The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
Bryce Weir - One of the best experts on this subject based on the ideXlab platform.
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a review of hemoglobin and the pathogenesis of cerebral vasospasm
Stroke, 1991Co-Authors: R L Macdonald, Bryce WeirAbstract:We believe that current experimental and clinical evidence can be most satisfactorily interpreted by assuming that Oxyhemoglobin is the cause of cerebral vasospasm that follows subarachnoid hemorrhage. We review the pathogenetic mechanisms by which Oxyhemoglobin affects cerebral arteries. The relative importance of each of these mechanisms in the genesis of vasospasm, the biochemical pathways of Oxyhemoglobin-induced smooth muscle contraction, and the intracellular actions of Oxyhemoglobin on smooth muscle and on other cells in arteries are still not definitely established.
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free radicals mediate actions of Oxyhemoglobin on cerebrovascular smooth muscle cells
Circulation Research, 1991Co-Authors: J A Steele, N Stockbridge, G Maljkovic, Bryce WeirAbstract:Single smooth muscle cells were isolated from the basilar artery of the rat by enzymatic dispersion. The membrane properties of the cells were assessed using the patch-electrode voltage-clamp technique, and cell viability was monitored using fluorescein diacetate uptake. Exposure of the cells to Oxyhemoglobin (5 microM) resulted in 1) contraction, 2) the appearance of membrane blebs, 3) an increase in the outward potassium currents, 4) a decrease in the membrane resistance, and 5) cell death. In contrast, no effect of Oxyhemoglobin on cultured murine neuroblastoma cells was observed. Methemoglobin (100 microM) had no effects on the smooth muscle cells. Catalase (300 units/ml) or dimethyl sulfoxide (0.5%) protected against the effects of Oxyhemoglobin; superoxide dismutase (100-1,000 units/ml) provided only partial protection. Exposure of the cells to superoxide anions generated by xanthine (1 mM) plus xanthine oxidase (10 units/l) or to hydrogen peroxide (500 microM) caused an increase in the outward potassium currents without affecting membrane resistance. Generation of hydroxyl radicals by metal ions plus hydrogen peroxide caused the same effects as Oxyhemoglobin, that is, an increase in the potassium currents, followed by a decrease in the membrane resistance and cell death. In conclusion, it appears that Oxyhemoglobin exerts its effects on vascular smooth muscle cells by the generation of free radicals, chiefly hydroxyl radicals.
James A Dinardo - One of the best experts on this subject based on the ideXlab platform.
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measurement of dead space fraction upon icu admission predicts length of stay and clinical outcomes following bidirectional cavopulmonary anastomosis
Pediatric Critical Care Medicine, 2018Co-Authors: Claire L Cigarroa, Sarah J Van Den Bosch, Xiaoqi Tang, Kimberlee Gauvreau, Christopher W Baird, James A DinardoAbstract:OBJECTIVES Increased alveolar dead space fraction has been associated with prolonged mechanical ventilation and increased mortality in pediatric patients with respiratory failure. The association of alveolar dead space fraction with clinical outcomes in patients undergoing bidirectional cavopulmonary anastomosis for single ventricle congenital heart disease has not been reported. We describe an association of alveolar dead space fraction with postoperative outcomes in patients undergoing bidirectional cavopulmonary anastomosis. DESIGN In a retrospective case-control study, we examined for associations between alveolar dead space fraction ([PaCO2 - end-tidal CO2]/PaCO2), arterial Oxyhemoglobin saturation, and transpulmonary gradient upon postoperative ICU admission with a composite primary outcome (requirement for surgical or catheter-based intervention, death, or transplant prior to hospital discharge, defining cases) and several secondary endpoints in infants following bidirectional cavopulmonary anastomosis. SETTINGS Cardiac ICU in a tertiary care pediatric hospital. PATIENTS Patients undergoing bidirectional cavopulmonary anastomosis at our institution between 2011 and 2016. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Of 191 patients undergoing bidirectional cavopulmonary anastomosis, 28 patients were cases and 163 were controls. Alveolar dead space fraction was significantly higher in the case (0.26 ± 0.09) versus control group (0.17 ± 0.09; p < 0.001); alveolar dead space fraction at admission was less than 0.12 in 0% of cases and was greater than 0.28 in 35% of cases. Admission arterial Oxyhemoglobin saturation was significantly lower in the case (77% ± 12%) versus control group (83% ± 9%; p < 0.05). Sensitivity and specificity for future case versus control assignment was best when prebidirectional cavopulmonary anastomosis risk factors, admission alveolar dead space fraction (AUC, 0.74), and arterial Oxyhemoglobin saturation (AUC, 0.65) were combined in a summarial model (AUC, 0.83). For a given arterial Oxyhemoglobin saturation, the odds of becoming a case increased on average by 181% for every 0.1 unit increase in alveolar dead space fraction. Admission alveolar dead space fraction and arterial Oxyhemoglobin saturation were linearly associated with prolonged ICU length of stay, hospital length of stay, duration of mechanical ventilation, and duration of thoracic drainage (p < 0.001 for all). CONCLUSIONS Following bidirectional cavopulmonary anastomosis, alveolar dead space fraction in excess of 0.28 or arterial Oxyhemoglobin saturation less than 78% upon ICU admission indicates an increased likelihood of requiring intervention prior to hospital discharge. Increasing alveolar dead space fraction and decreasing arterial Oxyhemoglobin saturation are associated with increased lengths of stay.
