103 results on '"Rogers JS"'
Search Results
2. Multicenter trial of EC145 in advanced, folate-receptor positive adenocarcinoma of the lung.
- Author
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Edelman MJ, Harb WA, Pal SE, Boccia RV, Kraut MJ, Bonomi P, Conley BA, Rogers JS, Messmann RA, and Garon EB
- Published
- 2012
- Full Text
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3. Can positron emission tomography be used as a staging tool for small-cell lung cancer?
- Author
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Vinjamuri M, Craig M, Campbell-Fontaine A, Almubarak M, Gupta N, and Rogers JS
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- 2008
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4. Immune reconstitution inflammatory syndrome and human immunodeficiency virus-associated myocarditis.
- Author
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Rogers JS, Zakaria S, Thom KA, Flammer KM, Kanno M, and Mehra MR
- Abstract
Myocarditis is a well-recognized cardiac manifestation of human immunodeficiency virus (HIV) infection, and alterations in the immune system likely play an important role in the pathogenesis of heart muscle disease in HIV-infected patients. Highly active antiretroviral therapy (HAART) has greatly improved survival in HIV patients but not without uncovering new and unique manifestations of disease. Immune reconstitution inflammatory syndrome is a collection of inflammatory disorders in which a pathologic inflammatory response and clinical deterioration occur during recovery of the immune system after HAART. To our knowledge, a correlation between immune reconstitution inflammatory syndrome and HIV-associated myocarditis has not been described previously. We report a case of acute myocarditis presenting with refractory ventricular arrhythmias in a patient with AIDS who experienced rapid immune recovery with the initiation of HAART. The case underscores the importance of recognizing this potential complication of AIDS treatment and calls for renewed vigilance concerning cardiac manifestations of HIV, especially during the immune reconstitution phase. [ABSTRACT FROM AUTHOR]
- Published
- 2008
5. Cloning and Characterization of Genes Conferring Copper Resistance in Epiphytic Ice Nucleation-ActivePseudomonas syringaeStrains
- Author
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Cirvilleri G, Rogers Js, Clark E, and Steven E. Lindow
- Subjects
Cloning ,Transposable element ,genomic DNA ,Cloning vector ,Cosmid ,Pseudomonas syringae ,Mutagenesis (molecular biology technique) ,Plant Science ,Biology ,Molecular cloning ,Agronomy and Crop Science ,Microbiology - Abstract
Many epiphytic Pseudomonas syringae strains obtained from asymptomatic host and nonhost plants are resistant to high concentrations of copper ions. A genomic DNA library of one such strain, AL513, was constructed in the broad host-range cosmid cloning vector pLAFR3. A cosmid designated pCOPR1.1 that conferred near wild-type levels of copper resistance when conjugated into the copper-sensitive (Cu s ) P. syringae strain AL487 was identified. A 6.5-kb PstI fragment in pCOPR1.1 conferred this copper resistance. Insertional inactivation mutagenesis of this cosmid with the reporter transposon Tn3-Spice indicated that a region of approximately 5.5 kb, denoted copJ, is required for copper resistance
- Published
- 1994
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6. Simultaneous palpation of the craniosacral rate at the head and feet: intrarater and interrater reliability and rate comparisons.
- Author
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Rogers JS, Witt PL, Gross MT, Hacke JD, and Genova PA
- Abstract
BACKGROUND AND PURPOSE: The main purpose of this study was to determine the interrater and intrarater reliability of measurements obtained during palpation of the craniosacral rate at the head and feet. Palpated craniosacral rates of head and feet measured simultaneously were also compared. Subjects. Twenty-eight adult subjects and 2 craniosacral examiners participated in the study. METHODS: A within-subjects repeated-measures design was used. A standard cubicle privacy curtain, hung over the subject's waist, was used to prevent the examiners from seeing each other. RESULTS: Interrater intraclass correlation coefficients (ICCs) were .08 at the head and .19 at the feet. Intrarater ICCs ranged from .18 to .30. Craniosacral rates simultaneously palpated at the head and feet were different. CONCLUSION AND DISCUSSION: The results did not support the theories that underlie craniosacral therapy or claims that craniosacral motion can be palpated reliably. [ABSTRACT FROM AUTHOR]
- Published
- 1998
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7. Intracranial Granulocytic Sarcoma in Postpolycythemia Myeloid Metaplasia
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Roy Ep rd, Rogers Js nd, and Jack E. Riggs
- Subjects
Male ,Time Factors ,Myeloid ,medicine.medical_treatment ,Polycythemia vera ,hemic and lymphatic diseases ,Metaplasia ,medicine ,Humans ,Polycythemia Vera ,Cerebral Cortex ,Brain Neoplasms ,business.industry ,Sarcoma ,General Medicine ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Magnetic Resonance Imaging ,Extramedullary hematopoiesis ,Radiation therapy ,medicine.anatomical_structure ,Leukemia, Myeloid ,Cancer research ,medicine.symptom ,Tomography, X-Ray Computed ,business ,Chronic myelogenous leukemia - Abstract
A 57-year-old man with a ten-year history of polycythemia vera had myeloid metaplasia, extramedullary hematopoiesis, and terminally, possible leukemic transformation with intracranial granulocytic sarcoma. Radiation therapy produced a partial and temporary beneficial response. Intracranial granulocytic sarcoma is typically associated with acute or chronic myelogenous leukemia and has not been previously associated with postpolycythemia myeloid metaplasia.
- Published
- 1989
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8. IgE myeloma with osteoblastic lesions
- Author
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Rogers, JS 2d, Spahr, J, Judge, DM, Varano, LA, and Eyster, ME
- Abstract
A 69-yr-old man with persistent anemia had multiple myeloma with an IgE- type kappa M component and Bence Jones proteinuria. Bone x-rays revealed occasional lytic lesions associated with a diffuse sclerotic reaction throughout the skeleton. Special bone histologic studies utilizing tetracycline labeling, undercalcified sections, and microradiography confirmed active osteoblastic activity. This case was compared with the four previously reported cases of IgE myeloma, one of which also had osteosclerosis.
- Published
- 1977
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9. Hydrazine-Catalysed Ring-Opening Metathesis Polymerization Of Cyclobutenes.
- Author
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Kellner-Rogers JS, Hsu JH, Keresztes I, Fors BP, and Lambert TH
- Abstract
Materials formed by the ring-opening metathesis polymerization (ROMP) of cyclic olefins are highly valued for industrial and academic applications but are difficult to prepare free of metal contaminants. Here we describe a highly efficient metal-free ROMP of cyclobutenes using hydrazine catalysis. Reactions can be initiated via in situ condensation of a [2.2.2]-bicyclic hydrazine catalyst with an aliphatic or aromatic aldehyde initiator. The polymerizations show living characteristics, achieving excellent control over molecular weight, low dispersity values, and high chain-end fidelity. Additionally, the hydrazine can be used in substoichiometric amounts relative to the aldehyde chain-end while maintaining good control over molecular weight and low dispersity values, indicating that a highly efficient chain transfer mechanism is occurring., (© 2024 Wiley-VCH GmbH.)
- Published
- 2024
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10. Diazene-Catalyzed Oxidative Alkyl Halide-Olefin Metathesis.
- Author
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Kellner-Rogers JS, Wang R, and Lambert TH
- Abstract
The first platform for oxidative alkyl halide-olefin metathesis is described. The procedure employs diazenes as catalysts, which effect the cyclization of alkenyl alkyl halides to generate cyclic olefins and carbonyl products. The synthesis of phenanthrene, coumarin, and quinolone derivatives is demonstrated as well as the potential to apply this strategy to other electrophiles.
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- 2024
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11. Design, synthesis, and evaluation of transition-state analogs as inhibitors of the bacterial quorum sensing autoinducer synthase CepI.
