Robert Rodriguez - Academia.edu (original) (raw)
Papers by Robert Rodriguez
Western Journal of Emergency Medicine, 2021
Introduction: Considering the need for information regarding approaches to prevention and treatme... more Introduction: Considering the need for information regarding approaches to prevention and treatment of coronavirus disease 2019 (COVID-19), we sought to determine publication lag times of COVID-19-related original research articles published in top general medicine and emergency medicine (EM) journals. We further sought to characterize the types of COVID-19 publications within these journals. Methods: We reviewed 125 top-ranked general medicine journals and 20 top-ranked EM-specific journals for COVID-19-related publications. We abstracted article titles and manuscript details for each COVID-19-related article published between January 1–June 30, 2020, and categorized articles as one of the following: original research; case report; review; or commentary. We abstracted data for preprint publications over the same time period and determined whether articles from the general medicine and EM journals had been previously published as preprint articles. Our primary outcomes were the foll...
Academic Emergency Medicine, 2021
Comparing undocumented Latinx immigrants (UDLI), Latinx citizens/residents (LCR), and non‐Latinx ... more Comparing undocumented Latinx immigrants (UDLI), Latinx citizens/residents (LCR), and non‐Latinx citizens/residents (NLCR), we sought to assess rates of crime victimization, fear of reporting crimes, causes of this fear, and whether political rhetoric from the U.S. President had changed the reporting of crimes.
Journal of Sport Rehabilitation, 2019
Clinical Scenario: Ice hockey and soccer are both dynamic sports that involve continuous, unpredi... more Clinical Scenario: Ice hockey and soccer are both dynamic sports that involve continuous, unpredictable play. These athletes consistently demonstrate higher rates of groin strains compared with other contact sports. Measuring the hip adductor/abductor ratio has the potential to expose at-risk players, reduce injury rates, and preserve groin health in players with chronic strains. Focused Clinical Question: What is the clinical utility of measuring the hip adductor/abductor ratio for preseason and in-season ice hockey and soccer players? Summary of Key Findings: Three studies, all of which were prospective cohort designs, were included. One study involved assessing preseason strength and flexibility as a risk factor for adductor strains in professional ice hockey players. Another study performed with the same professional hockey team used preseason hip adductor/abductor strength ratios to screen for those players who would benefit from a strengthening intervention aimed at reducing t...
The Journal of emergency medicine, May 1, 2018
Tranexamic acid (TXA) is a synthetic anti-fibrinolytic agent used to prevent and treat various bl... more Tranexamic acid (TXA) is a synthetic anti-fibrinolytic agent used to prevent and treat various bleeding complications. In many studies, investigators have evaluated its utility and safety orally, intravenously, and topically, but few studies have described the potential benefits of nebulized TXA. We present a case of massive hemoptysis treated with nebulized TXA in the emergency department (ED) that led to the cessation of bleeding and avoidance of endotracheal intubation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In massive hemoptysis, rapidly available nebulized TXA may be considered a therapeutic option, serving either as primary therapy or as a bridge until other definitive therapies can be arranged.
PLOS Medicine, 2017
Validation of the sensitivity of the National Emergency X-Radiography Utilization Study (NEXUS) H... more Validation of the sensitivity of the National Emergency X-Radiography Utilization Study (NEXUS) Head computed tomographic (CT) decision instrument for selective imaging of blunt head injury patients: An observational study.
