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Evidence for a role for Galphai1 in mediating weak agonist-induced platelet aggregation in human platelets: reduced Galphai1 expression and defective Gi signaling in the platelets of a patient with a chronic bleeding disorder 总被引:2,自引:0,他引:2 下载免费PDF全文
Patel YM Patel K Rahman S Smith MP Spooner G Sumathipala R Mitchell M Flynn G Aitken A Savidge G 《Blood》2003,101(12):4828-4835
We have examined platelet functional responses and characterized a novel signaling defect in the platelets of a patient suffering from a chronic bleeding disorder. Platelet aggregation responses stimulated by weak agonists such as adenosine diphosphate (ADP) and adrenaline were severely impaired. In comparison, both aggregation and dense granule secretion were normal following activation with high doses of collagen, thrombin, or phorbol-12 myristate-13 acetate (PMA). ADP, thrombin, or thromboxane A2 (TxA2) signaling through their respective Gq-coupled receptors was normal as assessed by measuring either mobilization of intracellular calcium, diacylglycerol (DAG) generation, or pleckstrin phosphorylation. In comparison, Gi-mediated signaling induced by either thrombin, ADP, or adrenaline, examined by suppression of forskolin-stimulated rise in cyclic AMP (cAMP) was impaired, indicating dysfunctional Galphai signaling. Immunoblot analysis of platelet membranes with specific antiserum against different Galpha subunits indicated normal levels of Galphai2,Galphai3,Galphaz, and Galphaq in patient platelets. However, the Galphai1level was reduced to 25% of that found in normal platelets. Analysis of platelet cDNA and gDNA revealed no abnormality in either the Galphai1 or Galphai2 gene sequences. Our studies implicate the minor expressed Galphai subtype Galphai1 as having an important role in regulating signaling pathways associated with the activation of alphaIIbbeta3 and subsequent platelet aggregation by weak agonists. 相似文献
64.
Strain-specific immune response to Haemophilus influenzae in chronic obstructive pulmonary disease 总被引:7,自引:0,他引:7
Sethi S Wrona C Grant BJ Murphy TF 《American journal of respiratory and critical care medicine》2004,169(4):448-453
Previous studies of immune response to Haemophilus influenzae after exacerbations of chronic obstructive pulmonary disease (COPD) have yielded contradictory results. Using homologous (infecting) strains and immunoassays to surface-exposed epitopes, we tested the hypothesis that adults with COPD make new antibodies to strain-specific, surface-exposed epitopes on H. influenzae after exacerbations. We collected clinical information, sputum, and serum monthly and during exacerbations from 81 patients with COPD over 56 months. Serum antibodies to H. influenzae after exacerbations associated with H. influenzae in sputum were detected with whole bacterial cell ELISA and bactericidal assays. An immune response to homologous H. influenzae occurred after 22 of 36 (61.1%) exacerbations with newly acquired strains compared with 7 of 33 (21.2%) exacerbations with preexisting strains (odds ratio [OR] = 4.4; 95%, 1.8 to 10.8; p = 0.001). An absence of an immune response was strongly associated with complement sensitivity (OR = 0.03; 95% confidence interval, 0.003 to 0.22; p = 0.001). New bactericidal antibodies developed after exacerbations were highly strain specific, showing bactericidal activity for only 11 of 90 (12.2%) heterologous strains. Development of an immune response to H. influenzae supports its role in causing exacerbations. The strain specificity of the immune response likely represents a mechanism of recurrent exacerbations. 相似文献
65.
Measurement and correlation of wedged hepatic, intrahepatic, intrasplenic and intravariceal pressures in patients with cirrhosis of liver and non-cirrhotic portal fibrosis. 总被引:2,自引:1,他引:2 下载免费PDF全文
In order to examine the relationship of various haemodynamic parameters in two different liver diseases, 10 patients with cirrhosis of liver and 14 patients with non-cirrhotic portal fibrosis were studied. In cirrhotics, mean (+/- SD) wedged hepatic (25.8 +/- 6.4 mmHg), intrahepatic (24.5 +/- 6.2 mmHg) and intrasplenic (25.0 +/- 5.6 mmHg) pressures correlated significantly (p less than 0.001) with intravariceal (25.2 +/- 6.7) pressure measurements. In patients with NCPF, mean (+/- SD) wedged hepatic (9.1 +/- 3.7 mmHg) and intraphepatic (15.4 +/- 5.8 mmHg) pressures were significantly (p less than 0.01) lower than the intrasplenic (24.5 +/- 4.2 mmHg) and intravariceal (23.96 +/- 5.6 mmHg) pressures. Two independent pressure gradients, one between intrasplenic and intrahepatic pressure (8.9 +/- 6.5 mmHg) and another between intrahepatic and wedged hepatic venous pressure (6.2 +/- 5.6 mmHg) were seen in non-cirrhotic portal fibrosis patients, indicating the likelihood of both pre- and perisinusoidal resistance to flow of portal venous blood in these patients. A highly significant (p less than 0.001) correlation between intravariceal and intrasplenic pressures was found in patients with cirrhosis of liver (r = 0.93), as well as in patients with non-cirrhotic portal fibrosis (r = 0.85). No correlation was found between the size of oesophageal varices and wedged hepatic and intrahepatic pressures. Patients with grade 4 varices had significantly higher intravariceal (p less than 0.01) and intrasplenic (p less than 0.05) pressure than patients with grade 2 varices. It can be concluded that intravariceal pressure is representative of portal pressure in patients with cirrhosis of liver as well as in non-cirrhotic portal fibrosis patients and it can be recommended as the single haemodynamic investigation in patients with portal hypertension and oesophageal varices. 相似文献
66.