- Author
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Higgins EL, Kellner-Rogers JS, Estanislau AM, Esposito AC, Vail NR, Payne SR, Stockwell JG, and Ulrich SM
- Subjects
- Dose-Response Relationship, Drug, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Lactones chemical synthesis, Lactones chemistry, Ligases metabolism, Molecular Structure, Quorum Sensing drug effects, Structure-Activity Relationship, Drug Design, Enzyme Inhibitors pharmacology, Lactones pharmacology, Ligases antagonists & inhibitors
- Abstract
Quorum sensing is a bacterial signaling system that involves the synthesis, secretion and detection of signal molecules called autoinducers. The main autoinducer in Gram-negative bacteria are acylated homoserine lactones, produced by the LuxI family of autoinducer synthases and detected by the LuxR family of autoinducer receptors. Quorum sensing allows for changes in gene expression and bacterial behaviors in a coordinated, cell density dependent manner. Quorum sensing controls the expression of virulence factors in some human pathogens, making quorum sensing an antibacterial drug target. Here we describe the design and synthesis of transition-state analogs of the autoinducer synthase enzymatic reaction and the evaluation of these compounds as inhibitors of the synthase CepI. One such compound potently inhibits CepI and constitutes a new type of inhibitor against this underdeveloped antibacterial target., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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12. Targeting the ion channel TRPM7 promotes the thymic development of regulatory T cells by promoting IL-2 signaling.
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Mendu SK, Stremska ME, Schappe MS, Moser EK, Krupa JK, Rogers JS, Stipes EJ, Parker CA, Braciale TJ, Perry JSA, and Desai BN
- Subjects
- Animals, Female, Gene Deletion, Interleukin-2 genetics, Mice, Mice, Transgenic, Signal Transduction genetics, TRPM Cation Channels genetics, Thymus Gland growth & development, Interleukin-2 immunology, Signal Transduction immunology, T-Lymphocytes, Regulatory immunology, TRPM Cation Channels immunology, Thymus Gland immunology
- Abstract
The thymic development of regulatory T (T
reg ) cells, crucial suppressors of the responses of effector T (Teff ) cells, is governed by the transcription factor FOXP3. Despite the clinical importance of Treg cells, there is a dearth of druggable molecular targets capable of increasing their numbers in vivo. We found that inhibiting the function of the TRPM7 chanzyme (ion channel and enzyme) potentiated the thymic development of Treg cells in mice and led to a substantially higher frequency of functional Treg cells in the periphery. In addition, TRPM7-deficient mice were resistant to T cell-driven hepatitis. Deletion of Trpm7 and inhibition of TRPM7 channel activity by the FDA-approved drug FTY720 increased the sensitivity of T cells to the cytokine interleukin-2 (IL-2) through a positive feed-forward loop involving increased expression of the IL-2 receptor α-subunit and activation of the transcriptional regulator STAT5. Enhanced IL-2 signaling increased the expression of Foxp3 in thymocytes and promoted thymic Treg (tTreg ) cell development. Thus, these data indicate that inhibiting TRPM7 activity increases Treg cell numbers, suggesting that it may be a therapeutic target to promote immune tolerance., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)- Published
- 2020
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13. Author Correction: High frequency temperature variability reduces the risk of coral bleaching.
- Author
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Safaie A, Silbiger NJ, McClanahan TR, Pawlak G, Barshis DJ, Hench JL, Rogers JS, Williams GJ, and Davis KA
- Abstract
The original version of the Article was missing an acknowledgement of a funding source. The authors acknowledge that A. Safaie and K.Davis were supported by National Science Foundation Award No. 1436254 and G. Pawlak was supported by Award No. 1436522. This omission has now been corrected in the PDF and HTML versions of the Article.
- Published
- 2018
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14. A performance metric for screen selection with the acoustic single pixel imager.
- Author
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Ramirez J Jr, Rogers JS, and Edelmann GF
- Abstract
In the recent literature, an Acoustic Single-Pixel Imager has been successfully developed for source localization in a two-dimensional waveguide. Source bearing angle estimation was carried out by applying sparse recovery techniques on sensor measurements taken over different imaging screens. This paper shows that the Mutual Coherence of the sensing matrix can be used as a metric to predict the source localization capability of the single-pixel imaging system. In particular, this paper's analysis focuses on the sparsity of open cells within the imaging screen and the number of imaging screens used to maximize the probability of correct detection over varying levels of source sparsity. In this work, a simulation environment to demonstrate how the mutual coherence of the sensing matrix correlates with source localization performance over source sparsity, sparsity of open screen cells, and number of measurements used for sparse recovery is developed. The analysis shows that the leading factor in source localization performance gains is primarily from the number of imaging screens used to measure the acoustic wave-field.
- Published
- 2018
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15. Exploiting platform motion for passive source localization with a co-prime sampled large aperture array.
- Author
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Ramirez J Jr and Rogers JS
- Abstract
Co-prime array geometries have received a great deal of attention due to their ability to discriminate O(MN) sources with only O(M + N) sensors. This has been demonstrated both theoretically and in simulation. However, there are many practical limitations that make it difficult to realize the enhanced degrees of freedom when applying co-prime geometries to real acoustic data taken on a horizontal line array. For instance, co-prime sampling leads to grating lobes that can obscure lower signal-to-noise-ratio acoustic signals making them difficult to detect. In this work, a synthetic aperture (SA) method is presented for filling in holes and increasing redundancy in the difference co-array by exploiting array motion. The SA method is applied to acoustic data collected off the Southeastern shore of Florida on a fixed large aperture horizontal array. Array motion is simulated by taking a co-prime sampled subarray and virtually moving it along the horizontal aperture of the fixed array. It is demonstrated that SA processing on real acoustic data results in reduced side-lobe and grating lobe levels compared to that of the physical co-prime aperture.
- Published
- 2018
- Full Text
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16. High frequency temperature variability reduces the risk of coral bleaching.
- Author
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Safaie A, Silbiger NJ, McClanahan TR, Pawlak G, Barshis DJ, Hench JL, Rogers JS, Williams GJ, and Davis KA
- Subjects
- Animals, Coral Reefs, Ecosystem, Hot Temperature, Seasons, Seawater chemistry, Symbiosis, Anthozoa physiology, Chlorophyta physiology
- Abstract
Coral bleaching is the detrimental expulsion of algal symbionts from their cnidarian hosts, and predominantly occurs when corals are exposed to thermal stress. The incidence and severity of bleaching is often spatially heterogeneous within reef-scales (<1 km), and is therefore not predictable using conventional remote sensing products. Here, we systematically assess the relationship between in situ measurements of 20 environmental variables, along with seven remotely sensed SST thermal stress metrics, and 81 observed bleaching events at coral reef locations spanning five major reef regions globally. We find that high-frequency temperature variability (i.e., daily temperature range) was the most influential factor in predicting bleaching prevalence and had a mitigating effect, such that a 1 °C increase in daily temperature range would reduce the odds of more severe bleaching by a factor of 33. Our findings suggest that reefs with greater high-frequency temperature variability may represent particularly important opportunities to conserve coral ecosystems against the major threat posed by warming ocean temperatures.
- Published
- 2018
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17. Beamforming using chip-scale atomic clocks in a controlled environment.
- Author
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Freeman SE, Emokpae L, Rogers JS, and Edelmann GF
- Abstract
Recently developed low-power Chip-Scale Atomic Clocks (CSACs) hold promise for underwater acoustics applications because they enable time-coherent processing, critical for estimating the directionality of the sound field, when acoustic array elements cannot share a timing reference. Controlled, tank-based experiments with a small acoustic array (N = 4) featuring CSAC-equipped elements show that optimal disciplining is important for continued array coherence. Clock drift equivalent to a 10% wavelength error at 0.3, 1, and 10 kHz was reached at approximately 25, 10, and 3 days, respectively. Within application-specific limits, this technology brings enhanced capabilities to acoustic thermometry, geoacoustic, biological, and under-ice acoustic oceanography.
- Published
- 2018
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18. Chanzyme TRPM7 Mediates the Ca 2+ Influx Essential for Lipopolysaccharide-Induced Toll-Like Receptor 4 Endocytosis and Macrophage Activation.