Http Dx Doi Org 10 3732 Apps 1200003, Jul 1, 2013
Biogeosciences Discussions, 2009
The effects of water limitations on the emission of biogenic volatile organic compounds are not w... more The effects of water limitations on the emission of biogenic volatile organic compounds are not well understood. Experimental approaches studying drought effects in natural conditions are still missing. To address this question, a throughfall displacement experiment was set up in a natural forest of Quercus ilex, an evergreen Mediterranean oak emitting monoterpenes. Mature trees were exposed in 2005 and 2006 either to an additional drought, to irrigation or to natural drought (untreated control). In both years, absolute monoterpene emission rates as well as the respective standard factors of the trees exposed to normal and additional drought strongly declined during the drought periods. Monoterpene emissions were lower in year 2006 than in year 2005 (factor 2) due to a more pronounced summer drought period in this respective year. We observed a significant difference between the irrigation and additional drought or control treatment: irrigated trees emitted 82% more monoterpenes during the drought period 2006 than the trees of the other treatments. However, no significant effect on monoterpene emission was observed between normal and additional drought treatments, despite a significant effect on leaf water potential and photochemical efficiency. During the development of drought, monoterpene emissions responded exponentially rather than linearly to decreasing leaf water potential. Emissions rapidly declined when the water potential dropped below −2 MPa and photosynthesis was persistently inhibited. Monoterpene synthase activities measured in vitro showed no clear reduction during the same period. From our results we conclude that drought significantly reduces monoterpene fluxes of Mediterranean evergreen forest into the atmosphere due to a sustained inhibition of photosynthetic carbon assimilation.
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, Jan 14, 2015
Major gaps persist in the development, validation, and implementation of clinical decision rules ... more Major gaps persist in the development, validation, and implementation of clinical decision rules (CDRs) for diagnostic imaging. The objective of this working group and article was to generate a consensus-based research agenda for the development and implementation of CDRs for diagnostic imaging in the emergency department (ED). The authors followed consensus methodology, as outlined by the journal Academic Emergency Medicine (AEM), combining literature review, electronic surveys, telephonic communications, and a modified nominal group technique. Final discussions occurred in person at the 2015 AEM consensus conference. A research agenda was developed, prioritizing the following questions: 1) what are the optimal methods to justify the derivation and validation of diagnostic imaging CDRs, 2) what level of evidence is required before disseminating CDRs for widespread implementation, 3) what defines a successful CDR, 4) how should investigators best compare CDRs to clinical judgment, a...
Cancer Research, 2015
Lung cancer is the leading cause of cancer-related death. The high prevalence coupled with the hi... more Lung cancer is the leading cause of cancer-related death. The high prevalence coupled with the high death rate and current lack of effective therapy against this type of cancer have spurred research on the characteristics of tumor cells and the search for novel strategies to prevent and treat lung cancer. The relationship between the degree of heterogeneity of tumor cells vs. the tumor cells sensitivity to anti-cancer agents may reflect the presence of cancer causing stem cells. The H460 non-small cell lung cancer cell line has been documented to have a great degree of heterogeneity with various degrees of responsiveness to the anti-cancer drug paclitaxel. The objective of this investigation was to assess the phenotypic heterogeneity of the H460 cell line following treatment with CPI-613. CPI-613 is a novel anti-cancer agent that selectively targets the altered form of mitochondrial energy metabolism utilized by tumor cells, that illicit changes in mitochondrial enzyme activities and cellular redox status leading to apoptosis, necrosis, and/or autophagia of tumor cells, without affecting normal cells. Different populations of H460 cells were generated following treatment of these cells with 1-2 rounds of CPI-613. The IC50 for the sub-population of H460 cells was approximately twice higher than that of parent H460 population (52±8 vs. 29±3 μM), suggesting the H460 cell line have CPI-613-sensitive and less sensitive sub-populations. Gene expression profiling revealed a difference in the metabolic and signaling pathways altered by CPI-613 among the different sub-populations. The cellular morphology observed under the microscope and up-regulation of SNAI2 and mesenchymal markers suggested that the sub-population consisted of cells with the epithelial-mesenchymal transition (EMT) phenotype. Recent evidence suggests that cells that undergo EMT gain stem cell-like properties, thus giving rise to cancer stem cells. We were able to demonstrate that treatment of parent H460 cells with CPI-613 at 50 μM for 24 hrs eliminated the sensitive population and treatment for 48 hrs was able to completely eliminate the resistant population containing cells with stem cell-like properties. Citation Format: Candida N. Perera, Robert Rodriguez, Robert Shorr. Heterogeneous response of H460 non-small lung carcinoma cells to CPI-613, a novel compound that selectively alters tumor energy metabolism. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A65. doi:10.1158/1538-7445.CHTME14-A65
