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排序方式: 共有475条查询结果,搜索用时 15 毫秒
41.
Safdar Z Wang P Ichimura H Issekutz AC Quadri S Bhattacharya J 《The Journal of clinical investigation》2003,112(10):1541-1549
Although capillary barrier deterioration underlies major inflammatory lung pathology, barrier-enhancing strategies are not available. To consider hyperosmolar therapy as a possible strategy, we gave 15-minute infusions of hyperosmolar sucrose in lung venular capillaries imaged in real time. Surprisingly, this treatment enhanced the capillary barrier, as indicated by quantification of the capillary hydraulic conductivity. The barrier enhancement was sufficient to block the injurious effects of thrombin, TNF-alpha, and H2O2 in single capillaries, and of intratracheal acid instillation in the whole lung. Capillary immunofluorescence indicated that the hyperosmolar infusion markedly augmented actin filament formation and E-cadherin expression at the endothelial cell periphery. The actin-depolymerizing agent latrunculin B abrogated the hyperosmolar barrier enhancement as well as the actin filament formation, suggesting a role for actin in the barrier response. Furthermore, hyperosmolar infusion blocked TNF-alpha-induced P-selectin expression in an actin-dependent manner. Our results provide the first evidence to our knowledge that in lung capillaries, hyperosmolarity remodels the endothelial barrier and the actin cytoskeleton to enhance barrier properties and block proinflammatory secretory processes. Hyperosmolar therapy may be beneficial in lung inflammatory disease. 相似文献
42.
Virk Sohrab S. Diwan Ashish Phillips Frank M. Sandhu Harvinder Khan Safdar N. 《Clinical orthopaedics and related research》2017,475(11):2752-2762
Clinical Orthopaedics and Related Research® - Lumbar discectomy has been shown to be clinically beneficial in numerous studies for appropriately selected patients. Some patients, however,... 相似文献
43.
Nasia Safdar MD Christopher J. Crnich MD Dennis G. Maki MD 《Current infectious disease reports》2001,3(6):487-495
Modern day health care has become synonymous with cutting-edge, high-tech medicine, which includes a large and growing number of invasive medical devices, especially in intensive care units. The most widely used of these devices—intravascular catheters of many types and urinary catheters—account for more than one half of all institutionally acquired infections. Growing knowledge of the pathogenesis and epidemiology of these infections has given birth to novel and more effective control measures, the most promising of which are technologically based. 相似文献
44.
Osama Y Safdar Rana M Baghdadi Sereen A Alahmadi Bana E Fakieh Amaal M Algaydi 《World Journal of Clinical Pediatrics》2022,11(1):14-26
Whether the underlying mutations are homozygous, heterozygous, or co-inherited with other hemoglobinopathies, sickle cell disease is known to afflict the kidneys, leading to the clinical entity known as sickle cell nephropathy (SCN). Although common, SCN remains diagnostically elusive. Conventional studies performed in the context of renal disorders often fail to detect early stage SCN. This makes the quest for early diagnosis and treatment more challenging, and it increases the burden of chronic kidney disease-related morbidity among patients. Novel diagnostic tools have been employed to overcome this limitation. In this study, we discuss various biomarkers of SCN, including those employed in clinical practice and others recently identified in experimental settings, such as markers of vascular injury, endothelial dysfunction, tubulo-glomerular damage, and oxidative stress. These include kidney injury molecule-1, monocyte chemoattractant protein-1, N-acetyl-B-D-glucosaminidase, ceruloplasmin, orosomucoid, nephrin, and cation channels, among others. Furthermore, we explore the potential of novel biomarkers for refining diagnostic and therapeutic approaches and describe some obstacles that still need to be overcome. We highlight the importance of a collaborative approach to standardize the use of promising new biomarkers. Finally, we outline the limitations of conventional markers of renal damage as extensions of the pathogenic process occurring at the level of the organ and its functional subunits, with a discussion of the expected pattern of clinical and biochemical progression among patients with SCN. 相似文献
45.