- Author
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Schappe MS, Szteyn K, Stremska ME, Mendu SK, Downs TK, Seegren PV, Mahoney MA, Dixit S, Krupa JK, Stipes EJ, Rogers JS, Adamson SE, Leitinger N, and Desai BN
- Subjects
- Animals, Cell Culture Techniques, Endocytosis drug effects, Female, Flow Cytometry, Fluorescent Antibody Technique, Gene Expression Regulation, Genotyping Techniques, Immunoblotting, Interferon Regulatory Factor-3 metabolism, Lipopolysaccharides pharmacology, Macrophages metabolism, Male, Mice, NF-kappa B metabolism, Patch-Clamp Techniques, Real-Time Polymerase Chain Reaction, Signal Transduction drug effects, Signal Transduction physiology, TRPM Cation Channels genetics, Calcium metabolism, Macrophage Activation drug effects, TRPM Cation Channels metabolism, Toll-Like Receptor 4 metabolism
- Abstract
Toll-like receptors (TLRs) sense pathogen-associated molecular patterns to activate the production of inflammatory mediators. TLR4 recognizes lipopolysaccharide (LPS) and drives the secretion of inflammatory cytokines, often contributing to sepsis. We report that transient receptor potential melastatin-like 7 (TRPM7), a non-selective but Ca
2+ -conducting ion channel, mediates the cytosolic Ca2+ elevations essential for LPS-induced macrophage activation. LPS triggered TRPM7-dependent Ca2+ elevations essential for TLR4 endocytosis and the subsequent activation of the transcription factor IRF3. In a parallel pathway, the Ca2+ signaling initiated by TRPM7 was also essential for the nuclear translocation of NFκB. Consequently, TRPM7-deficient macrophages exhibited major deficits in the LPS-induced transcriptional programs in that they failed to produce IL-1β and other key pro-inflammatory cytokines. In accord with these defects, mice with myeloid-specific deletion of Trpm7 are protected from LPS-induced peritonitis. Our study highlights the importance of Ca2+ signaling in macrophage activation and identifies the ion channel TRPM7 as a central component of TLR4 signaling., (Copyright © 2017 Elsevier Inc. All rights reserved.)- Published
- 2018
- Full Text
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19. Ambient noise forecasting with a large acoustic array in a complex shallow water environment.
- Author
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Rogers JS, Wales SC, and Means SL
- Abstract
Forecasting ambient noise levels in the ocean can be a useful way of characterizing the detection performance of sonar systems and projecting bounds on performance into the near future. The assertion is that noise forecasting can be improved with a priori knowledge of source positions coupled with the ability to resolve closely separated sources in bearing. One example of such a system is the large aperture research array located at the South Florida Test Facility. Given radar and Automatic Identification System defined source positions and environmental information, transmission loss (TL) is computed from known source positions to the array. Source levels (SLs) of individual ships are then estimated from computed TL and the pre-determined beam response of the array using a non-negative least squares algorithm. Ambient noise forecasts are formed by projecting the estimated SLs along known ship tracks. Ambient noise forecast estimates are compared to measured beam level data and mean-squared error is computed. A mean squared error as low as 3.5 dB is demonstrated in 30 min forecast estimates when compared to ground truth.
- Published
- 2017
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20. Evaluation of the resolution of a metamaterial acoustic leaky wave antenna.
- Author
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Naify CJ, Rogers JS, Guild MD, Rohde CA, and Orris GJ
- Abstract
Acoustic antennas have long been utilized to directionally steer acoustic waves in both air and water. Typically, these antennas are comprised of arrays of active acoustic elements, which are electronically phased to steer the acoustic profile in the desired direction. A new technology, known as an acoustic leaky wave antenna (LWA), has recently been shown to achieve directional steering of acoustic waves using a single active transducer coupled to a transmission line passive aperture. The LWA steers acoustic energy by preferential coupling to an input frequency and can be designed to steer from backfire to endfire, including broadside. This paper provides an analysis of resolution as a function of both input frequency and antenna length. Additionally, the resolution is compared to that achieved using an array of active acoustic elements.
- Published
- 2016
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21. Acetylfentanyl: An Emerging Drug of Abuse.
- Author
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Rogers JS, Rehrer SJ, and Hoot NR
- Subjects
- Adult, Fentanyl poisoning, Humans, Male, Analgesics, Opioid poisoning, Fentanyl analogs & derivatives, Psychotropic Drugs poisoning, Respiratory Insufficiency chemically induced, Substance-Related Disorders etiology
- Abstract
Background: Opioid analgesics are widely used in health care, yet have significant potential for abuse. High doses are associated with potentially fatal respiratory depression, which caused 21,314 deaths in the United States in 2011. Acetylfentanyl, a synthetic opioid agonist closely related to fentanyl, recently emerged as a drug of abuse linked to numerous deaths in North America., Case Report: A 36-year-old male developed the habit of using a propylene glycol electronic cigarette filled with acetylfentanyl to aid relaxation. He purchased the drug online in a manner that appeared legal to him, which compromised his insight about the danger of the substance. He had been using the e-cigarette with increasing frequency while on medical leave, and his wife reported finding him weakly responsive on more than one occasion. At approximately 3 am, the family activated 911 for altered mental status. His presentation included respiratory depression, pinpoint pupils, hypoxemia, and a Glasgow Coma Scale score of 6. He responded to serial doses of intravenous naloxone with improvement in his mental status and respiratory condition. Due to the need for repeated dosing, he was placed on a naloxone infusion and recovered uneventfully in intensive care. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Complications from emerging drugs of abuse, like acetylfentanyl, frequently present first to emergency departments. Prompt recognition and treatment can help avoid morbidity and mortality. Acetylfentanyl can be managed effectively with naloxone, although higher than conventional dosing may be required to achieve therapeutic effect., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
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22. Randomized, double-blind, placebo-controlled, multicenter phase II study of the efficacy and safety of apricoxib in combination with either docetaxel or pemetrexed in patients with biomarker-selected non-small-cell lung cancer.
- Author
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Edelman MJ, Tan MT, Fidler MJ, Sanborn RE, Otterson G, Sequist LV, Evans TL, Schneider BJ, Keresztes R, Rogers JS, de Mayolo JA, Feliciano J, Yang Y, Medeiros M, and Zaknoen SL
- Subjects
- Aged, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung urine, Cyclooxygenase 2 metabolism, Disease-Free Survival, Docetaxel, Double-Blind Method, Drug Administration Schedule, Female, Glutamates administration & dosage, Guanine administration & dosage, Guanine analogs & derivatives, Humans, Kaplan-Meier Estimate, Lung Neoplasms pathology, Lung Neoplasms urine, Male, Middle Aged, Neoplasm Staging, Patient Selection, Pemetrexed, Pyrroles administration & dosage, Pyrroles adverse effects, Sulfonamides administration & dosage, Sulfonamides adverse effects, Taxoids administration & dosage, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor urine, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, Prostaglandins urine
- Abstract
Purpose: Overexpression of COX-2 correlates with advanced stage and worse outcomes in non-small-cell lung cancer (NSCLC), possibly as a result of elevated levels of COX-2-dependent prostaglandin E2 (PGE2). Exploratory analyses of studies that used COX-2 inhibitors have demonstrated potentially superior outcome in patients in whom the urinary metabolite of PGE2 (PGE-M) is suppressed. We hypothesized that patients with disease defined by PGE-M suppression would benefit from the addition of apricoxib to second-line docetaxel or pemetrexed., Patients and Methods: Patients with NSCLC who had disease progression after one line of platinum-based therapy, performance status of 0 to 2, and normal organ function were potentially eligible. Only patients with a ≥ 50% decrease in urinary PGE-M after 5 days of treatment with apricoxib could enroll. Docetaxel 75 mg/m(2) or pemetrexed 500 mg/m(2) once every 21 days per the investigator was administered with apricoxib or placebo 400 mg once per day. The primary end point was progression-free survival (PFS). Exploratory analysis was performed regarding baseline urinary PGE-M and outcomes., Results: In all, 101 patients completed screening, and 72 of the 80 who demonstrated ≥ 50% suppression were randomly assigned to apricoxib or placebo. Toxicity was similar between the arms. No improvement in PFS was seen with apricoxib versus placebo. The median PFS for the control arm was 97 days (95% CI, 52 to 193 days) versus 85 days (95% CI, 67 to 142 days) for the experimental arm (P = .91)., Conclusion: Apricoxib did not improve PFS, despite biomarker-driven patient selection., (© 2014 by American Society of Clinical Oncology.)
- Published
- 2015
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23. Interferon alpha plus 13-cis-retinoic acid modulation of BCL-2 plus paclitaxel for recurrent small-cell lung cancer (SCLC): an Eastern Cooperative Oncology Group study (E6501).
