoming as well as chronic sequelae. Snake venom PLA2s and MPs enzymes recruit prey analogs of similar activity. The transduction mechanisms that recruit endogenous responses include arachidonic acid, intracellular calcium, cytokines, bioactive peptides, and possibly dimerization of venom and prey protein homologs. Despite years of investigation, the precise mechanism of svPLA2-induced neuromuscular paralysis remains incomplete. Based on recent studies, paralysis results from a self-amplifying cycle of endogenous PLA2 activation, arachidonic acid, increases in intracellular Ca2+ and nicotinic receptor deactivation. When prolonged, synaptic suppression supports the degeneration of the synapse. Interaction between endothelium-damaging MPs, sPLA2s and hyaluronidases enhance venom spread, accentuating venom-induced neurotoxicity, inflammation, coagulopathy and tissue injury. Improving snakebite treatment requires new tools to understand direct and indirect effects of envenoming. Homologous PLA2 and MP activities in both venoms and prey/snakebite victim provide molecular targets for non-antibody, small molecule agents for dissecting mechanisms of venom toxicity. Importantly, these tools enable the separation of venom-specific and prey-specific pathological responses to venom.
Philip E. Bickler. Amplification of Snake Venom Toxicity by Endogenous Signaling Pathways. Toxins 2020, 12, 68 .
AMA StylePhilip E. Bickler. Amplification of Snake Venom Toxicity by Endogenous Signaling Pathways. Toxins. 2020; 12 (2):68.
Chicago/Turabian StylePhilip E. Bickler. 2020. "Amplification of Snake Venom Toxicity by Endogenous Signaling Pathways." Toxins 12, no. 2: 68.
There is an unmet need for economical snakebite therapies with long shelf lives that are effective even with delays in treatment. The orally bioavailable, heat-stable, secretory phospholipase A2 (sPLA2) inhibitor, LY333013, demonstrates antidotal characteristics for severe snakebite envenoming in both field and hospital use. A murine model of lethal envenoming by a Papuan taipan (Oxyuranus scutellatus) demonstrates that LY333013, even with delayed oral administration, improves the chances of survival. Furthermore, LY333013 improves the performance of antivenom even after it no longer reverses neurotoxic signs. Our study is the first demonstration that neurotoxicity from presynaptic venom sPLA2S can be treated successfully, even after the window of therapeutic antivenom has closed. These results suggest that sPLA2 inhibitors have the potential to reduce death and disability and should be considered for the initial and adjunct treatment of snakebite envenoming. The scope and capacity of the sPLA2 inhibitors ability to achieve these endpoints requires further investigation and development efforts.
Matthew R. Lewin; José María Gutiérrez; Stephen P. Samuel; María Herrera; Wendy Bryan-Quirós; Bruno Lomonte; Philip E. Bickler; Tommaso C. Bulfone; David J. Williams. Delayed Oral LY333013 Rescues Mice from Highly Neurotoxic, Lethal Doses of Papuan Taipan (Oxyuranus scutellatus) Venom. Toxins 2018, 10, 380 .
AMA StyleMatthew R. Lewin, José María Gutiérrez, Stephen P. Samuel, María Herrera, Wendy Bryan-Quirós, Bruno Lomonte, Philip E. Bickler, Tommaso C. Bulfone, David J. Williams. Delayed Oral LY333013 Rescues Mice from Highly Neurotoxic, Lethal Doses of Papuan Taipan (Oxyuranus scutellatus) Venom. Toxins. 2018; 10 (10):380.
Chicago/Turabian StyleMatthew R. Lewin; José María Gutiérrez; Stephen P. Samuel; María Herrera; Wendy Bryan-Quirós; Bruno Lomonte; Philip E. Bickler; Tommaso C. Bulfone; David J. Williams. 2018. "Delayed Oral LY333013 Rescues Mice from Highly Neurotoxic, Lethal Doses of Papuan Taipan (Oxyuranus scutellatus) Venom." Toxins 10, no. 10: 380.
Philip Bickler; John R. Feiner; Jenny Lundeberg. Response to Burtscher re: “Increased Cytokines at High Altitude: Lack of Effect of Ibuprofen on Acute Mountain Sickness, Physiological Variables, or Cytokine Levels”. High Altitude Medicine & Biology 2018, 19, 304 -305.