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use of Oxyhemoglobin saturation rather than oxygen tension as a marker of oxygenation in cyanotic patients
JAMA Pediatrics, 2017Co-Authors: Xiaoqi Tang, Kimberlee Gauvreau, James A Dinardo, Humera Ahmed, Brian D Polizzotti, Mark D KelloggAbstract:This study analyzes clinically indicated arterial blood gas values from patients with cyanotic congenital heart disease to determine whether Oxyhemoglobin saturation or arterial oxygen tension provides a better measure of oxygenation.
E I Yuryeva - One of the best experts on this subject based on the ideXlab platform.
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chemical bonding and quadrupole splittings of 57fe mossbauer spectrum in active sites of Oxyhemoglobin as calculated by xα discrete variation method
Hyperfine Interactions, 2008Co-Authors: E I YuryevaAbstract:Results of quantum-chemical X α -discrete variation method (X α -DVM) calculations of interaction parameters between iron (II) and oxygen molecule in active sites of α- and β-subunits of Oxyhemoglobin are presented within three models: without extra electron and in spin-unrestricted mode (model I); without extra electron and in spin-restricted mode (model II); with extra electrons in spin-unrestricted mode (model III). The electronic structure and 57Fe quadrupole splitting ΔE Q for the active site of α- and β-subunits (within model I) and only of the α-subunit (within models II and III) of Oxyhemoglobin are calculated. The differences in ΔE Q values for these three models are discussed.
Darren Roblyer - One of the best experts on this subject based on the ideXlab platform.
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abstract 1408 diffuse optical spectroscopic imaging reveals regimen dependent changes in breast tumors throughout neoadjuvant chemotherapy
Cancer Research, 2019Co-Authors: Anup Tank, Hannah Peterson, Vivian Pera, Syeda Tabassum, Anais Leproux, Bruce J Tromberg, Darren RoblyerAbstract:Diffuse Optical Spectroscopic Imaging (DOSI) is a non-invasive near-infrared imaging modality than can provide label-free functional and metabolic information about breast tumors, probing depths up to several centimeters. Previous work has shown that DOSI has prognostic value for pathological response at key timepoints during neoadjuvant (presurgical) chemotherapy (NAC), including baseline, 24 hours after the first infusion, week 1, and at the midpoint of therapy. To date there have been almost no reports on how specific NAC regimens affect the prognostic capability of DOSI. Here we present a large multi-center DOSI dataset consisting of 54 breast tumors and 313 unique measurements taken across three timepoints during NAC: Baseline, week 1, and midpoint of treatment. We will show for the first time that the manifestation of DOSI response parameters (Oxyhemoglobin, de-Oxyhemoglobin, water, and lipid) is highly dependent on the specific NAC regimen used. Subjects were treated with either a Maximum Tolerated Dose (MTD) regimen, in which a higher dose is administered less frequently, or a Metronomic (MET) regimen, in which a smaller dose is given more frequently. MTD regimen of cytotoxic agents has traditionally been the most effective method to treat breast cancer as it aims to kill the maximum amount of tumor cells before regrowth. MET administration of cytotoxic therapies has shown antiangiogenic properties aiming to limit toxic side effects and drug resistance, while potentially inducing tumor dormancy and immunomodulation. Subjects treated with MTD regimen and also responding to this treatment exhibited an Oxyhemoglobin flare in the first day of NAC. In contrast, subjects treated with MET presented only small fluctuations in Oxyhemoglobin throughout the first week of NAC. The Oxyhemoglobin flare has been theorized to be induced by an inflammatory effect significant for cell death, which could be in response to specifically the MTD regimen and its higher dosing. This study indicates that the specific regimen must be considered when using DOSI for NAC monitoring. It also suggests DOSI may provide biological insight into the regimen-specific mechanisms of action. Citation Format: Anup Tank, Hannah Peterson, Vivian Pera, Syeda Tabassum, Naomi Ko, Anais Leproux, Bruce Tromberg, Darren Roblyer. Diffuse optical spectroscopic imaging reveals regimen-dependent changes in breast tumors throughout neoadjuvant chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1408.