- Author
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Pillai RN, Aisner J, Dahlberg SE, Rogers JS, DiPaola RS, Aisner S, Ramalingam SS, and Schiller JH
- Subjects
- Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Biomarkers blood, Carcinoma, Small Cell blood, Carcinoma, Small Cell drug therapy, Chemotherapy-Induced Febrile Neutropenia physiopathology, Cohort Studies, Early Termination of Clinical Trials, Female, Follow-Up Studies, Humans, Interferon-alpha administration & dosage, Interferon-alpha adverse effects, Isotretinoin administration & dosage, Isotretinoin adverse effects, Leukocytes, Mononuclear metabolism, Leukopenia chemically induced, Leukopenia physiopathology, Lung Neoplasms blood, Lung Neoplasms drug therapy, Male, Middle Aged, Neoplasm Recurrence, Local blood, Paclitaxel administration & dosage, Paclitaxel adverse effects, Proto-Oncogene Proteins c-bcl-2 blood, Severity of Illness Index, Small Cell Lung Carcinoma blood, Survival Analysis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Interferon-alpha therapeutic use, Isotretinoin therapeutic use, Neoplasm Recurrence, Local drug therapy, Paclitaxel therapeutic use, Proto-Oncogene Proteins c-bcl-2 antagonists & inhibitors, Small Cell Lung Carcinoma drug therapy
- Abstract
Background: Patients with recurrent small-cell lung cancer (SCLC) have dismal outcomes. The failure of salvage therapy is due to the possible development of resistance mechanisms, such as the upregulation of the anti-apoptosis protein, Bcl-2. We conducted a phase II study to evaluate if modulation of Bcl-2 with 13-cis-retinoic acid (13-CRA) and interferon alpha could improve response rates when combined with paclitaxel in patients with recurrent SCLC., Methods: Patients with recurrent SCLC and measurable disease were treated with interferon alpha at 6 million units/m² subcutaneously and 13-CRA 1 mg/kg orally on days 1 and 2 and paclitaxel 75 mg/m² intravenously on day 2 of each week for 6 weeks of an 8-week treatment cycle. Treatment was continued until disease progression, development of unacceptable toxicity, or withdrawal of consent. The primary endpoint was response rate with secondary endpoints of progression-free survival (PFS) and overall survival (OS). Bcl-2 levels were assessed in peripheral blood mononuclear cells (PBMCs)., Results: Thirty-seven patients were enrolled; 34 were included in the intention-to-treat analysis as 3 patients were ineligible for the study. There were 3 partial responses (9 %), and 5 patients had stable disease (15 %) as best response. The median PFS was 2 months, and median OS was 6.2 months. Although mean Bcl-2 protein levels decreased with therapy in PBMCs, there was no association between Bcl-2 levels and response rate or survival., Conclusion: Despite sound pre-clinical evidence, the addition of 13-CRA and interferon alpha to paclitaxel did not improve outcomes for recurrent SCLC.
- Published
- 2014
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24. Slowed Dynamics of Thin Filament Regulatory Units Reduces Ca 2+ -Sensitivity of Cardiac Biomechanical Function.
- Author
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Loong CK, Takeda AK, Badr MA, Rogers JS, and Chase PB
- Abstract
Actomyosin kinetics in both skinned skeletal muscle fibers at maximum Ca
2+ -activation and unregulated in vitro motility assays are modulated by solvent microviscosity in a manner consistent with a diffusion limited process. Viscosity might also influence cardiac thin filament Ca2+ -regulatory protein dynamics. In vitro motility assays were conducted using thin filaments reconstituted with recombinant human cardiac troponin and tropomyosin; solvent microviscosity was varied by addition of sucrose or glucose. At saturating Ca2+ , filament sliding speed ( s ) was inversely proportional to viscosity. Ca2+ -sensitivity ( pCa50 ) of s decreased markedly with elevated viscosity ( η/η0 ≥ ~1.3). For comparison with unloaded motility assays, steady-state isometric force ( F ) and kinetics of isometric tension redevelopment ( kTR ) were measured in single, permeabilized porcine cardiomyocytes when viscosity surrounding the myofilaments was altered. Maximum Ca2+ -activated F changed little for sucrose ≤ 0.3 M ( η/η0 ~1.4) or glucose ≤ 0.875 M ( η/η0 ~1.66), but decreased at higher concentrations. Sucrose (0.3 M) or glucose (0.875 M) decreased pCa50 for F . kTR at saturating Ca2+ decreased steeply and monotonically with increased viscosity but there was little effect on kTR at sub-maximum Ca2+ . Modeling indicates that increased solutes affect dynamics of cardiac muscle Ca2+ -regulatory proteins to a much greater extent than actomyosin cross-bridge cycling.- Published
- 2013
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25. Maximum-likelihood spatial spectrum estimation in dynamic environments with a short maneuverable array.
- Author
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Odom JL, Krolik JL, and Rogers JS
- Subjects
- Algorithms, Bayes Theorem, Computer Simulation, Equipment Design, Likelihood Functions, Monte Carlo Method, Motion, Numerical Analysis, Computer-Assisted, ROC Curve, Signal-To-Noise Ratio, Sound Spectrography, Time Factors, Acoustics instrumentation, Models, Theoretical, Signal Processing, Computer-Assisted, Sound
- Abstract
This work concerns the development of field directionality mapping algorithms for short acoustic arrays on mobile maneuverable platforms that avoid the left/right ambiguities and endfire resolution degradation common to longer non-maneuverable line arrays. In this paper, it is shown that short maneuverable arrays can achieve a high fraction of usable bearing space for target detection in interference-dominated scenarios, despite their lower array gain against diffuse background noise. Two narrowband techniques are presented which use the expectation-maximization maximum likelihood algorithm under different models of the time-varying field directionality. The first, derivative based maximum likelihood, uses a deterministic model while the second, recursive Bayes maximum likelihood, uses a stochastic model for the time-varying spatial spectrum. In addition, a broadband extension is introduced that incorporates temporal spectral knowledge to suppress ambiguities when the average sensor array spacing is greater than a half-wavelength. Dynamic multi-source simulations demonstrate the ability of a short, maneuvering array to reduce array ambiguities and spatial grating lobes in an interference dominated environment. Monte Carlo evaluation of receiver operating characteristics is used to evaluate the improvement in source detection achieved by the proposed methods versus conventional broadband beamforming.
- Published
- 2013
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26. Pantoea species sepsis associated with sickle cell crisis in a pregnant woman with a history of pica.
- Author
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Achkar MA, Rogers JS, and Muszynski MJ
- Abstract
Background: Bacteria in the Pantoea genus are plant and soil associated Gram-negative rods described as nosocomial pathogens and as rare causes of community-acquired infections. The latter have been classically associated with gardening and plant thorn injuries and immunocompromised states are additional risk factors. We report a patient with pica and geophagia, Pantoea sepsis, and sickle cell crisis, associations not previously described., Case Report: A 23-year-old pregnant female presented to the emergency department with sickle cell pain crisis. On the third day of hospitalization the patient developed fever subsequently determined to be caused by Pantoea bacteremia and sepsis. She was successfully treated with a two-week course of ceftriaxone. The patient admitted to a habit of frequently eating large amounts of soil and this geophagia had increased since she became pregnant. She had marked clinical improvement with treatment and she was counseled to stop eating soil., Conclusions: This is the first reported case of Pantoea infection possibly associated with geophagia and the first reported case of Pantoea bacteremia and sepsis related to an episode of sickle cell crisis.
- Published
- 2012
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27. Time-varying spatial spectrum estimation with a maneuverable towed array.
- Author
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Rogers JS and Krolik JL
- Subjects
- Algorithms, Computer Simulation, Least-Squares Analysis, Likelihood Functions, Motion, ROC Curve, Sound, Sound Spectrography, Time Factors, Acoustics instrumentation, Models, Theoretical, Radar instrumentation, Ships, Signal Processing, Computer-Assisted
- Abstract
This paper addresses the problem of field directionality mapping (FDM) or spatial spectrum estimation in dynamic environments with a maneuverable towed acoustic array. Array processing algorithms for towed arrays are typically designed assuming the array is straight, and are thus degraded during tow-ship maneuvers. In this paper, maneuvering the array is treated as a feature allowing for left and right disambiguation as well as improved resolution toward endfire. The Cramér-Rao lower bound is used to motivate the improvement in source localization which can be theoretically achieved by exploiting array maneuverability. Two methods for estimating time-varying field directionality with a maneuvering array are presented: (1) Maximum likelihood (ML) estimation solved using the expectation maximization algorithm and (2) a non-negative least squares (NNLS) approach. The NNLS method is designed to compute the field directionality from beamformed power outputs, while the ML algorithm uses raw sensor data. A multi-source simulation is used to illustrate both the proposed algorithms' ability to suppress ambiguous towed array backlobes and resolve closely spaced interferers near endfire which pose challenges for conventional beamforming approaches especially during array maneuvers. Receiver operating characteristics are presented to evaluate the algorithms' detection performance versus signal-to-noise ratio. The results indicate that both FDM algorithms offer the potential to provide superior detection performance when compared to conventional beamforming with a maneuverable array.