Cancer Research, 2015
Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Pancreatic cance... more Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Pancreatic cancer is one of the most devastating human malignancies with an estimate yearly death of 280,000 and an overall median 5-year survival rate of less than 5%. The development of relevant preclinical models of the disease to evaluate novel therapeutic strategies can accelerate basic research findings into the much needed clinical application. We used our recently established three-dimensional (3D) in vitro culture assay system that resembles in-vivo tumor growth to screen small molecule libraries. We identified CEP1430, a sonic hedgehog (hh) pathway inhibitor as a potential drug lead molecule. We selected this molecule for further evaluation because the hh pathway is important for the maintenance of cancer stem cells. The CEP1430 treatment markedly inhibited in-vitro growth of human pancreatic CSC (IC50 value of ∼10 nM). In-vitro, CEP1430 induced apoptotic cell death of CSC and reduced pro-angiogenic but increased anti-angiogenic marker expression at the doses tested. In-vivo efficacy of CEP 1430 was evaluated in female SCID mice bearing human pancreatic CSC. The once daily administration (ip) of CEP1430 (doses:10, 15, and 20 mg/kg) for 30 days resulted in 80%, 89% and 90% tumor growth inhibition. The tumor growth inhibitory effect of CEP1430 in all treatment groups was statistically significant in comparison to vehicle treated control (P<0.001). The administration of CEP1430 for a period of 30 days was well tolerated without significant changes in body weight or toxicity by histological examination of tissues and organs. We are using proteomic and miRNA platforms to monitor biomarkers of response, mode of action and selectivity of CEP1430. Further pre-clinical in-vivo studies are ongoing to project human dose and schedule as monotherapy and in combination with therapeutic vaccination to advance CEP1430 for clinical investigation. Citation Format: Jitesh Jani, Mandana Amiri, Cristian Sharma, Joshua Harris, Shruthi Satish, Michael Sharma, Robert Rodriguez, Miriam Navel, Natalee Amezcua, Shaleekha Sharma, Arun Sharma, Dhimant Desai, Shantu Amin, Satya Narayan, Rubio Punzalan, Jay P. Sharma. A novel pharmacological inhibitor CEP1430 for human pancreatic cancer stem cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4225. doi:10.1158/1538-7445.AM2015-4225
The Journal of emergency medicine, Jan 21, 2015
Although x-ray studies provide important diagnostic information during trauma resuscitations, the... more Although x-ray studies provide important diagnostic information during trauma resuscitations, they may also lead to significant interruptions in care. We sought to determine the frequency and duration of interruptions for chest x-ray studies (CXR) and pelvic x-ray studies (PXR) and the frequency of lead apron use among providers who exited trauma rooms during resuscitation. Using a convenience sampling method, we conducted a prospective, observational study from August 2013 to March 2014, enrolling adult trauma patients at a Level I trauma center who received CXR and PXR in the first 30 min of evaluation. An observer stood outside resuscitation rooms and recorded the time elapsed from the first provider exiting the room to the last provider returning. We recorded how many exiting providers wore lead aprons and whether unused aprons were available. Of the 156 trauma cases observed, 67.3% were of male patients with a mean age of 52 years (interquartile range [IQR] 34-67 years); 97.4% ...
Medicina clínica, Jan 13, 1998
Endogenously synthesized nitric oxide (NO) is present in exhaled air and its analysis could be us... more Endogenously synthesized nitric oxide (NO) is present in exhaled air and its analysis could be used as a tool to monitor inflammatory airway diseases. The objective of the present study was to develop the methodology for the measurement of exhaled NO and to obtain reference values in a group of healthy subjects. Exhaled NO was measured in 40 healthy subjects and 22 asthmatic patients using a single breath manoeuvre and a chemiluminescence analyzer. Comparisons of exhaled NO while breathing both, room air and medical air, were performed in 20 subjects. In seven asthmatic patients we evaluated the effect of an inhibitor of NO-synthesis (L-NAME). Mean (SD) exhaled NO in healthy subjects was 18 (13) parts per billion (ppb). Intraindividual variability was 6.5 (6.5%). The concentration of exhaled NO could be overestimated when environmental NO was high (> 80 ppb). Smokers showed lower levels than nonsmokers (10 [7] vs 22 [13] ppb, respectively; p < 0.005), whereas asthmatic patient...
