Translational research : the journal of laboratory and clinical medicine
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Posttraumatic coagulopathy is a major cause of morbidity. This prospective study evaluated the thrombelastography (TEG) system and PlateletMapping (Haemoscope Corporation, Niles, Ill) values posttrauma, and it correlated those values with transfusions and fatalities. After institutional review board approval, assays were performed on 161 trauma patients. ⋯ The abnormal TEG System parameters correlated with fatality. These coagulopathies were already evident OS. The TEG assays can assess coagulopathy, platelet dysfunction, and hyperfibrinolysis at an early stage posttrauma and suggest more effective interventions.
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The alveolar-capillary membrane serves as a barrier that prevents the accumulation of fluid in the alveolar space and restricts the diffusion of large solutes while facilitating an efficient gas exchange. When this barrier becomes dysfunctional, patients develop acute lung injury (ALI), which is characterized by pulmonary edema and increased lung inflammation that leads to a life-threatening impairment of gas exchange. In addition to the increase of inflammatory cytokines, plasma levels of endothelin-1 (ET-1), which is a primarily endothelium-derived vasoconstrictor, are increased in patients with ALI. ⋯ AFC involves active transport mechanisms where sodium (Na(+)) is actively transported from the alveolar airspaces, across the alveolar epithelium, and into the pulmonary circulation, which creates an osmotic gradient that is responsible for the clearance of lung edema. In this article, we review the relevance of ET-1 in the development of ALI, not only as a vasoconstrictor molecule but also by inhibiting AFC via the activation of endothelial ET-B receptors and generation. Furthermore, this review highlights the therapeutic role of drugs such as beta-adrenergic agonists and, in particular, of endothelin receptor antagonists in patients with ALI.
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Randomized Controlled Trial Clinical Trial
Intra-articular botulinum toxin A for refractory shoulder pain: a randomized, double-blinded, placebo-controlled trial.
We compared the short-term efficacy and safety of intra-articular (IA) botulinum toxin A (BoNT/A) to IA-placebo in patients with chronic, refractory shoulder joint pain. Forty-three shoulder joints in patients with moderate-to-severe shoulder arthritis pain were randomized to receive (1) 100 units IA-BoNT/A + lidocaine or (2) IA-saline + lidocaine. The following outcomes were compared using analysis of covariance: (1) primary: change in pain severity on a visual analog scale at 1 month (VAS, 0 cm to 10 cm); (2) secondary: Shoulder Pain and Disability Index (SPADI) disability subscale, quality of life on short-form (SF)-36 subscales, percent of patients who achieved at least a 30% decrease or a 2-point reduction in VAS pain (clinically meaningful pain relief), and safety. ⋯ The total number of adverse events was similar, which included 50 events in the BoNT/A group versus 46 events in the placebo group. A single injection of BoNT/A produced statistically significant and clinically meaningful pain relief and improvement in quality of life in patients with chronic refractory moderate/severe shoulder arthritis pain at 1 month. These data provide evidence to support the efficacy of this novel neurotoxin therapy that needs to be confirmed in a multicenter, randomized trial.
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The levels of circulating oxidized phospholipids (OxPLs) become increased in chronic and acute pathologic conditions such as hyperlipidemia, atherosclerosis, increased intimamedia thickness in the patients with systemic Lupus erythematosus, vascular balloon injury, acute lung injury (ALI), and acute respiratory distress syndrome (ARDS). These pathologies are associated with inflammation and activation of endothelial cells. ⋯ Recent reports show protective effects of OxPL in the models of endotoxin and ventilator-induced ALI and suggest a potential for using OxPL-derived cyclopenthenone-containing compounds with barrier-protective properties for drug design. These compounds may represent a new group of therapeutic agents for the treatment of lung syndromes associated with acute inflammation and lung vascular leak.
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Asbestos causes asbestosis (pulmonary fibrosis caused by asbestos inhalation) and malignancies (bronchogenic carcinoma and mesothelioma) by mechanisms that are not fully elucidated. Despite a dramatic reduction in asbestos use worldwide, asbestos-induced lung diseases remain a substantial health concern primarily because of the vast amounts of fibers that have been mined, processed, and used during the 20th century combined with the long latency period of up to 40 years between exposure and disease presentation. This review summarizes the important new epidemiologic and pathogenic information that has emerged over the past several years. ⋯ Furthermore, recent evidence underscores crucial roles for specific cellular signaling pathways that regulate the production of cytokines and growth factors. An evolving role for epithelial-mesenchymal transition (EMT) is also reviewed. The translational significance of these studies is evident in providing the molecular basis for developing novel therapeutic strategies for asbestos-related lung diseases and, importantly, other pulmonary diseases, such as interstitial pulmonary fibrosis and lung cancer.