- Published
- 2010
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28. Computational prediction and experimental verification of new MAP kinase docking sites and substrates including Gli transcription factors.
- Author
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Whisenant TC, Ho DT, Benz RW, Rogers JS, Kaake RM, Gordon EA, Huang L, Baldi P, and Bardwell L
- Subjects
- Binding Sites, Genome, Human, Humans, Kruppel-Like Transcription Factors chemistry, Nerve Tissue Proteins chemistry, Protein Binding, Substrate Specificity, Transcription Factors chemistry, Zinc Finger Protein GLI1, Zinc Finger Protein Gli3, Algorithms, Artificial Intelligence, Knowledge Bases, Mitogen-Activated Protein Kinases chemistry
- Abstract
In order to fully understand protein kinase networks, new methods are needed to identify regulators and substrates of kinases, especially for weakly expressed proteins. Here we have developed a hybrid computational search algorithm that combines machine learning and expert knowledge to identify kinase docking sites, and used this algorithm to search the human genome for novel MAP kinase substrates and regulators focused on the JNK family of MAP kinases. Predictions were tested by peptide array followed by rigorous biochemical verification with in vitro binding and kinase assays on wild-type and mutant proteins. Using this procedure, we found new 'D-site' class docking sites in previously known JNK substrates (hnRNP-K, PPM1J/PP2Czeta), as well as new JNK-interacting proteins (MLL4, NEIL1). Finally, we identified new D-site-dependent MAPK substrates, including the hedgehog-regulated transcription factors Gli1 and Gli3, suggesting that a direct connection between MAP kinase and hedgehog signaling may occur at the level of these key regulators. These results demonstrate that a genome-wide search for MAP kinase docking sites can be used to find new docking sites and substrates.
- Published
- 2010
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29. Conjugated linoleic acids modulate UVR-induced IL-8 and PGE2 in human skin cells: potential of CLA isomers in nutritional photoprotection.
- Author
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Storey A, Rogers JS, McArdle F, Jackson MJ, and Rhodes LE
- Subjects
- Adult, Cell Line, Tumor, Dinoprostone radiation effects, Female, Humans, Interleukin-8 metabolism, Interleukin-8 radiation effects, Isomerism, Keratinocytes drug effects, Keratinocytes metabolism, Keratinocytes radiation effects, Male, Middle Aged, Skin cytology, Skin drug effects, Skin metabolism, Dinoprostone metabolism, Interleukin-8 biosynthesis, Linoleic Acids, Conjugated physiology, Skin radiation effects, Ultraviolet Rays
- Abstract
Conjugated linoleic acids (CLA), derivatives of linoleic acid found in food products, inhibit chemically induced skin cancers in mice. However, their potential photoprotective properties remain unexplored. We examined whether CLA may modulate ultraviolet radiation (UVR)-induced secretion of interleukin (IL)-8 and prostaglandin E2 (PGE(2)), mediators implicated in UVR-induced inflammation and carcinogenesis, in human skin cells. Since tumour necrosis factor (TNF)-alpha is an early mediator of UVR effects, we also examined influence of CLA on TNF-alpha-induced mediator release. HaCaT keratinocytes were supplemented with CLA isomers cis-9-trans-11 (c9,t11-CLA; > or =90%), trans-10-cis-12 (t10,c12-CLA; > or =90%) or all trans-trans isomers (tt-CLA; 23.7%) in tetrahydrofuran/fetal calf serum (THF/FCS) or THF/FCS control. Supplementation of keratinocytes with c9,t11-CLA reduced Ultraviolet B(UVB)-induced IL-8 from 37 113 +/- 2903 pg/ng protein in control cells to 14 167 +/- 2063 pg/ng protein (P < 0.001). Similarly, t10,c12-CLA reduced UVB-induced IL-8 to 9786 +/- 1291.5 pg/ng protein (P < 0.001). Additionally, t10,c12-CLA and tt-CLA inhibited TNF-alpha-induced IL-8 from 11 669 +/- 1692 pg/ng protein in control cells to 5540 +/- 191 (P < 0.001) and 8082 +/- 1298 pg/ng (P < 0.01) protein, respectively. UVB-induced PGE(2) release was reduced by tt-CLA supplementation, from 4.8 +/- 1.2 to 1.6 +/- 0.8 pg/mg protein (P < 0.01), but increased by t10,c12-CLA to 8.8 +/- 1 pg/mg protein (P < 0.001). Influence of CLA on UVB-induced PGE(2) release was further explored in CCD922SK dermal fibroblasts. CLA isomers reduced UVB-induced PGE(2) in fibroblasts, reaching significance with c9,t11-CLA (98 +/- 5 falling to 0 pg/mg protein, P < 0.05). Hence, CLA isomers differentially modulate UVB effects on skin cells in vitro. CLA-containing foods have potential in photoprotection; the cutaneous effects of individual isomers warrant clinical study.
- Published
- 2007
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30. Increased scalp skin lipids in response to antidandruff treatment containing zinc pyrithione.
- Author
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Rogers JS, Moore AE, Meldrum H, and Harding CR
- Subjects
- Ceramides metabolism, Epidermis metabolism, Humans, Dermatomycoses drug therapy, Dermatomycoses metabolism, Keratolytic Agents therapeutic use, Lipid Metabolism, Malassezia, Organometallic Compounds therapeutic use, Pyridines therapeutic use, Scalp metabolism
- Published
- 2003
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31. Clinical role of F-18 fluorodeoxyglucose positron emission tomography imaging in patients with lung cancer and suspected malignant pleural effusion.
- Author
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Gupta NC, Rogers JS, Graeber GM, Gregory JL, Waheed U, Mullet D, and Atkins M
- Subjects
- Diagnosis, Differential, Female, Humans, Male, Middle Aged, Pleural Effusion diagnostic imaging, Pleural Neoplasms diagnosis, Predictive Value of Tests, Sensitivity and Specificity, Tomography, X-Ray Computed, Fluorodeoxyglucose F18, Lung Neoplasms diagnostic imaging, Pleural Effusion, Malignant diagnostic imaging, Radiopharmaceuticals, Tomography, Emission-Computed
- Abstract
Study Objectives: The goals of this study were to determine the sensitivity, specificity, and predictive accuracy of F-18 fluorodeoxyglucose positron emission tomography (PET-FDG) imaging in detecting metastatic disease involvement of pleura and/or presence of malignant pleural effusion in patients with proven lung cancer. We wanted to compare efficacy of PET-FDG imaging to CT scanning in differentiating benign pleural effusion from malignant effusion and/or pleural involvement in patients with lung cancer., Methods: We studied 35 patients with biopsy-proven lung cancer and abnormal findings on CT scanning for presence of pleural effusion (n = 34) and/or pleural thickening or nodular involvement (n = 4). The results of positron emission tomography and CT scanning were compared to pleural cytology (n = 31), histologic findings of pleural biopsy (n = 3), and/or clinical follow-up (n = 3) for at least 1 year for presence or absence of malignant pleural effusion., Results: PET-FDG imaging correctly detected the presence of malignant pleural effusion and malignant pleural involvement in 16 of 18 patients and excluded malignant effusion or pleural metastatic involvement in 16 of 17 patients (sensitivity, specificity, and accuracy of 88.8%, 94.1%, and 91.4% respectively)., Conclusion: PET-FDG imaging is a highly accurate and reliable noninvasive test to differentiate malignant from benign pleural effusion and/or pleural involvement in patients with lung cancer and findings of suspected malignant pleural effusion on CT scanning.
- Published
- 2002
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32. Dandruff: a condition characterized by decreased levels of intercellular lipids in scalp stratum corneum and impaired barrier function.