D. E. Ghannam G. H. Rodriguez I. I. Raad A. Safdar 《European journal of clinical microbiology & infectious diseases》2009,28(3):253-259
We sought to evaluate the safety and feasibility of inhaled aminoglycosides or colistin in cancer patients with ventilator-associated
pneumonia (VAP) due to Gram-negative bacteria (GNB). A retrospective case-matched study was obtained after obtaining IRB approval
in patients at the intensive care unit at our NCI-designated comprehensive cancer center between 1999 and 2005. Sixteen patients
with GNB-VAP who received inhaled aminoglycosides or colistin were compared with 16 patients who had received these antibiotics
intravenously alone. Eligible patients were required to have received at least six doses of inhaled therapy, or 3 or more
days of intravenous therapy. Clinical Pulmonary Infection Scores were used to assess pneumonia severity. Standard ATS criteria
were used to define VAP. Patients treated with inhaled antibiotics were less likely to have received corticosteroids (13%
vs 50%; P < 0.02) and had a higher median baseline creatinine level (0.85 vs 0.6 mg/dL; P < 0.02) than patients treated intravenously. Pseudomonas aeruginosa (69%) was the most common cause of VAP. There were no serious adverse events associated with inhaled antibiotics. Patients
who received these antibiotics intravenously developed renal dysfunction (31%); none of the patients treated with inhaled
antibiotics developed nephrotoxicity (P ≤ 0.04). Patients treated with inhaled antibiotics were more likely to have complete resolution of clinical (81% vs 31% in
the intravenous antibiotic group; P < 0.01) and microbiologic infection (77% vs 8% in the intravenous antibiotic group: P < 0.0006). In a multivariate analysis adjusted for corticosteroid use, inhaled antibiotic therapy was predictive of complete
clinical resolution (odds ratio [OR], 6.3; 95% confidence interval [CI], 1.1, 37.6; P < 0.04) and eradication of causative organisms (OR 36.7; 95% CI, 3.3, 412.2; P < 0.003). In critically ill cancer patients with Gram-negative VAP, inhaled aminoglycosides were tolerated without serious
toxicity and may lead to improved outcome.
A portion of this study was presented at the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, 27–30
September 2006, San Francisco [abstract K-0288]. 相似文献
46.
Basmah Safdar Gail D’Onofrio James Dziura Raymond R. Russell Caitlin Johnson Albert J. Sinusas 《Clinical therapeutics》2017,39(1):55-63
Purpose
Coronary microvascular dysfunction (CMD) is a common but underdiagnosed cause of chest pain. Literature is scant regarding effective treatments. We explored the effect of ranolazine on coronary flow reserve (CFR) among symptomatic patients with CMD.Methods
This pilot double-blinded randomized controlled trial included emergency department patients with chest pain and CMD admitted to an observation unit between June 2014 and November 2015. Participants were assessed by cardiac Rb-82 positron emission tomography and computed tomography imaging at baseline and 30 days. CMD was defined as CFR <2 corrected for rate pressure product or <2.5 uncorrected, with no evidence of obstructive or nonobstructive coronary artery disease or calcification. Patients with infarction, hypertensive urgency, heart failure, or prescribed QTc-prolonging drugs were excluded. Participants were assigned to ranolazine or placebo in a 2:1 ratio. Primary outcome was change in CFR at 30 days.Findings
We enrolled 31 patients (71% female, mean [SD] age 50 [6] years) with CMD (mean [SD] corrected CFR 1.6 [0.3]). Ranolazine improved CFR at 30 days by 17% (P = 0.005) compared with 0% with placebo (P = 0.67). However, there was no significant difference in the primary outcome as measured by mean change in CFR (0.27 ranolazine compared with 0.06 placebo; 95% CI, ?0.08 to 0.62).Implications
The emergency department offers a unique venue to diagnose CMD with acute symptoms. In an exploratory randomized controlled trial of symptomatic patients with CMD and no coronary artery disease, promising results were seem with ranolazine and CFR improving at 30 days. Large robust clinical trials are needed to verify improvement of CMD in a sex-specific model. ClinicalTrials.gov identifier NCT02052011. 相似文献47.
