15 results on '"Meduri, C."'
Search Results
2. Effect of temperature on shear bands and bending plasticity of metallic glasses
- Author
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Meduri, C., Hasan, M., Adam, S., and Kumar, G.
- Published
- 2018
- Full Text
- View/download PDF
3. Imaging for Tricuspid Valve Repair and Replacement
- Author
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Agricola, E, Asmarats, L, Maisano, F, Cavalcante, JL, Liu, SZ, Milla, F, Meduri, C, Rodes-Cabau, J, Vannan, M, and Pibarot, P
- Subjects
transesophageal echocardiography ,cinefluoroscopy ,computed tomography ,tricuspid valve ,transcatheter valve therapy ,fusion imaging ,tricuspid regurgitation ,Doppler echocardiography ,tricuspid valve intervention - Abstract
Primary or secondary tricuspid regurgitation (TR) represents an important health care burden and challenge which has often been neglected or undertreated in the past. The expansion and reinforcement of the indications for tricuspid valve (TV) intervention in the 2017 editions of the guidelines as well as the introduction of transcatheter tricuspid valve intervention (TTVI) has considerably increased the attention of the community on the TV and the volume of TV interventions in the past years. Depending on the anatomic target, TTVI can be categorized as the following: 1) direct or indirect tricuspid restrictive annuloplasty; 2) direct (edge-to-edge repair) or indirect (coaptation device) restoration of leaflet coaptation; 3) heterotopic tricuspid valve implantation; and 4) transcatheter tricuspid valve replacement. Multi-modality imaging has crucial role for the following: 1) patient selection for TTVI and procedure planning; 2) guiding and monitoring the procedure; and 3) assessing and following over time the results of the procedure. The key points for pre-procedural imaging are: 1) accurate quantitation of TR severity; 2) proper identification of the mechanism(s) responsible for the TR; and 3) quantitation of RV dysfunction and pulmonary arterial hypertension. This imaging work-up is essential to select the right type of intervention for the right patient and TV. Transesophageal echocardiography and fluoroscopy imaging is also key for guiding the TTVI procedures and fusion between these 2 modalities may further enhance the quality of procedure guiding. (C) 2021 by the American College of Cardiology Foundation.
- Published
- 2021
4. Comorbidity status of deceased COVID-19 in-patients in Italy
- Author
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Vetrano, D. L., Tazzeo, C., Palmieri, L., Marengoni, A., Zucchelli, A., Lo Noce, C., Onder, G., Andrianou, X., Barbariol, P., Bella, A., Bellino, S., Benelli, E., Bertinato, L., Boros, S., Brambilla, G., Calcagnini, G., Canevelli, M., Castrucci, M. R., Censi, F., Ciervo, A., Colaizzo, E., D'Ancona, F., Del Manso, M., Di Benedetto, C., Donfrancesco, C., Fabiani, M., Facchiano, F., Filia, A., Floridia, M., Galati, F., Giuliano, M., Grisetti, T., Kodra, Y., Langer, M., Lega, I., Maiozzi, P., Malchiodi Albedi, F., Manno, V., Martini, M., Urdiales, A. M., Mattei, E., Meduri, C., Meli, P., Minelli, G., Nebuloni, M., Nistico, L., Nonis, M., Palmisano, L., Petrosillo, N., Pezzotti, P., Pricci, F., Punzo, O., Puro, V., Raparelli, V., Rezza, G., Riccardo, F., Rota, M. C., Salerno, P., Serra, D., Siddu, A., Stefanelli, P., Tamburo de Bella, M., Tiple, D., Unim, B., Vaianella, L., Vanacore, N., Vichi, M., Villani, E. R., Zona, A., and Brusaferro, S.