The European respiratory journal, 1993
Medicina clínica, Jan 15, 1983
Medicina clínica, Jan 12, 1985
New England Journal of Medicine, 2014
Background Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators... more Background Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long-acting bronchodilators has not been fully explored. Methods In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric findings, health status, and dyspnea were also monitored. Results As compared with continued glucocorticoid use, glucocorticoid withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval (CI) with respect to the first moderate or severe COPD exacerbation (hazard ratio, 1.06; 95% CI, 0.94 to 1.19). At week 18, when glucocorticoid withdrawal was complete, the adjusted mean reduction from baseline in the trough forced expiratory volume in 1 second was 38 ml greater in the glucocorticoid-withdrawal group than in the glucocorticoid-continuation group (P<0.001); a similar between-group difference (43 ml) was seen at week 52 (P = 0.001). No change in dyspnea and minor changes in health status occurred in the glucocorticoid-withdrawal group. Conclusions In patients with severe COPD receiving tiotropium plus salmeterol, the risk of moderate or severe exacerbations was similar among those who discontinued inhaled glucocorticoids and those who continued glucocorticoid therapy. However, there was a greater decrease in lung function during the final step of glucocorticoid withdrawal. (Funded by Boehringer Ingelheim Pharma; WISDOM ClinicalTrials.gov number, NCT00975195.
American Review of Respiratory Disease, 1993
We have investigated the time course of ventilation-perfusion (VA/Q) mismatch and airflow obstruc... more We have investigated the time course of ventilation-perfusion (VA/Q) mismatch and airflow obstruction in 18 patients with acute severe asthma with the objective to identify potential differences according to the clinical severity of the attacks. Nine patients were hospitalized and nine were discharged (emergency room stay < 24 h) according to the clinical criteria of the attending physicians. Spirometry and VA/Q inequality (multiple inert gas technique) were measured within the first 6 h of treatment in the emergency room, and at Weeks 1,2,3, and 4 thereafter. In the emergency room [corrected] hospitalized patients (in relation to those discharged) showed lower airflow rates (FEV1, 31 +/- 3 versus 46 +/- 6% predicted SEM) and greater VA/Q mismatch (as assessed by the dispersion of blood flow distributions (logSD Q) (1.28 +/- 0.11 versus 0.92 +/- 0.11; normal values < 0.6). Even though the rate of improvement of airflow was similar in both groups (without returning to normal limits), VA/Q relationships improved at different rates in each group and reached normal values at the end of the study. Although in hospitalized patients the recovery of VA/Q abnormalities was delayed in relation to airflow rates, the time course in discharged patients was the same. Previous studies have shown a dissociation between spirometry and VA/Q inequality, suggesting that whereas airflow rates predominantly reflect bronchoconstriction of large airways, VA/Q mismatch is more related to obstructive changes in peripheral airways. Our results support this hypothesis and suggest that the more severe the asthma attacks, the more severe the obstructive changes involving peripheral airways for a given degree of widespread airway narrowing.
Asthma Treatment, 1992
... Lancet, 1:644 (1967). 2. McFadden ER, Lyons HA. ... asthma. Am Rev Respir Dis 118:304 (1978).... more ... Lancet, 1:644 (1967). 2. McFadden ER, Lyons HA. ... asthma. Am Rev Respir Dis 118:304 (1978). 5. Ballester E, Reyes A, Roca J, Guitart R, Wagner PO, Rodriguez-Roisin R. Ventilation-perfusion mismatching in acute severe asthma: effects of salbutamol and 100% oxygen. ...