AMA StylePhilip Bickler, John R. Feiner, Jenny Lundeberg. Response to Burtscher re: “Increased Cytokines at High Altitude: Lack of Effect of Ibuprofen on Acute Mountain Sickness, Physiological Variables, or Cytokine Levels”. High Altitude Medicine & Biology. 2018; 19 (3):304-305.
Chicago/Turabian StylePhilip Bickler; John R. Feiner; Jenny Lundeberg. 2018. "Response to Burtscher re: “Increased Cytokines at High Altitude: Lack of Effect of Ibuprofen on Acute Mountain Sickness, Physiological Variables, or Cytokine Levels”." High Altitude Medicine & Biology 19, no. 3: 304-305.
BACKGROUND: The relationship between inhalational anesthetics such as isoflurane and cognitive impairment in the elderly is controversial. Both β-amyloid peptide (Aβ), associated with Alzheimer disease, and tumor necrosis factor-α (TNF-α), a proinflammatory stress-related peptide, impair the synaptic function. We hypothesized that transient exposure to isoflurane and these peptides would impair synaptic function, manifest as a depression of long-term potentiation (LTP) and paired pulse facilitation (PPF), in the rat hippocampus. METHODS: Hippocampal slices were prepared from 3- to 4-week-old male Wistar rats. Preliminary experiments identified minimal concentrations of Aβ1–42 peptide and TNF-α that produced statistically detectable suppressing effects on LTP (600 nM Aβ1–42 and 5 ng/mL TNF-α). These concentrations of peptides were applied to slices alone, with 1.5% isoflurane, or in combination for 1 hour and then washed out. Measurements of LTP (field excitatory postsynaptic potentials [fEPSPs]) from neurons in the CA1 area by stimulation of the Schaffer-Collateral pathway were made after high-frequency stimulation (100 Hz, 1 second). Analysis of variance with correction for multiple comparisons was used to compare LTP under steady-state conditions and averaged for the 40- to 60-minute period after LTP induction. RESULTS: EPSP amplitude after LTP induction was 155% ± 9% of baseline and was not affected by isoflurane exposure and washout (150% ± 4% of baseline, P = .47). Both Aβ1–42 and TNF-α reduced LTP by approximately 15% compared with control (129% ± 7% and 131% ± 11% of baseline respectively, means ± SD, both P < .001). When Aβ1–42 was combined with isoflurane, LTP was not impaired (151% ± 9% of control, P = .85), but isoflurane had no effect on LTP depression caused by TNF-α or a combination of Aβ and TNF-α. CONCLUSIONS: Brief exposure to isoflurane prevents rather than impairs the decrease in LTP caused by Aβ1–42 in rat hippocampus. In contrast, isoflurane had no effect on synaptic impairment caused by TNF-α or a combination of TNF-α and Aβ. Although this is an in vitro study and translation to clinical medicine requires additional work, the interactions of isoflurane, Aβ, and TNF-α revealed here could have implications for patients with Alzheimer disease or perioperative neuroinflammation.
Ran Zhou; Philip Bickler. Interaction of Isoflurane, Tumor Necrosis Factor-α and β-Amyloid on Long-term Potentiation in Rat Hippocampal Slices. Anesthesia & Analgesia 2017, 124, 582 -587.
AMA StyleRan Zhou, Philip Bickler. Interaction of Isoflurane, Tumor Necrosis Factor-α and β-Amyloid on Long-term Potentiation in Rat Hippocampal Slices. Anesthesia & Analgesia. 2017; 124 (2):582-587.
Chicago/Turabian StyleRan Zhou; Philip Bickler. 2017. "Interaction of Isoflurane, Tumor Necrosis Factor-α and β-Amyloid on Long-term Potentiation in Rat Hippocampal Slices." Anesthesia & Analgesia 124, no. 2: 582-587.
Philip E. Bickler. Enough Information to Evaluate Clinical Monitors? Anesthesia & Analgesia 2016, 123, 254 -255.
AMA StylePhilip E. Bickler. Enough Information to Evaluate Clinical Monitors? Anesthesia & Analgesia. 2016; 123 (1):254-255.
Chicago/Turabian StylePhilip E. Bickler. 2016. "Enough Information to Evaluate Clinical Monitors?" Anesthesia & Analgesia 123, no. 1: 254-255.