- Subjects
Aging ,medicine.medical_specialty ,Short Communication ,Disease ,Type 2 diabetes ,Comorbidity ,Chronic disease ,NO ,03 medical and health sciences ,0302 clinical medicine ,COVID-19 ,Mortality ,Multimorbidity ,Risk Factors ,Internal medicine ,medicine ,80 and over ,Diabetes Mellitus ,Dementia ,Humans ,030212 general & internal medicine ,Stroke ,Aged ,Aged, 80 and over ,COPD ,business.industry ,SARS-CoV-2 ,Atrial fibrillation ,Italy ,Diabetes Mellitus, Type 2 ,medicine.disease ,030228 respiratory system ,Heart failure ,Geriatrics and Gerontology ,business ,Type 2 - Abstract
Background Most COVID-19-related deaths have occurred in older persons with comorbidities. Specific patterns of comorbidities related to COVID-19 deaths have not been investigated. Methods A random sample of 6085 individuals in Italy who died in-hospital with confirmed COVID-19 between February and December 2020 were included. Observed to expected (O/E) ratios of disease pairs were computed and logistic regression models were used to determine the association between disease pairs with O/E values ≥ 1.5. Results Six pairs of diseases exhibited O/E values ≥ 1.5 and statistically significant higher odds of co-occurrence in the crude and adjusted analyses: (1) ischemic heart disease and atrial fibrillation, (2) atrial fibrillation and heart failure, (3) atrial fibrillation and stroke, (4) heart failure and COPD, (5) stroke and dementia, and (6) type 2 diabetes and obesity. Conclusion In those deceased in-hospital due to COVID-19 in Italy, disease combinations defined by multiple cardio-respiratory, metabolic, and neuropsychiatric diseases occur more frequently than expected. This finding indicates a need to investigate the possible role of these clinical profiles in the chain of events that lead to death in individuals who have contracted SARS-CoV-2.
- Published
- 2021
5. The CUORE project cardiovascular risk assessment in primary care: the ongoing experience in Italy
- Author
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Palmieri, L, primary, Vannucchi, S, additional, Lo Noce, C, additional, Di Lonardo, A, additional, Unim, B, additional, Grisetti, T, additional, Meduri, C, additional, and Donfrancesco, C, additional
- Published
- 2020
- Full Text
- View/download PDF
6. Sex differences in clinical phenotype and transitions of care among individuals dying of COVID-19 in Italy
- Author
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Raparelli, V., Palmieri, L., Canevelli, M., Pricci, F., Unim, B., Lo Noce, C., Villani, E. R., Rochon, P. A., Pilote, L., Vanacore, N., Onder, G., Agazio, E., Andrianou, X., Barbariol, P., Bella, A., Bellino, S., Benelli, E., Bertinato, L., Boros, S., Brambilla, G., Calcagnini, G., Daqar, Q. Z., Castrucci, M. R., Censi, F., Ciervo, A., Colaizzo, E., D'Ancona, F., Delmanso, M., Donfrancesco, C., Fabiani, M., Facchiano, F., Filia, A., Floridia, M., Galati, F., Giuliano, M., Grisetti, T., Kodra, Y., Langer, M., Lega, I., Lonoce, C., Maiozzi, P., Malchiodialbedi, F., Manno, V., Martini, M., Urdiales, A. M., Mattei, E., Meduri, C., Meli, P., Minelli, G., Nebuloni, M., Nistico, L., Nonis, M., Palmisano, L., Petrosillo, N., Pezzotti, P., Punzo, O., Puro, V., Rezza, G., Riccardo, F., Rota, M. C., Salerno, P., Serra, D., Siddu, A., Stefanelli, P., Tamburo DeBella, M., Tiple, D., Vaianella, L., Vichi, M., Zona, A., and Brusaferro, S.