- Author
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Harding CR, Moore AE, Rogers JS, Meldrum H, Scott AE, and McGlone FP
- Subjects
- Administration, Cutaneous, Adult, Case-Control Studies, Cholesterol metabolism, Dermatitis, Seborrheic etiology, Epidermis drug effects, Epidermis metabolism, Ethnicity, Fatty Acids metabolism, Fatty Acids, Nonesterified metabolism, Female, Histamine administration & dosage, Humans, Male, Permeability, Pruritus etiology, Scalp drug effects, Scalp metabolism, Scalp Dermatoses etiology, Thailand, United Kingdom, Dermatitis, Seborrheic metabolism, Lipid Metabolism, Scalp Dermatoses metabolism
- Abstract
Dandruff is a major problem, yet little is known about the underlying mechanism and subsequent biochemical changes occurring in the scalp skin that lead to its manifestation. The characteristic flaking and scaling of the scalp experienced by dandruff sufferers suggests, similar to the changes classically seen in xerosis, that the desquamation process is impaired. We initiated studies to quantify the biochemical nature of the stratum corneum in the scalp of healthy individuals and dandruff sufferers. Total amounts and relative ratios of stratum corneum lipids species were analysed in scalp stratum corneum samples collected during studies conducted in the UK and Thailand in order to examine ethnic differences. In both populations, dandruff was associated with a dramatic decrease in free lipid levels, with significant decreases in ceramides, fatty acids, and cholesterol. Detailed sub-analysis of the major ceramide species within the total ceramide fraction revealed a decrease in ceramide 1 and increased proportions of ceramide 6i and 6ii. In a separate study, we demonstrated that dandruff sufferers show both an elevated blood flow and an increased reported incidence of itch in response to histamine topically applied to the scalp compared with no-dandruff controls. Taken together these two studies indicate that the quality and resilience of the epidermal water barrier is impaired in the scalp of dandruff sufferers. We propose that the perturbed barrier leaves dandruff sufferers more prone to the adverse effects of microbial and fungal toxins, and environmental pollutants, thus perpetuating their impaired barrier.
- Published
- 2002
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33. The effect of conjugated linoleic acid on arachidonic acid metabolism and eicosanoid production in human saphenous vein endothelial cells.
- Author
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Urquhart P, Parkin SM, Rogers JS, Bosley JA, and Nicolaou A
- Subjects
- Arachidonic Acid biosynthesis, Arachidonic Acid chemistry, Calcimycin antagonists & inhibitors, Carbon Radioisotopes, Cells, Cultured, Cyclooxygenase 1, Docosahexaenoic Acids pharmacology, Dose-Response Relationship, Drug, Eicosapentaenoic Acid pharmacology, Fatty Acids, Unsaturated pharmacology, Humans, Isoenzymes biosynthesis, Linoleic Acid chemistry, Membrane Lipids biosynthesis, Membrane Lipids chemistry, Membrane Proteins, Phospholipids biosynthesis, Prostaglandin-Endoperoxide Synthases biosynthesis, Prostaglandins biosynthesis, Saphenous Vein, Stereoisomerism, Thromboxanes biosynthesis, Arachidonic Acid metabolism, Endothelium, Vascular metabolism, Linoleic Acid pharmacology
- Abstract
The effects of a conjugated linoleic acid (CLA) mixture of single isomers (50:50, w/w, cis9,trans11:trans10,cis12) and the individual isomers on (a) the production of resting and calcium ionophore stimulated (14)C-eicosanoids and (b) the incorporation of (14)C-arachidonic acid (AA) into membrane phospholipids of human saphenous vein endothelial cells were investigated. The CLA mixture and the individual isomers were found to inhibit resting production of (14)C-prostaglandin F(2a) by 50, 43 and 40%, respectively. A dose dependent inhibition of stimulated (14)C-prostaglandins was observed with the CLA mixture (IC(50) 100 microM). The cis9,trans11 and trans10,cis12 (50 microM) isomers individually inhibited the overall production of stimulated (14)C-prostaglandins (between 35 and 55% and 23 and 42%, respectively). When tested at a high concentration (100 microM), cis9,trans11 was found to inhibit eicosanoid production in contrast to trans10,cis12 that caused stimulation. The overall degree of (14)C-AA incorporation into membrane phospholipids of the CLA (mixture and individual isomers) treated cells was found to be lower than that of control cells and the cis9,trans11 isomer was found to increase the incorporation of (14)C-AA into phosphatidylcholine. Docosahexaenoic acid, eicosapentaenoic acid and linoleic acid did not alter the overall degree of incorporation of (14)C-AA. The results of this study suggest that both isomers inhibit eicosanoid production, and although trans10,cis12 exhibits pro-inflammatory activity at high concentrations, the CLA mixture maintains its beneficial anti-inflammatory action that contributes to its anti-carcinogenic and anti-atherogenic properties.
- Published
- 2002
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34. Maximum likelihood estimation of phylogenetic trees is consistent when substitution rates vary according to the invariable sites plus gamma distribution.
- Author
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Rogers JS
- Subjects
- Base Sequence, Likelihood Functions, Models, Statistical, Models, Genetic, Phylogeny
- Abstract
Maximum likelihood estimation of phylogenetic trees from nucleotide sequences is completely consistent when nucleotide substitution is governed by the general time reversible (GTR) model with rates that vary over sites according to the invariable sites plus gamma (I + gamma) distribution.
- Published
- 2001
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35. Clinical utility of PET-FDG imaging in differentiation of benign from malignant adrenal masses in lung cancer.
- Author
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Gupta NC, Graeber GM, Tamim WJ, Rogers JS, Irisari L, and Bishop HA
- Abstract
This study was designed to evaluate the sensitivity, specificity, and predictive accuracy of PET-FDG imaging in detecting metastatic disease involvement of adrenal glands in patients with lung cancer. We wanted to compare efficacy of positron emission tomography (PET)-fluorodeoxyglucose (FDG) imaging to computed tomography (CT) scanning in differentiating benign from malignant involvement of adrenal glands in patients with lung cancer. Thirty patients with biopsy-proven lung cancer and abnormal findings on PET and/or CT scanning were studied for presence of adrenal abnormality suggestive of metastatic disease involvement (n = 26) or benign adrenal enlargement (n = 4). The results of PET and CT scanning were compared to histological findings and/or clinical follow-up for at least 1 year for presence or absence of adrenal metastases. PET-FDG imaging correctly detected the presence of metastatic involvement in 17 of 18 patients and excluded metastatic involvement in 11 of 12 patients for sensitivity, specificity, and accuracy of 94.4%, 91.6%, and 93.3%, respectively. CT scanning showed enlarged adrenals without metastases in 8 of 30 patients and normal-sized adrenals in the presence of metastases in 5 of 30 patients. There was a false-positive PET finding in 1 patient and a false-negative PET finding in another patient. PET-FDG imaging is a highly sensitive, specific, and accurate test to differentiate benign from malignant involvement of adrenal glands in patients with lung cancer and often ambiguous findings on CT scanning.
- Published
- 2001
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- View/download PDF
36. Bias in phylogenetic estimation and its relevance to the choice between parsimony and likelihood methods.
- Author
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Swofford DL, Waddell PJ, Huelsenbeck JP, Foster PG, Lewis PO, and Rogers JS
- Subjects
- Bias, Likelihood Functions, Models, Genetic, Models, Statistical, Stochastic Processes, Phylogeny
- Published
- 2001
37. A phase II trial of 6-hydroxymethylacylfulvene (MGI-114, irofulven) in patients with advanced non-small cell cancer previously treated with chemotherapy.