Western Journal of Emergency Medicine, 2021
Introduction: Considering the need for information regarding approaches to prevention and treatme... more Introduction: Considering the need for information regarding approaches to prevention and treatment of coronavirus disease 2019 (COVID-19), we sought to determine publication lag times of COVID-19-related original research articles published in top general medicine and emergency medicine (EM) journals. We further sought to characterize the types of COVID-19 publications within these journals. Methods: We reviewed 125 top-ranked general medicine journals and 20 top-ranked EM-specific journals for COVID-19-related publications. We abstracted article titles and manuscript details for each COVID-19-related article published between January 1–June 30, 2020, and categorized articles as one of the following: original research; case report; review; or commentary. We abstracted data for preprint publications over the same time period and determined whether articles from the general medicine and EM journals had been previously published as preprint articles. Our primary outcomes were the foll...
Academic Emergency Medicine, 2021
Comparing undocumented Latinx immigrants (UDLI), Latinx citizens/residents (LCR), and non‐Latinx ... more Comparing undocumented Latinx immigrants (UDLI), Latinx citizens/residents (LCR), and non‐Latinx citizens/residents (NLCR), we sought to assess rates of crime victimization, fear of reporting crimes, causes of this fear, and whether political rhetoric from the U.S. President had changed the reporting of crimes.
Journal of Sport Rehabilitation, 2019
Clinical Scenario: Ice hockey and soccer are both dynamic sports that involve continuous, unpredi... more Clinical Scenario: Ice hockey and soccer are both dynamic sports that involve continuous, unpredictable play. These athletes consistently demonstrate higher rates of groin strains compared with other contact sports. Measuring the hip adductor/abductor ratio has the potential to expose at-risk players, reduce injury rates, and preserve groin health in players with chronic strains. Focused Clinical Question: What is the clinical utility of measuring the hip adductor/abductor ratio for preseason and in-season ice hockey and soccer players? Summary of Key Findings: Three studies, all of which were prospective cohort designs, were included. One study involved assessing preseason strength and flexibility as a risk factor for adductor strains in professional ice hockey players. Another study performed with the same professional hockey team used preseason hip adductor/abductor strength ratios to screen for those players who would benefit from a strengthening intervention aimed at reducing t...
The Journal of emergency medicine, May 1, 2018
Tranexamic acid (TXA) is a synthetic anti-fibrinolytic agent used to prevent and treat various bl... more Tranexamic acid (TXA) is a synthetic anti-fibrinolytic agent used to prevent and treat various bleeding complications. In many studies, investigators have evaluated its utility and safety orally, intravenously, and topically, but few studies have described the potential benefits of nebulized TXA. We present a case of massive hemoptysis treated with nebulized TXA in the emergency department (ED) that led to the cessation of bleeding and avoidance of endotracheal intubation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In massive hemoptysis, rapidly available nebulized TXA may be considered a therapeutic option, serving either as primary therapy or as a bridge until other definitive therapies can be arranged.
PLOS Medicine, 2017
Validation of the sensitivity of the National Emergency X-Radiography Utilization Study (NEXUS) H... more Validation of the sensitivity of the National Emergency X-Radiography Utilization Study (NEXUS) Head computed tomographic (CT) decision instrument for selective imaging of blunt head injury patients: An observational study.