- Subjects
Male ,Multivariate analysis ,covid-19 ,comorbidities ,in-hospital complications ,sex ,transition of care ,lcsh:Medicine ,Disease ,Comorbidity ,030204 cardiovascular system & hematology ,Comorbidities ,COVID-19 ,In-hospital complications ,Sex ,Transition of care ,lcsh:Physiology ,Aged ,Aged, 80 and over ,Betacoronavirus ,Coronavirus Infections ,Female ,Hospitalization ,Humans ,Italy ,Middle Aged ,Multimorbidity ,Multivariate Analysis ,Pandemics ,Patient Transfer ,Pneumonia, Viral ,Prevalence ,Retrospective Studies ,Risk Factors ,SARS-CoV-2 ,Sex Factors ,0302 clinical medicine ,Endocrinology ,80 and over ,030212 general & internal medicine ,Viral ,lcsh:QP1-981 ,Acute kidney injury ,medicine.medical_specialty ,NO ,Gender Studies ,03 medical and health sciences ,Internal medicine ,medicine ,Dementia ,business.industry ,Research ,lcsh:R ,Outbreak ,Retrospective cohort study ,Pneumonia ,medicine.disease ,business ,Kidney disease - Abstract
Background Among the unknowns posed by the coronavirus disease 2019 (COVID-19) outbreak, the role of biological sex to explain disease susceptibility and progression is still a matter of debate, with limited sex-disaggregated data available. Methods A retrospective analysis was performed to assess if sex differences exist in the clinical manifestations and transitions of care among hospitalized individuals dying with laboratory-confirmed SARS-CoV-2 infection in Italy (February 27–June 11, 2020). Clinical characteristics and the times from symptoms’ onset to admission, nasopharyngeal swab, and death were compared between sexes. Adjusted multivariate analysis was performed to identify the clinical features associated with male sex. Results Of the 32,938 COVID-19-related deaths that occurred in Italy, 3517 hospitalized and deceased individuals with COVID-19 (mean 78 ± 12 years, 33% women) were analyzed. At admission, men had a higher prevalence of ischemic heart disease (adj-OR = 1.76, 95% CI 1.39–2.23), chronic obstructive pulmonary disease (adj-OR = 1.7, 95% CI 1.29–2.27), and chronic kidney disease (adj-OR = 1.48, 95% CI 1.13–1.96), while women were older and more likely to have dementia (adj-OR = 0.73, 95% CI 0.55–0.95) and autoimmune diseases (adj-OR = 0.40, 95% CI 0.25–0.63), yet both sexes had a high level of multimorbidity. The times from symptoms’ onset to admission and nasopharyngeal swab were slightly longer in men despite a typical acute respiratory illness with more frequent fever at the onset. Men received more often experimental therapy (adj-OR = 2.89, 95% CI 1.45–5.74) and experienced more likely acute kidney injury (adj-OR = 1.47, 95% CI 1.13–1.90). Conclusions Men and women dying with COVID-19 had different clinical manifestations and transitions of care. Identifying sex-specific features in individuals with COVID-19 and fatal outcome might inform preventive strategies.
- Published
- 2020
7. Comparison of U.S. Hospital Costs Between Transcatheter Aortic Valve Replacement (TAVR) And Surgical Aortic Valve Replacement (SAVR)
- Author
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Meduri, C, primary, Chung, JK, additional, Gaffney, JC, additional, Henley, S, additional, Williams, JM, additional, and Gada, H, additional
- Published
- 2017
- Full Text
- View/download PDF
8. PMD43 - Comparison of U.S. Hospital Costs Between Transcatheter Aortic Valve Replacement (TAVR) And Surgical Aortic Valve Replacement (SAVR)
- Author
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Meduri, C, Chung, JK, Gaffney, JC, Henley, S, Williams, JM, and Gada, H