H.-Y. Sun J. M. Aguado H. Bonatti G. Forrest K. L. Gupta N. Safdar G. T. John K. J. Pursell P. Muñoz R. Patel J. Fortun P. Martin-Davila B. Philippe F. Philit A. Tabah N. Terzi V. Chatelet S. Kusne N. Clark E. Blumberg M. B. Julia A. Humar S. Houston C. Lass-Florl L. Johnson E. R. Dubberke M. A. Barron O. Lortholary N. Singh the Zygomycosis Transplant Study Group 《American journal of transplantation》2009,9(9):2166-2171
Fifty-eight solid organ transplant recipients with zygomycosis were studied to assess the presentation, radiographic characteristics, risks for extra-pulmonary dissemination and mortality of pulmonary zygomycosis. Pulmonary zygomycosis was documented in 31 patients (53%) and developed a median of 5.5 months (interquartile range, 2–11 months) posttransplantation. In all, 74.2% (23/31) of the patients had zygomycosis limited to the lungs and 25.8% (8/31) had lung disease as part of disseminated zygomycosis; cutaneous/soft tissue (50%, 4/8) was the most common site of dissemination. Pulmonary disease presented most frequently as consolidation/mass lesions (29.0%), nodules (25.8%) and cavities (22.6%). Patients with disseminated disease were more likely to have Mycocladus corymbifer as the causative pathogen. The mortality rate at 90 days after the treatment was 45.2%. In summary, pulmonary zygomycosis is the most common manifestation in solid organ transplant recipients with zygomycosis, and disseminated disease often involves the cutaneous/soft tissue sites but not the brain. 相似文献
48.
Safdar A Rodriguez G Rolston KV O'Brien S Khouri IF Shpall EJ Keating MJ Kantarjian HM Champlin RE Raad II Kontoyiannis DP 《Bone marrow transplantation》2007,39(3):157-164
Pneumocandins have concentration-dependent antifungal activity and higher dose of caspofungin (HD-CAP) in combination with other licensed antifungal therapy (OLAT) may improve response. Thirty-four patients who received HD-CAP were compared with 63 patients who received standard dose (SD)-CAP. There were no differences between the groups in either patient or disease characteristics. Significantly more patients in the HD-CAP arm had extrapulmonary infections (29 vs 8% in SD group; P=0.0053), and non-Aspergillus species infection (21 vs 6%; P=0.05) and had received prior antifungal therapy (71 vs 33%; P=0.0004). No serious adverse reactions were noted in patients receiving HD- or SD-CAP therapy. Twelve weeks after treatment commenced 44% had a complete or partial response compared with 29% in SD-CAP group (P=0.1). Logistic regression analysis showed a significant probability of a favorable outcome at 12 weeks in patients who received HD-CAP (OR 3.066, 95% CI, 1.092-8.61; P=0.033). This may in part reflect higher number of patients in HD group had received granulocyte-macrophage colony-stimulating factor (41 vs 14% in SD group; P=0.04) and/or interferon gamma (26 vs 5% in SD group; P=0.003) immune enhancement. Further studies are needed to evaluate efficacy of HD-CAP in severely immunosuppressed cancer patients with invasive fungal infections. 相似文献
49.
Amar Safdar William K. Decker Sufang Li Dongxia Xing Simon N. Robinson Hong Yang David Steiner Gilhen Rodriguez Elizabeth J. Shpall Catherine Bollard 《Vaccine》2009
Cancer patients and recipients of hematopoietic stem cell transplantation exhibit a negligible response to influenza vaccine. Toward the goal of addressing this issue, we developed an in vitro model of dendritic cell (DC) immunotherapy utilizing DCs generated from naïve umbilical cord blood (UCB). UCB DCs were loaded with purified rHA protein and used to stimulate autologous T-lymphocytes. Upon recall with HA-loaded autologous DC, a 4–10-fold increase in the number of IFN-γ producing T-lymphocytes was observed in comparison to T-cells stimulated with control DCs. Antigen-specific T-cell functionality was determined by 51Cr lytic assay. Using a peptide library of predicted HA binding epitopes, we mapped an HA-specific, DR15-restricted CD4 T-cell epitope and observed tetramer positive cells. This model demonstrates that HA-specific immune responses might possibly be generated in a de novo fashion and suggests that dendritic cell immunotherapy for the prevention of influenza in populations of immunosuppressed individuals could be feasible. 相似文献
50.