Http Dx Doi Org 10 3732 Apps 1200003, Jul 1, 2013
Biogeosciences Discussions, 2009
The effects of water limitations on the emission of biogenic volatile organic compounds are not w... more The effects of water limitations on the emission of biogenic volatile organic compounds are not well understood. Experimental approaches studying drought effects in natural conditions are still missing. To address this question, a throughfall displacement experiment was set up in a natural forest of Quercus ilex, an evergreen Mediterranean oak emitting monoterpenes. Mature trees were exposed in 2005 and 2006 either to an additional drought, to irrigation or to natural drought (untreated control). In both years, absolute monoterpene emission rates as well as the respective standard factors of the trees exposed to normal and additional drought strongly declined during the drought periods. Monoterpene emissions were lower in year 2006 than in year 2005 (factor 2) due to a more pronounced summer drought period in this respective year. We observed a significant difference between the irrigation and additional drought or control treatment: irrigated trees emitted 82% more monoterpenes during the drought period 2006 than the trees of the other treatments. However, no significant effect on monoterpene emission was observed between normal and additional drought treatments, despite a significant effect on leaf water potential and photochemical efficiency. During the development of drought, monoterpene emissions responded exponentially rather than linearly to decreasing leaf water potential. Emissions rapidly declined when the water potential dropped below −2 MPa and photosynthesis was persistently inhibited. Monoterpene synthase activities measured in vitro showed no clear reduction during the same period. From our results we conclude that drought significantly reduces monoterpene fluxes of Mediterranean evergreen forest into the atmosphere due to a sustained inhibition of photosynthetic carbon assimilation.
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, Jan 14, 2015
Major gaps persist in the development, validation, and implementation of clinical decision rules ... more Major gaps persist in the development, validation, and implementation of clinical decision rules (CDRs) for diagnostic imaging. The objective of this working group and article was to generate a consensus-based research agenda for the development and implementation of CDRs for diagnostic imaging in the emergency department (ED). The authors followed consensus methodology, as outlined by the journal Academic Emergency Medicine (AEM), combining literature review, electronic surveys, telephonic communications, and a modified nominal group technique. Final discussions occurred in person at the 2015 AEM consensus conference. A research agenda was developed, prioritizing the following questions: 1) what are the optimal methods to justify the derivation and validation of diagnostic imaging CDRs, 2) what level of evidence is required before disseminating CDRs for widespread implementation, 3) what defines a successful CDR, 4) how should investigators best compare CDRs to clinical judgment, a...
Cancer Research, 2015
Lung cancer is the leading cause of cancer-related death. The high prevalence coupled with the hi... more Lung cancer is the leading cause of cancer-related death. The high prevalence coupled with the high death rate and current lack of effective therapy against this type of cancer have spurred research on the characteristics of tumor cells and the search for novel strategies to prevent and treat lung cancer. The relationship between the degree of heterogeneity of tumor cells vs. the tumor cells sensitivity to anti-cancer agents may reflect the presence of cancer causing stem cells. The H460 non-small cell lung cancer cell line has been documented to have a great degree of heterogeneity with various degrees of responsiveness to the anti-cancer drug paclitaxel. The objective of this investigation was to assess the phenotypic heterogeneity of the H460 cell line following treatment with CPI-613. CPI-613 is a novel anti-cancer agent that selectively targets the altered form of mitochondrial energy metabolism utilized by tumor cells, that illicit changes in mitochondrial enzyme activities and cellular redox status leading to apoptosis, necrosis, and/or autophagia of tumor cells, without affecting normal cells. Different populations of H460 cells were generated following treatment of these cells with 1-2 rounds of CPI-613. The IC50 for the sub-population of H460 cells was approximately twice higher than that of parent H460 population (52±8 vs. 29±3 μM), suggesting the H460 cell line have CPI-613-sensitive and less sensitive sub-populations. Gene expression profiling revealed a difference in the metabolic and signaling pathways altered by CPI-613 among the different sub-populations. The cellular morphology observed under the microscope and up-regulation of SNAI2 and mesenchymal markers suggested that the sub-population consisted of cells with the epithelial-mesenchymal transition (EMT) phenotype. Recent evidence suggests that cells that undergo EMT gain stem cell-like properties, thus giving rise to cancer stem cells. We were able to demonstrate that treatment of parent H460 cells with CPI-613 at 50 μM for 24 hrs eliminated the sensitive population and treatment for 48 hrs was able to completely eliminate the resistant population containing cells with stem cell-like properties. Citation Format: Candida N. Perera, Robert Rodriguez, Robert Shorr. Heterogeneous response of H460 non-small lung carcinoma cells to CPI-613, a novel compound that selectively alters tumor energy metabolism. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A65. doi:10.1158/1538-7445.CHTME14-A65