- Published
- 2017
- Full Text
- View/download PDF
9. Effects of cytokines and endotoxin on the intracellular growth of bacteria.
- Author
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Kanangat, S, Meduri, G U, Tolley, E A, Patterson, D R, Meduri, C U, Pak, C, Griffin, J P, Bronze, M S, and Schaberg, D R
- Abstract
Patients with unresolving acute respiratory distress syndrome (ARDS) have persistently elevated levels of proinflammatory cytokines in the lungs and circulation and increased rates of bacterial infections. Phagocytic cells hyperactivated with lipopolysaccharide (LPS), which induces high levels of proinflammatory cytokines in monocytic cells, are inefficient in killing ingested bacteria despite having intact phagocytic activity. On the other hand, phagocytic cells that are activated with an analogue of LPS that does not induce the expression of proinflammatory cytokines effectively ingest and kill bacteria. We hypothesized that in the presence of high concentrations of proinflammatory cytokines, bacteria may adapt and utilize cytokines to their growth advantage. To test our hypothesis, we primed a human monocytic cell line (U937) with escalating concentrations of the proinflammatory cytokines tumor necrosis factor alpha, interleukin-1beta (IL-1beta), and IL-6 and with LPS. These cells were then exposed to fresh isolates of three common nosocomial pathogens: Staphylococcus aureus, Pseudomonas aeruginosa, and an Acinetobacter sp. In human monocytes primed with lower concentrations of proinflammatory cytokines (10 to 250 pg) or LPS (1 and 10 ng), intracellular bacterial growth decreased. However, when human monocytes were primed with higher concentrations of proinflammatory cytokines (1 to 10 ng) or LPS (1 to 10 micrograms), intracellular growth of the tested bacteria increased significantly (P <0.0001). These results were reproduced with peripheral blood monocytes obtained from normal healthy volunteers. The specificity of the cytokine activity was demonstrated by neutralizing the cytokines with specific antibodies. Our findings provide a possible mechanism to explain the frequent development of bacterial infections in patients with an intense and protracted inflammatory response.
- Published
- 1999
10. The interrater and intrarater reliability of the Wisconsin Gait Scale when administered by physical therapists to individuals post-stroke.
- Author
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Wellmon R, Campbell SL, Rubertone JA, Ellison MA, King RM, Meduri C, Spatafore AE, Talley JM, and Van Dyke AC
- Published
- 2002
11. BASILICA Procedure Prior to Valve-in-Valve TAVR in a Supra-Annular TAV Prosthesis.
- Author
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Damlin A, Meduri C, Manouras A, Verouhis D, Linder R, Rück A, and Settergren M
- Abstract
An 80-year-old man with a supra-annular transcatheter aortic valve (TAV) prosthesis presented with severe transvalvular aortic regurgitation 18 months after the TAV replacement procedure. The authors report the first ever valve-in-valve procedure using BASILICA (bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction) in such a supra-annular TAV prosthesis. Minimal paravalvular leakage, normal coronary artery flow, and easy coronary access were seen postimplantation. ( Level of Difficulty: Advanced. )., Competing Interests: Dr Damlin has received speaker compensation from Edwards Lifesciences. Drs Settergren, Meduri, Rück, and Linder serve as proctors for Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)