- Author
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Dowell JE, Johnson DH, Rogers JS, Shyr Y, McCullough N, Krozely P, and DeVore RF
- Subjects
- Aged, Aged, 80 and over, Anemia chemically induced, Antineoplastic Agents, Alkylating adverse effects, Antineoplastic Agents, Alkylating therapeutic use, Drug Evaluation, Fatigue chemically induced, Female, Humans, Male, Middle Aged, Nausea chemically induced, Neutropenia chemically induced, Sesquiterpenes adverse effects, Sesquiterpenes therapeutic use, Thrombocytopenia chemically induced, Toxicity Tests, Treatment Outcome, Vomiting chemically induced, Antineoplastic Agents, Alkylating administration & dosage, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, Sesquiterpenes administration & dosage
- Abstract
Purpose: To test the efficacy and safety of the novel antitumor agent MGI-114 (NSC 683863) in patients with advanced non-small cell lung cancer (NSCLC) previously treated with chemotherapy., Methods: A two-stage accrual design was used to ensure detection of a true response rate of at least 20% with a type I error of .04. Eligible patients received 11 mg/m2 daily for five consecutive days. Cycles were repeated every 28 days., Results: Fifteen patients received a total of 34 cycles of MGI-114. All patients had a performance status of 0 or 1. Eleven patients had previously received carboplatin and paclitaxel +/- radiation. Two patients had received cisplatin and CPT-11, one patient had received weekly paclitaxel, and one patient had received carboplatin and docetaxel. None of the first 15 patients enrolled experienced objective tumor response, and the study was closed. Forty percent of patients developed > or = grade 2 thrombocytopenia. Grade 3 nausea and > or = grade 2 vomiting were observed in 40% and 47% of patients respectively. Thirty-three percent of patients experienced > or = grade 2 fatigue., Conclusions: MGI-114, at this dose and schedule, does not have significant activity as second line therapy for patients with advanced NSCLC.
- Published
- 2001
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38. Treatment outcome of lung cancer patients as optimized by preoperative whole-body positron emission tomography fluorodeoxyglucose imaging.
- Author
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Gupta NC, Bishop HA, Rogers JS, Tamim WZ, and Reesman SD
- Abstract
Positron emission tomography (PET) fluorodeoxyglucose (FDG) imaging may be more accurate than computed tomography (CT) scanning for staging of lung cancer disease. In the present study, we evaluate whether whole-body PET-FDG imaging can accurately stratify lung cancer patients by stage and thus predict patient outcome. Forty-one consecutive patients underwent whole-body PET and CT scanning for preoperative staging, which was then confirmed by mediastinoscopy, thoracotomy, and/or other tests revealing distant metastases. The effect of PET on patient management was determined. PET was significantly more accurate than CT for staging of lung cancer (97.6% vs. 70.7%). One-year follow-up for survival rate and treatment response was also compared in different patient groups. PET accurately identified patients with resectable disease (Group A). Group B patients, with medically inoperable disease, and Group C patients, with unresectable advanced disease, had 100% and 53% incidence of adverse events (defined as recurrence, evidence of new disease, or death), respectively. Group A patients with resectable disease who underwent surgery showed the best patient outcome, with only 7% incidence of adverse events. In conclusion, whole-body PET can be useful in identifying a group of lung cancer patients with resectable disease most likely to benefit from surgical resection. Further studies are needed to explore whether PET can predict patient outcome of various lung cancer patients receiving different treatment regimens.
- Published
- 2000
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39. Comparison of two systems for tibial external fixation in rabbits.
- Author
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Meffert RH, Tis JE, Lounici S, Rogers JS, Inoue N, and Chao EY
- Subjects
- Animals, Elasticity, Male, Osteogenesis, Distraction instrumentation, Rabbits, Stress, Mechanical, External Fixators, Fracture Fixation methods, Osteogenesis, Distraction methods, Tibia surgery
- Abstract
Background and Purpose: Use of rabbits in orthopedic investigations is common. In this study, focus is on factors that influence bone healing and on distraction osteogenesis. Biomechanical characteristics of two external fixator systems (Orthofix device and Hoffmann device) for long bones were tested., Methods: Twelve freshly dissected tibiae were obtained from six skeletally mature New Zealand White rabbits, and four-point bending stiffness in two planes (90 and 180 degrees to the fixator pins) and torsional stiffness and strength of the bone-fixator complex were evaluated by use of a material testing machine., Results: In four-point bending, Orthofix device had higher stiffness and strength, compared with Hoffmann device. When the load was applied 180 degrees to the pins, both devices had higher stiffness, compared with that at 90 degrees. In torsional testing, Orthofix device had significantly higher stiffness and strength., Conclusions: Significant differences in structural properties between the two systems were evident. Loading direction and gap conditions were important factors in determining properties of the systems. Therefore, type of external fixation system and fixation technique should be considered when designing experiments, using the rabbit long bone model.
- Published
- 1999
40. Multiple local maxima for likelihoods of phylogenetic trees: a simulation study.
- Author
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Rogers JS and Swofford DL
- Subjects
- Base Sequence, Classification methods, Likelihood Functions, Models, Molecular, Models, Statistical, Nucleotides classification, Phylogeny
- Abstract
Steel demonstrated that the maximum-likelihood function for a phylogenetic tree may have multiple local maxima. If this phenomenon were general, it would compromise the applicability of maximum likelihood as an optimality criterion for phylogenetic trees. In several simulation studies reported on in this paper, the true tree, and other trees of very high likelihood, rarely had multiple maxima. Our results thus provide reassurance that the value of maximum likelihood as a tree selection criterion is not compromised by the presence of multiple local maxima--the best estimates of the true tree are not likely to have them. This result holds true even when an incorrect nucleotide substitution model is used for tree selection.
- Published
- 1999
- Full Text
- View/download PDF
41. Comparative efficacy of positron emission tomography with FDG and computed tomographic scanning in preoperative staging of non-small cell lung cancer.
- Author
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Gupta NC, Graeber GM, Rogers JS 2nd, and Bishop HA
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Staging, Preoperative Care, Reproducibility of Results, Sensitivity and Specificity, Carcinoma, Non-Small-Cell Lung diagnosis, Carcinoma, Non-Small-Cell Lung secondary, Fluorodeoxyglucose F18, Lung Neoplasms diagnosis, Tomography, Emission-Computed, Tomography, X-Ray Computed
- Abstract
Objective: To determine the sensitivity, specificity, and accuracy of positron emission tomography with 2-fluorine-18-fluorodeoxyglucose (PET-FDG) in the preoperative staging (N and M staging) of patients with lung cancer. The authors wanted to compare the efficacy of PET scanning with currently used computed tomography (CT) scanning., Materials and Methods: Results of whole-body PET-FDG imaging and CT scans were compared with histologic findings for the presence or absence of lymph node disease or metastatic sites. Sampling of mediastinal lymph nodes was performed using mediastinoscopy or thoracotomy., Results: PET-FDG imaging was significantly more sensitive, specific, and accurate for detecting N disease than CT. PET changed N staging in 35% and M staging in 11% of patients. CT scans helped in accurate anatomic localization of 6/57 PET lymph node abnormalities., Conclusion: PET-FDG is a reliable method for preoperative staging of patients with lung cancer and would help to optimize management of these patients. Accurate lymph node staging of lung cancer may be ideally performed by simultaneous review of PET and CT scans.
- Published
- 1999
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42. A fast method for approximating maximum likelihoods of phylogenetic trees from nucleotide sequences.
- Author
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Rogers JS and Swofford DL
- Subjects
- Animals, Chordata, Nonvertebrate, DNA chemistry, DNA genetics, DNA, Ribosomal chemistry, DNA, Ribosomal genetics, Decision Trees, Likelihood Functions, RNA, Ribosomal genetics, Regression Analysis, Reproducibility of Results, Base Sequence, Phylogeny
- Abstract
We have developed a rapid parsimony method for reconstructing ancestral nucleotide states that allows calculation of initial branch lengths that are good approximations to optimal maximum-likelihood estimates under several commonly used substitution models. Use of these approximate branch lengths (rather than fixed arbitrary values) as starting points significantly reduces the time required for iteration to a solution that maximizes the likelihood of a tree. These branch lengths are close enough to the optimal values that they can be used without further iteration to calculate approximate maximum-likelihood scores that are very close to the "exact" scores found by iteration. Several strategies are described for using these approximate scores to substantially reduce times needed for maximum-likelihood tree searches.
- Published
- 1998
- Full Text
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43. Antiphospholipid antibodies: standardization and testing.
- Author
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Riley RS, Friedline J, and Rogers JS 2nd
- Subjects
- Antibodies, Antiphospholipid immunology, Female, Humans, Pregnancy, Quality Control, Terminology as Topic, Antibodies, Antiphospholipid analysis, Antiphospholipid Syndrome immunology, Blood Coagulation Tests standards
- Abstract
A phenomenon originally scorned as a laboratory nuisance has turned out to be an important cause of thromboembolism, fetal death, and other forms of human disease. Investigations of this inaptly named "lupus anticoagulant" has led to the discovery of at least two distinct types of autoimmune antibodies. In spite of recent discoveries regarding the pathophysiology of these antibodies, their clinical significance is still controversial.