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optical imaging of breast cancer Oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Darren Roblyer, Shigeto Ueda, Albert E Cerussi, Wendy Tanamai, Amanda Durkin, Rita S Mehta, David Hsiang, John Butler, Christine E Mclaren, Wenpin ChenAbstract:Approximately 8–20% of breast cancer patients receiving neoadjuvant chemotherapy fail to achieve a measurable response and endure toxic side effects without benefit. Most clinical and imaging measures of response are obtained several weeks after the start of therapy. Here, we report that functional hemodynamic and metabolic information acquired using a noninvasive optical imaging method on the first day after neoadjuvant chemotherapy treatment can discriminate nonresponding from responding patients. Diffuse optical spectroscopic imaging was used to measure absolute concentrations of Oxyhemoglobin, deOxyhemoglobin, water, and lipid in tumor and normal breast tissue of 24 tumors in 23 patients with untreated primary breast cancer. Measurements were made before chemotherapy, on day 1 after the first infusion, and frequently during the first week of therapy. Various multidrug, multicycle regimens were used to treat patients. Diffuse optical spectroscopic imaging measurements were compared with final postsurgical pathologic response. A statistically significant increase, or flare, in Oxyhemoglobin was observed in partial responding (n = 11) and pathologic complete responding tumors (n = 8) on day 1, whereas nonresponders (n = 5) showed no flare and a subsequent decrease in Oxyhemoglobin on day 1. Oxyhemoglobin flare on day 1 was adequate to discriminate nonresponding tumors from responding tumors. Very early measures of chemotherapy response are clinically convenient and offer the potential to alter treatment strategies, resulting in improved patient outcomes.
Naresh M. Punjabi - One of the best experts on this subject based on the ideXlab platform.
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impact of different hypopnea definitions on obstructive sleep apnea severity and cardiovascular mortality risk in women and elderly individuals
Sleep Medicine, 2016Co-Authors: Francisco Camposrodriguez, Miguel Angel Martinezgarcia, Nuria Reyesnunez, Maria Jose Selmaferrer, Ramon Farré, Naresh M. PunjabiAbstract:Abstract Objective To assess the impact of three hypopnea definitions on the severity classification of obstructive sleep apnea (OSA) and its association with cardiovascular mortality risk in women and elderly individuals. Methods We analyzed two Spanish clinical cohorts (1116 women and 939 elderly individuals) who were studied for suspicion of OSA between 1998 and 2007. A calibration model was used to apply different definitions of hypopnea to our two cohorts. Hypopnea was defined as a 30–90% reduction in oronasal flow for ≥10 s followed by (1) ≥4% fall in Oxyhemoglobin saturation—AHI 4% ; (2) ≥3% fall in Oxyhemoglobin saturation—AHI 3% ; or (3) ≥3% fall in Oxyhemoglobin saturation or an event-related arousal—AHI 3%a . Results In both cohorts, the prevalence of an AHI ≥30 events/h increased by 14% with AHI 3%a , compared to AHI 4% criteria. The percentage of women with an AHI 4% to 1.1% with the AHI 3%a definition. In fully adjusted multivariable analyses, AHI ≥30 events/h was associated with increased cardiovascular mortality risk in women, regardless of the hypopnea definition, and in elderly individuals diagnosed using the AHI 4% and AHI 3% but not the AHI 3%a definition. Conclusions Our findings suggest that hypopnea definitions substantially influence OSA prevalence and severity classification, and also affect the association with cardiovascular outcomes. With the currently recommended criterion (AHI 3%a ), a threshold of 30 events/h is appropriate to identify women, but not elderly individuals with increased risk of cardiovascular death.