Cancer Research, 2015
Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Pancreatic cance... more Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Pancreatic cancer is one of the most devastating human malignancies with an estimate yearly death of 280,000 and an overall median 5-year survival rate of less than 5%. The development of relevant preclinical models of the disease to evaluate novel therapeutic strategies can accelerate basic research findings into the much needed clinical application. We used our recently established three-dimensional (3D) in vitro culture assay system that resembles in-vivo tumor growth to screen small molecule libraries. We identified CEP1430, a sonic hedgehog (hh) pathway inhibitor as a potential drug lead molecule. We selected this molecule for further evaluation because the hh pathway is important for the maintenance of cancer stem cells. The CEP1430 treatment markedly inhibited in-vitro growth of human pancreatic CSC (IC50 value of ∼10 nM). In-vitro, CEP1430 induced apoptotic cell death of CSC and reduced pro-angiogenic but increased anti-angiogenic marker expression at the doses tested. In-vivo efficacy of CEP 1430 was evaluated in female SCID mice bearing human pancreatic CSC. The once daily administration (ip) of CEP1430 (doses:10, 15, and 20 mg/kg) for 30 days resulted in 80%, 89% and 90% tumor growth inhibition. The tumor growth inhibitory effect of CEP1430 in all treatment groups was statistically significant in comparison to vehicle treated control (P<0.001). The administration of CEP1430 for a period of 30 days was well tolerated without significant changes in body weight or toxicity by histological examination of tissues and organs. We are using proteomic and miRNA platforms to monitor biomarkers of response, mode of action and selectivity of CEP1430. Further pre-clinical in-vivo studies are ongoing to project human dose and schedule as monotherapy and in combination with therapeutic vaccination to advance CEP1430 for clinical investigation. Citation Format: Jitesh Jani, Mandana Amiri, Cristian Sharma, Joshua Harris, Shruthi Satish, Michael Sharma, Robert Rodriguez, Miriam Navel, Natalee Amezcua, Shaleekha Sharma, Arun Sharma, Dhimant Desai, Shantu Amin, Satya Narayan, Rubio Punzalan, Jay P. Sharma. A novel pharmacological inhibitor CEP1430 for human pancreatic cancer stem cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4225. doi:10.1158/1538-7445.AM2015-4225
The Journal of emergency medicine, Jan 21, 2015
Although x-ray studies provide important diagnostic information during trauma resuscitations, the... more Although x-ray studies provide important diagnostic information during trauma resuscitations, they may also lead to significant interruptions in care. We sought to determine the frequency and duration of interruptions for chest x-ray studies (CXR) and pelvic x-ray studies (PXR) and the frequency of lead apron use among providers who exited trauma rooms during resuscitation. Using a convenience sampling method, we conducted a prospective, observational study from August 2013 to March 2014, enrolling adult trauma patients at a Level I trauma center who received CXR and PXR in the first 30 min of evaluation. An observer stood outside resuscitation rooms and recorded the time elapsed from the first provider exiting the room to the last provider returning. We recorded how many exiting providers wore lead aprons and whether unused aprons were available. Of the 156 trauma cases observed, 67.3% were of male patients with a mean age of 52 years (interquartile range [IQR] 34-67 years); 97.4% ...
Medicina clínica, Jan 13, 1998
Endogenously synthesized nitric oxide (NO) is present in exhaled air and its analysis could be us... more Endogenously synthesized nitric oxide (NO) is present in exhaled air and its analysis could be used as a tool to monitor inflammatory airway diseases. The objective of the present study was to develop the methodology for the measurement of exhaled NO and to obtain reference values in a group of healthy subjects. Exhaled NO was measured in 40 healthy subjects and 22 asthmatic patients using a single breath manoeuvre and a chemiluminescence analyzer. Comparisons of exhaled NO while breathing both, room air and medical air, were performed in 20 subjects. In seven asthmatic patients we evaluated the effect of an inhibitor of NO-synthesis (L-NAME). Mean (SD) exhaled NO in healthy subjects was 18 (13) parts per billion (ppb). Intraindividual variability was 6.5 (6.5%). The concentration of exhaled NO could be overestimated when environmental NO was high (> 80 ppb). Smokers showed lower levels than nonsmokers (10 [7] vs 22 [13] ppb, respectively; p < 0.005), whereas asthmatic patient...