- Published
- 2023
- Full Text
- View/download PDF
12. Imaging for Tricuspid Valve Repair and Replacement.
- Author
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Agricola E, Asmarats L, Maisano F, Cavalcante JL, Liu S, Milla F, Meduri C, Rodés-Cabau J, Vannan M, and Pibarot P
- Subjects
- Humans, Predictive Value of Tests, Severity of Illness Index, Treatment Outcome, Heart Valve Prosthesis Implantation, Tricuspid Valve surgery, Tricuspid Valve Insufficiency surgery
- Abstract
Primary or secondary tricuspid regurgitation (TR) represents an important health care burden and challenge which has often been neglected or undertreated in the past. The expansion and reinforcement of the indications for tricuspid valve (TV) intervention in the 2017 editions of the guidelines as well as the introduction of transcatheter tricuspid valve intervention (TTVI) has considerably increased the attention of the community on the TV and the volume of TV interventions in the past years. Depending on the anatomic target, TTVI can be categorized as the following: 1) direct or indirect tricuspid restrictive annuloplasty; 2) direct (edge-to-edge repair) or indirect (coaptation device) restoration of leaflet coaptation; 3) heterotopic tricuspid valve implantation; and 4) transcatheter tricuspid valve replacement. Multimodality imaging has crucial role for the following: 1) patient selection for TTVI and procedure planning; 2) guiding and monitoring the procedure; and 3) assessing and following over time the results of the procedure. The key points for pre-procedural imaging are: 1) accurate quantitation of TR severity; 2) proper identification of the mechanism(s) responsible for the TR; and 3) quantitation of RV dysfunction and pulmonary arterial hypertension. This imaging work-up is essential to select the right type of intervention for the right patient and TV. Transesophageal echocardiography and fluoroscopy imaging is also key for guiding the TTVI procedures and fusion between these 2 modalities may further enhance the quality of procedure guiding., Competing Interests: Author Disclosures Dr. Pibarot has received funding from Edwards Lifesciences for echocardiography corelab analyses in the field of transcatheter valve therapies with no personal compensation. Dr. Rodés-Cabau is a consultant for and has received institutional research grants from V-Wave. Dr. Maisano is a consultant for Abbott Vascular, ValtechCardio, Medtronic, Edwards Lifesciences, and Apica; is a founder of 4Tech; and has received royalties from Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
13. Early Experience With New Transcatheter Mitral Valve Replacement.
- Author
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Bapat V, Rajagopal V, Meduri C, Farivar RS, Walton A, Duffy SJ, Gooley R, Almeida A, Reardon MJ, Kleiman NS, Spargias K, Pattakos S, Ng MK, Wilson M, Adams DH, Leon M, Mack MJ, Chenoweth S, and Sorajja P
- Subjects
- Aged, Aged, 80 and over, Cardiac Catheterization methods, Echocardiography methods, Female, Humans, Male, Mitral Valve Insufficiency diagnosis, Mitral Valve Insufficiency physiopathology, Outcome and Process Assessment, Health Care, Risk Factors, Severity of Illness Index, Time Factors, Treatment Outcome, Ventricular Function, Left, Heart Valve Prosthesis adverse effects, Heart Valve Prosthesis Implantation adverse effects, Heart Valve Prosthesis Implantation instrumentation, Heart Valve Prosthesis Implantation methods, Mitral Valve diagnostic imaging, Mitral Valve surgery, Mitral Valve Insufficiency surgery, Postoperative Complications diagnosis, Postoperative Complications mortality, Postoperative Complications physiopathology
- Abstract
Background: Transcatheter mitral valve replacement (TMVR) is a potential therapy for patients with symptomatic, severe mitral regurgitation (MR). The feasibility of this therapy remains to be defined., Objectives: The authors report their early experience with TMVR using a new valve system., Methods: The valve is a self-expanding, nitinol valve with bovine pericardial leaflets that is placed using a transapical delivery system. Patients with symptomatic MR who were deemed high or extreme risk by the local heart teams were enrolled in a global pilot study at 14 sites (United States, Australia, and Europe)., Results: Fifty consecutively enrolled patients (mean age: 73 ± 9 years; 58.0% men; 84% secondary MR) underwent TMVR with the valve. The mean Society for Thoracic Surgery score was 6.4 ± 5.5%; 86% of patients were New York Heart Association functional class III or IV, and the mean left ventricular ejection fraction was 43 ± 12%. Device implant was successful in 48 patients with a median deployment time of 14 min (interquartile range: 12 to 17 min). The 30-day mortality was 14%, with no disabling strokes, or repeat interventions. Median follow-up was 173 days (interquartile range: 54 to 342 days). At latest follow-up, echocardiography confirmed mild or no residual MR in all patients who received implants. Improvements in symptom class (79% in New York Heart Association functional class I or II at follow-up; p < 0.0001 vs. baseline) and Minnesota Heart Failure Questionnaire scores (56.2 ± 26.8 vs. 31.7 ± 22.1; p = 0.011) were observed., Conclusions: TMVR with the valve was feasible in a study group at high or extreme risk for conventional mitral valve replacement. These results inform trial design of TMVR in lower-risk patients with severe mitral valve regurgitation (Evaluation of the Safety and Performance of the Twelve Intrepid Transcatheter Mitral Valve Replacement System in High Risk Patients with Severe, Symptomatic Mitral Regurgitation - The Twelve Intrepid TMVR Pilot Study; NCT02322840)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
14. Quantitative Prediction of Paravalvular Leak in Transcatheter Aortic Valve Replacement Based on Tissue-Mimicking 3D Printing.