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calibration model for apnea hypopnea indices impact of alternative criteria for hypopneas
Sleep, 2015Co-Authors: Vu Ho, Naresh M. Punjabi, Ciprian M. Crainiceanu, Susan Redline, Daniel J GottliebAbstract:STUDY OBJECTIVE: To characterize the association among apnea-hypopnea indices (AHIs) determined using three common metrics for defining hypopnea, and to develop a model to calibrate between these AHIs. DESIGN: Cross-sectional analysis of Sleep Heart Health Study Data. SETTING: Community-based. PARTICIPANTS: There were 6,441 men and women age 40 y or older. MEASUREMENT AND RESULTS: Three separate AHIs have been calculated, using all apneas (defined as a decrease in airflow greater than 90% from baseline for ≥ 10 sec) plus hypopneas (defined as a decrease in airflow or chest wall or abdominal excursion greater than 30% from baseline, but not meeting apnea definitions) associated with either: (1) a 4% or greater fall in Oxyhemoglobin saturation-AHI4; (2) a 3% or greater fall in Oxyhemoglobin saturation-AHI3; or (3) a 3% or greater fall in Oxyhemoglobin saturation or an event-related arousal-AHI3a. Median values were 5.4, 9.7, and 13.4 for AHI4, AHI3, and AHI3a, respectively (P < 0.0001). Penalized spline regression models were used to compare AHI values across the three metrics and to calculate prediction intervals. Comparison of regression models demonstrates divergence in AHI scores among the three methods at low AHI values and gradual convergence at higher levels of AHI. CONCLUSIONS: The three methods of scoring hypopneas yielded significantly different estimates of the apnea-hypopnea index (AHI), although the relative difference is reduced in severe disease. The regression models presented will enable clinicians and researchers to more appropriately compare AHI values obtained using differing metrics for hypopnea.
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fasting glycemia in sleep disordered breathing lowering the threshold on Oxyhemoglobin desaturation
Sleep, 2008Co-Authors: Katherine A Stamatakis, Daniel J Gottlieb, Reena Mehra, Mark H Sanders, Brian S Caffo, Helaine E Resnick, Naresh M. PunjabiAbstract:SLEEP DISORDERED BREATHING (SDB) IS A PREVALENT AND CHRONIC CONDITION THAT IS CHARACTERIZED BY RECURRENT EPISODES OF UPPER AIRWAY collapse during sleep. It is estimated that approximately 7% of adults in the general population have SDB of at least moderate severity.1 Several epidemiological and clinic-based studies have shown that the prevalence of altered glucose metabolism and type 2 diabetes increases with severity and frequency of self-reported and objective measures of SDB, independent of age and central obesity.2,3 Of the prospective observational studies, two have shown a higher incidence of type 2 diabetes mellitus among habitual snorers,4,5 and one has shown a higher prevalence of type 2 diabetes among those with polysomnographically defined SDB.6 Previous work from the Sleep Heart Health Study (SHHS) has also demonstrated a higher prevalence of impaired fasting glucose, glucose intolerance, and type 2 diabetes mellitus in individuals with SDB independent of body mass index and waist circumference.7 SDB is associated with a number of physiological derangements, including intermittent hypoxemia and sleep fragmentation. Experimental and observational studies that have attempted to uncouple these pathognomonic components of SDB have shown that both hypoxia and disrupted sleep can trigger a cascade of physiological events that may eventually result in altered glucose homeostasis. Increases in autonomic activity8,9 and circulating neuroendocrine hormones such as cortisol10,11 can be elicited by hypoxia and sleep disruption and thus may impair glucose metabolism in SDB. Epidemiologic observations from the SHHS cohort indicate that average Oxyhemoglobin saturation during sleep independently correlates with impaired glucose tolerance and type 2 diabetes.7 Thus, measures beside the conventional apnea-hypopnea index may provide a more nuanced understanding of the specific components of SDB that play a role in subsequent pathologies. In order to determine whether disordered breathing events with milder reductions in Oxyhemoglobin saturation that are excluded from conventional measures are clinically relevant, it is important to examine the full spectrum of SDB-related events in the context of specific health-related outcomes. The currently recommended criteria for defining a hypopnea include a reduction of airflow that is accompanied by an Oxyhemoglobin desaturation of at least 4%.12 An alternative definition includes a decrease in airflow with an Oxyhemoglobin desaturation of at least 3% or an arousal from sleep.12 Whether SDB events characterized by less stringent criteria for sleep related hypoxemia (e.g., 2% or 3% Oxyhemoglobin desaturation) are important for predicting the risk of adverse events is not known. To delineate the potential consequences of SDB events with lesser degrees of Oxyhemoglobin desaturation during sleep, the current study examined the association between events at varying thresholds of SDB-related oxygen desaturation and glucose metabolism. Specifically, the primary objective was to determine whether events, in particular hypopneas, based on an Oxyhemoglobin desaturation criterion below the 4% threshold for defining the disorder correlate with fasting glucose levels in a community-based sample of middle-aged and older adults.