The European respiratory journal, 1993
Medicina clínica, Jan 15, 1983
Medicina clínica, Jan 12, 1985
New England Journal of Medicine, 2014
Background Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators... more Background Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long-acting bronchodilators has not been fully explored. Methods In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric findings, health status, and dyspnea were also monitored. Results As compared with continued glucocorticoid use, glucocorticoid withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval (CI) with respect to the first moderate or severe COPD exacerbation (hazard ratio, 1.06; 95% CI, 0.94 to 1.19). At week 18, when glucocorticoid withdrawal was complete, the adjusted mean reduction from baseline in the trough forced expiratory volume in 1 second was 38 ml greater in the glucocorticoid-withdrawal group than in the glucocorticoid-continuation group (P<0.001); a similar between-group difference (43 ml) was seen at week 52 (P = 0.001). No change in dyspnea and minor changes in health status occurred in the glucocorticoid-withdrawal group. Conclusions In patients with severe COPD receiving tiotropium plus salmeterol, the risk of moderate or severe exacerbations was similar among those who discontinued inhaled glucocorticoids and those who continued glucocorticoid therapy. However, there was a greater decrease in lung function during the final step of glucocorticoid withdrawal. (Funded by Boehringer Ingelheim Pharma; WISDOM ClinicalTrials.gov number, NCT00975195.
American Review of Respiratory Disease, 1993
We have investigated the time course of ventilation-perfusion (VA/Q) mismatch and airflow obstruc... more We have investigated the time course of ventilation-perfusion (VA/Q) mismatch and airflow obstruction in 18 patients with acute severe asthma with the objective to identify potential differences according to the clinical severity of the attacks. Nine patients were hospitalized and nine were discharged (emergency room stay < 24 h) according to the clinical criteria of the attending physicians. Spirometry and VA/Q inequality (multiple inert gas technique) were measured within the first 6 h of treatment in the emergency room, and at Weeks 1,2,3, and 4 thereafter. In the emergency room [corrected] hospitalized patients (in relation to those discharged) showed lower airflow rates (FEV1, 31 +/- 3 versus 46 +/- 6% predicted SEM) and greater VA/Q mismatch (as assessed by the dispersion of blood flow distributions (logSD Q) (1.28 +/- 0.11 versus 0.92 +/- 0.11; normal values < 0.6). Even though the rate of improvement of airflow was similar in both groups (without returning to normal limits), VA/Q relationships improved at different rates in each group and reached normal values at the end of the study. Although in hospitalized patients the recovery of VA/Q abnormalities was delayed in relation to airflow rates, the time course in discharged patients was the same. Previous studies have shown a dissociation between spirometry and VA/Q inequality, suggesting that whereas airflow rates predominantly reflect bronchoconstriction of large airways, VA/Q mismatch is more related to obstructive changes in peripheral airways. Our results support this hypothesis and suggest that the more severe the asthma attacks, the more severe the obstructive changes involving peripheral airways for a given degree of widespread airway narrowing.
Asthma Treatment, 1992
... Lancet, 1:644 (1967). 2. McFadden ER, Lyons HA. ... asthma. Am Rev Respir Dis 118:304 (1978).... more ... Lancet, 1:644 (1967). 2. McFadden ER, Lyons HA. ... asthma. Am Rev Respir Dis 118:304 (1978). 5. Ballester E, Reyes A, Roca J, Guitart R, Wagner PO, Rodriguez-Roisin R. Ventilation-perfusion mismatching in acute severe asthma: effects of salbutamol and 100% oxygen. ...