- Author
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Qian Z, Wang K, Liu S, Zhou X, Rajagopal V, Meduri C, Kauten JR, Chang YH, Wu C, Zhang C, Wang B, and Vannan MA
- Subjects
- Aged, Aged, 80 and over, Aortic Valve diagnostic imaging, Aortic Valve physiopathology, Aortic Valve Insufficiency diagnostic imaging, Aortic Valve Insufficiency physiopathology, Aortic Valve Stenosis diagnostic imaging, Aortic Valve Stenosis physiopathology, Feasibility Studies, Female, Heart Valve Prosthesis, Hemodynamics, Humans, Male, Phantoms, Imaging, Predictive Value of Tests, Proof of Concept Study, Prosthesis Design, Radiographic Image Interpretation, Computer-Assisted, Retrospective Studies, Risk Assessment, Risk Factors, Stress, Mechanical, Transcatheter Aortic Valve Replacement instrumentation, Treatment Outcome, Aortic Valve surgery, Aortic Valve Insufficiency etiology, Aortic Valve Stenosis surgery, Models, Cardiovascular, Patient-Specific Modeling, Printing, Three-Dimensional, Tomography, X-Ray Computed instrumentation, Transcatheter Aortic Valve Replacement adverse effects
- Abstract
Objectives: This study aimed to develop a procedure simulation platform for in vitro transcatheter aortic valve replacement (TAVR) using patient-specific 3-dimensional (3D) printed tissue-mimicking phantoms. We investigated the feasibility of using these 3D printed phantoms to quantitatively predict the occurrence, severity, and location of any degree of post-TAVR paravalvular leaks (PVL)., Background: We have previously shown that metamaterial 3D printing technique can be used to create patient-specific phantoms that mimic the mechanical properties of biological tissue. This may have applications in procedural planning for cardiovascular interventions., Methods: This retrospective study looked at 18 patients who underwent TAVR. Patient-specific aortic root phantoms were created using the tissue-mimicking 3D printing technique using pre-TAVR computed tomography. The CoreValve (self-expanding valve) prostheses were deployed in the phantoms to simulate the TAVR procedure, from which post-TAVR aortic root strain was quantified in vitro. A novel index, the annular bulge index, was measured to assess the post-TAVR annular strain unevenness in the phantoms. We tested the comparative predictive value of the bulge index and other known predictors of post-TAVR PVL., Results: The maximum annular bulge index was significantly different among patient subgroups that had no PVL, trace-to-mild PVL, and moderate-to-severe PVL (p = 0.001). Compared with other known PVL predictors, bulge index was the only significant predictor of moderate-severe PVL (area under the curve = 95%; p < 0.0001). Also, in 12 patients with post-TAVR PVL, the annular bulge index predicted the major PVL location in 9 patients (accuracy = 75%)., Conclusions: In this proof-of-concept study, we have demonstrated the feasibility of using 3D printed tissue-mimicking phantoms to quantitatively assess the post-TAVR aortic root strain in vitro. A novel indicator of the post-TAVR annular strain unevenness, the annular bulge index, outperformed the other established variables and achieved a high level of accuracy in predicting post-TAVR PVL, in terms of its occurrence, severity, and location., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