Vasanth Sathiyakumar Rachel V. Thakore Daniel J. Stinner William T. Obremskey James R. Ficke Manish K. Sethi 《Current reviews in musculoskeletal medicine》2015,8(3):276-289
The use of antibiotic prophylaxis and debridement is controversial when treating low- and high-velocity gunshot-induced fractures, and established treatment guidelines are currently unavailable. The purpose of this review was to evaluate the literature for the prophylactic antibiotic and debridement policies for (1) low-velocity gunshot fractures of the extremities, joints, and pelvis and (2) high-velocity gunshot fractures of the extremities. Low-velocity gunshot fractures of the extremities were subcategorized into operative and non-operative cases, whereas low-velocity gunshot fractures of the joints and pelvis were evaluated based on the presence or absence of concomitant bowel injury. In the absence of surgical necessity for fracture care such as concomitant absence of gross wound contamination, vascular injury, large soft-tissue defect, or associated compartment syndrome, the literature suggests that superficial debridement for low-velocity ballistic fractures with administration of antibiotics is a satisfactory alternative to extensive operative irrigation and debridement. In operative cases or those involving bowel injuries secondary to pelvic fractures, the literature provides support for and against extensive debridement but does suggest the use of intravenous antibiotics. For high-velocity ballistic injuries, the literature points towards the practice of extensive immediate debridement with prophylactic intravenous antibiotics. Our systematic review demonstrates weak evidence for superficial debridement of low-velocity ballistic fractures, extensive debridement for high-velocity ballistic injuries, and antibiotic use for both types of injury. Intra-articular fractures seem to warrant debridement, while pelvic fractures with bowel injury have conflicting evidence for debridement but stronger evidence for antibiotic use. Given a relatively low number of studies on this subject, we recommend that further high-quality research on the debridement and antibiotic use for gunshot-induced fractures of the extremities should be conducted before definitive recommendations and guidelines are developed.
Electronic supplementary material
The online version of this article (doi:10.1007/s12178-015-9284-9) contains supplementary material, which is available to authorized users. 相似文献67.
Daniel J. Johnson Sarah E. Greenberg Vasanth Sathiyakumar Rachel Thakore Jesse M. Ehrenfeld William T. Obremskey Manish K. Sethi 《Journal of orthopaedics and traumatology》2015,16(3):209-213
BackgroundThe aim of this study is to investigate how the Charlson Comorbidity Index (CCI) scores contribute to increased length of stay (LOS) and healthcare costs in hip fracture patients.ResultsMultivariate linear regression analysis modeled the length of stay as a function of CCI score. Each unit increase in the CCI score corresponded to an increase in length of hospital stay and hospital costs incurred [effect size = 0.21; (0.0434–0.381); p = 0.014]. Patients with a CCI score of 2 (compared to a baseline CCI score of 0), on average, stayed 1.92 extra days in the hospital, and incurred $8,697.60 extra costs.ConclusionsThe CCI score is associated with length of stay and hospital costs incurred following treatment for hip fracture. The CCI score may be a useful tool for risk assessment in bundled payment plans.
Level of evidence
Level III. 相似文献68.
Desikan R Barlogie B Sethi R Toor A Spoon D Angtuaco E Vanhemert R VijayaGopal A Singhal S Mehta J Jagannath S Munshi N Zangari M Fassas A Tricot G Anaissie E 《British journal of haematology》2003,120(6):1047-1050
Bone pain, especially back pain, is a common presenting feature of myeloma patients. We report three multiple myeloma patients with exacerbations of back pain and referred shoulder pain resulting from vertebral infections. Two patients were treated with surgery, and one patient had computerized tomography-guided percutaneous needle aspiration for diagnostic purposes. All three patients received a prolonged course of antibiotics. Vertebral infection resolved with this treatment in all three patients without any recurrence. Previous dexamethasone therapy, together with an episode of bacteraemia, appears to be a predisposing factor for vertebral infection. Magnetic resonance imaging enabled the diagnosis in all three patients. 相似文献
69.
Yatin Mehta Abhinav Gupta Subhash Todi SN Myatra D. P. Samaddar Vijaya Patil Pradip Kumar Bhattacharya Suresh Ramasubban 《Indian Journal of Critical Care Medicine》2014,18(3):149-163
These guidelines, written for clinicians, contains evidence-based recommendations for the prevention of hospital acquired infections Hospital acquired infections are a major cause of mortality and morbidity and provide challenge to clinicians. Measures of infection control include identifying patients at risk of nosocomial infections, observing hand hygiene, following standard precautions to reduce transmission and strategies to reduce VAP, CR-BSI, CAUTI. Environmental factors and architectural lay out also need to be emphasized upon. Infection prevention in special subsets of patients - burns patients, include identifying sources of organism, identification of organisms, isolation if required, antibiotic prophylaxis to be used selectively, early removal of necrotic tissue, prevention of tetanus, early nutrition and surveillance. Immunodeficient and Transplant recipients are at a higher risk of opportunistic infections. The post tranplant timetable is divided into three time periods for determining risk of infections. Room ventilation, cleaning and decontamination, protective clothing with care regarding food requires special consideration. Monitoring and Surveillance are prioritized depending upon the needs. Designated infection control teams should supervise the process and help in collection and compilation of data. Antibiotic Stewardship Recommendations include constituting a team, close coordination between teams, audit, formulary restriction, de-escalation, optimizing dosing, active use of information technology among other measure. The recommendations in these guidelines are intended to support, and not replace, good clinical judgment. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. 相似文献
70.
Dinesh Raj Rakesh Lodha Aparna Mukherjee Tavpritesh Sethi Anurag Agrawal Sushil Kumar Kabra 《Indian pediatrics》2014,51(2):105-111