- Published
- 1997
44. A cytoplasmic inhibitor of the JNK signal transduction pathway.
- Author
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Dickens M, Rogers JS, Cavanagh J, Raitano A, Xia Z, Halpern JR, Greenberg ME, Sawyers CL, and Davis RJ
- Subjects
- Activating Transcription Factor 2, Animals, COS Cells, Carrier Proteins chemistry, Cell Nucleus metabolism, Cell Transformation, Neoplastic, Cells, Cultured, Cloning, Molecular, Cyclic AMP Response Element-Binding Protein metabolism, Cytoplasm metabolism, Fusion Proteins, bcr-abl metabolism, Gene Expression Regulation, JNK Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 9, Molecular Sequence Data, Phosphorylation, Protein Kinases metabolism, Proto-Oncogene Proteins c-jun metabolism, Recombinant Fusion Proteins metabolism, Transcription Factors metabolism, Transcriptional Activation, Transfection, Calcium-Calmodulin-Dependent Protein Kinases metabolism, Carrier Proteins metabolism, Mitogen-Activated Protein Kinases, Signal Transduction
- Abstract
The c-Jun amino-terminal kinase (JNK) is a member of the stress-activated group of mitogen-activated protein (MAP) kinases that are implicated in the control of cell growth. A murine cytoplasmic protein that binds specifically to JNK [the JNK interacting protein-1 (JIP-1)] was characterized and cloned. JIP-1 caused cytoplasmic retention of JNK and inhibition of JNK-regulated gene expression. In addition, JIP-1 suppressed the effects of the JNK signaling pathway on cellular proliferation, including transformation by the Bcr-Abl oncogene. This analysis identifies JIP-1 as a specific inhibitor of the JNK signal transduction pathway and establishes protein targeting as a mechanism that regulates signaling by stress-activated MAP kinases.
- Published
- 1997
- Full Text
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45. The controversy of cranial bone motion.
- Author
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Rogers JS and Witt PL
- Subjects
- Animals, Cerebrospinal Fluid Pressure physiology, Humans, Intracranial Pressure physiology, Motion, Outcome Assessment, Health Care, Physical Therapy Modalities, Reproducibility of Results, Research, Sacrum physiology, Skull anatomy & histology, Chiropractic, Osteopathic Medicine, Skull physiology
- Abstract
Cranial bone motion continues to stimulate controversy. This controversy affects the general acceptance of some intervention methods used by physical therapists, namely, cranial osteopathic and craniosacral therapy techniques. Core to these intervention techniques is the belief that cranial bone mobility provides a compliant system where somatic dysfunction can occur and therapeutic techniques can be applied. Diversity of opinion over the truth of this concept characterizes differing viewpoints on the anatomy and physiology of the cranial complex. Literature on cranial bone motion was reviewed for the purpose of better understanding this topic. Published research overall was scant and inconclusive. Animal and human studies demonstrate a potential for small magnitude motion. Physical therapists should carefully scrutinize the literature presented as evidence for cranial bone motion. Further research is needed to resolve this controversy. Outcomes research, however, is needed to validate cranial bone mobilization as an effective treatment.
- Published
- 1997
- Full Text
- View/download PDF
46. On the consistency of maximum likelihood estimation of phylogenetic trees from nucleotide sequences.
- Author
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Rogers JS
- Subjects
- Base Sequence, Models, Genetic, Models, Statistical, Sequence Analysis statistics & numerical data, Likelihood Functions, Phylogeny
- Published
- 1997
- Full Text
- View/download PDF
47. Nitrate losses in runoff and subsurface drain effluent from controlled-water-table plots.
- Author
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Willis GH, Southwick LM, Fouss JL, Carter CE, and Rogers JS
- Subjects
- Rain, Fresh Water analysis, Nitrates analysis, Soil analysis
- Published
- 1997
- Full Text
- View/download PDF
48. Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine.
- Author
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Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ, and Davis RJ
- Subjects
- Animals, Calcium-Calmodulin-Dependent Protein Kinases analysis, Calcium-Calmodulin-Dependent Protein Kinases isolation & purification, Cell Line, Chlorocebus aethiops, Enzyme Activation, HeLa Cells, Humans, Inflammation, JNK Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 3, Molecular Weight, Osmolar Concentration, Phosphorylation, Phosphothreonine metabolism, Phosphotyrosine, Recombinant Proteins metabolism, Sequence Deletion, Stress, Physiological, Subcellular Fractions enzymology, Substrate Specificity, Transfection, Calcium-Calmodulin-Dependent Protein Kinases metabolism, Interleukin-1 pharmacology, Lipopolysaccharides pharmacology, Mitogen-Activated Protein Kinases, Threonine, Tumor Necrosis Factor-alpha pharmacology, Tyrosine analogs & derivatives, Tyrosine metabolism
- Abstract
Protein kinases activated by dual phosphorylation on Tyr and Thr (MAP kinases) can be grouped into two major classes: ERK and JNK. The ERK group regulates multiple targets in response to growth factors via a Ras-dependent mechanism. In contrast, JNK activates the transcription factor c-Jun in response to pro-inflammatory cytokines and exposure of cells to several forms of environmental stress. Recently, a novel mammalian protein kinase (p38) that shares sequence similarity with mitogen-activated protein (MAP) kinases was identified. Here, we demonstrate that p38, like JNK, is activated by treatment of cells with pro-inflammatory cytokines and environmental stress. The mechanism of p38 activation is mediated by dual phosphorylation on Thr-180 and Tyr-182. Immunofluorescence microscopy demonstrated that p38 MAP kinase is present in both the nucleus and cytoplasm of activated cells. Together, these data establish that p38 is a member of the mammalian MAP kinase group.
- Published
- 1995
- Full Text
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49. CENTRAL MOMENTS AND PROBABILITY DISTRIBUTION OF COLLESS'S COEFFICIENT OF TREE IMBALANCE.
- Author
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Rogers JS
- Abstract
The great increase in the number of phylogenetic studies of a wide variety of organisms in recent decades has focused considerable attention on the balance of phylogenetic trees-the degree to which sister clades within a tree tend to be of equal size-for at least two reasons: (1) the degree of balance of a tree may affect the accuracy of estimates of it; (2) the degree of balance, or imbalance, of a tree may reveal something about the macroevolutionary processes that produced it. In particular, variation among lineages in rates of speciation or extinction is expected to produce trees that are less balanced than those that result from phylogenetic evolution in which each extant species of a group has the same probability of speciation or extinction. Several coefficients for measuring the balance or imbalance of phylogenetic trees have been proposed. I focused on Colless's coefficient of imbalance (7) for its mathematical tractability and ease of interpretation. Earlier work on this statistic produced exact methods only for calculating the expected value. In those studies, the variance and confidence limits, which are necessary for testing the departure of observed values of I from the expected, were estimated by Monte Carlo simulation. I developed recursion equations that allow exact calculation of the mean, variance, skewness, and complete probability distribution of I for two different probability-generating models for bifurcating tree shapes. The Equal-Rates Markov (ERM) model assumes that trees grow by the random speciation and extinction of extant species, with all species that are extant at a given time having the same probability of speciation or extinction. The Equal Probability (EP) model assumes that all possible labeled trees for a given number of terminal taxa have the same probability of occurring. Examples illustrate how these theoretically derived probabilities and parameters may be used to test whether the evolution of a monophyletic group or set of monophyletic groups has proceeded according to a Markov model with equal rates of speciation and extinction among species, that is, whether there has been significant variation among lineages in expected rates of speciation or extinction., (© 1994 The Society for the Study of Evolution.)
- Published
- 1994
- Full Text
- View/download PDF
50. Inability to deflate the distal cuff of the laser-flex tracheal tube preventing extubation after laser surgery of the larynx.
- Author
-
Heyman DM, Greenfeld AL, Rogers JS, McCarthy BS, and Tucker J
- Subjects
- Humans, Male, Middle Aged, Equipment Failure, Intubation, Intratracheal instrumentation, Laryngeal Neoplasms surgery, Laser Therapy
- Published
- 1994
- Full Text
- View/download PDF
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