15. Effects of methylprednisolone on intracellular bacterial growth.
- Author
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Meduri GU, Kanangat S, Bronze M, Patterson DR, Meduri CU, Pak C, Tolley EA, and Schaberg DR
- Subjects
- Acinetobacter drug effects, Acinetobacter growth & development, Dose-Response Relationship, Drug, Gene Expression drug effects, Gene Expression immunology, Humans, In Vitro Techniques, Interleukin-1 genetics, Interleukin-6 genetics, Lipopolysaccharides pharmacology, Monocytes drug effects, Monocytes immunology, Monocytes microbiology, Phagocytosis immunology, Pseudomonas aeruginosa drug effects, Pseudomonas aeruginosa growth & development, RNA, Messenger analysis, Staphylococcus aureus drug effects, Staphylococcus aureus growth & development, Tumor Necrosis Factor-alpha genetics, U937 Cells, Anti-Inflammatory Agents pharmacology, Bacteria drug effects, Bacteria growth & development, Methylprednisolone pharmacology
- Abstract
Clinical studies have shown positive associations among sustained and intense inflammatory responses and the incidence of bacterial infections. Patients presenting with acute respiratory distress syndrome (ARDS) and high levels of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and IL-6, have increased risk for developing nosocomial infections attributable to organisms such as Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter spp., compared to those patients with lower levels. Our previous in vitro studies have demonstrated that these bacterial strains exhibit enhanced growth extracellularly when supplemented with high concentrations of pure recombinant TNF-alpha, IL-1 beta, or IL-6. In addition, we have shown that the intracellular milieu of phagocytic cells that are exposed to supraoptimal concentrations of TNF-alpha, IL-1 beta, and IL-6 or lipopolysaccharide (LPS) favors survival and replication of ingested bacteria. Therefore, we hypothesized that under conditions of intense inflammation the host's micromilieu favors bacterial infections by exposing phagocytic cells to protracted high levels of inflammatory cytokines. Our clinical studies have shown that methylprednisolone is capable of reducing the levels of TNF-alpha, IL-1 beta, and IL-6 in ARDS patients. Hence, we designed a series of in vitro experiments to test whether human monocytic cells (U937 cells) that are activated with high concentrations of LPS, which upregulate the release of proinflammatory cytokines from these phagocytic cells, would effectively kill or restrict bacterial survival and replication after exposure to methylprednisolone. Fresh isolates of S. aureus, P. aeruginosa, and Acinetobacter were used in our studies. Our results indicate that, compared with the control, stimulation of U937 cells with 100-ng/ml, 1.0-microg/ml, 5.0-microg/ml, or 10.0-microg/ml concentrations of LPS enhanced the intracellular survival and replication of all three species of bacteria significantly (for all, P = 0.0001). Stimulation with < or =10.0 ng of LPS generally resulted in efficient killing of the ingested bacteria. Interestingly, when exposed to graded concentrations of methylprednisolone, U937 cells that had been stimulated with 10.0 microg of LPS were able to suppress bacterial replication efficiently in a concentration-dependent manner. Significant reduction in numbers of CFU was observed at > or =150 microg of methylprednisolone per ml (P values were 0.032, 0.008, and 0.009 for S. aureus, P. aeruginosa, and Acinetobacter, respectively). We have also shown that steady-state mRNA levels of TNF-alpha, IL-1 beta, and IL-6 in LPS-activated cells were reduced by treatment of such cells with methylprednisolone, in a concentration-dependent manner. The effective dose of methylprednisolone was 175 mg, a value that appeared to be independent of priming level of LPS and type of mRNA. We therefore postulate that a U-shaped relationship exists between the level of expression of TNF-alpha, IL-1 beta, and IL-6 within the phagocytic cells and their abilities to suppress active survival and replication of phagocytized bacteria.
- Published
- 2001
- Full Text
- View/download PDF
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