Articles: function.
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Journal of neurotrauma · Jul 2014
PEG-PDLLA micelles treatment improves axonal function of the corpus callosum following traumatic brain injury.
The initial pathological changes of diffuse axonal injury following traumatic brain injury (TBI) include membrane disruption and loss of ionic homeostasis, which further lead to dysfunction of axonal conduction and axon disconnection. Resealing the axolemma is therefore a potential therapeutic strategy for the early treatment of TBI. Monomethoxy poly (ethylene glycol)-poly (D, L-lactic acid) di-block copolymer micelles (mPEG-PDLLA) have been shown to restore depressed compound action potentials (CAPs) of spinal axons and promote functional recovery after spinal cord injury. ⋯ Injection of fluorescent dye-labeled micelles revealed high fluorescent staining in cortical gray and white matters underneath the impact site. Labeling membrane-perforated neurons by injecting a membrane impermeable dye Texas Red-labeled dextran into lateral ventricles at 2 h post-CCI revealed that immediate micelle injection after CCI did not reduce the number of dye-stained cortical neurons and dentate granule cells of the hippocampus, indicating its ineffectiveness in repairing plasma membrane of neuronal somata. We conclude that intravenous administration of mPEG-PDLLA micelles immediately or at 4 h after TBI allows brain penetration via the compromised blood brain-barrier, and thereby improves the function of both myelinated and unmyelinated axons of the corpus callosum.
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Anesthesia and analgesia · Jul 2014
Randomized Controlled TrialA Novel Blood-Sparing Agent in Cardiac Surgery? First In-Patient Experience with the Synthetic Serine Protease Inhibitor MDCO-2010: A Phase II, Randomized, Double-Blind, Placebo-Controlled Study in Patients Undergoing Coronary Artery Bypass Grafting with Cardiopulmonary Bypass.
Antifibrinolytics have been used for 2 decades to reduce bleeding in cardiac surgery. MDCO-2010 is a novel, synthetic, serine protease inhibitor. We describe the first experience with this drug in patients. ⋯ This first-in-patient study demonstrated dosage-proportional PK for MDCO-2010 and reduction of chest tube drainage and transfusions in patients undergoing primary coronary artery bypass grafting. Antifibrinolytic and anticoagulant effects were demonstrated using various markers of coagulation. MDCO-2010 was well tolerated and showed an acceptable initial safety profile. Larger multi-institutional studies are warranted to further investigate the safety and efficacy of this compound.
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Reg Anesth Pain Med · Jul 2014
Ultrasound-Guided Injection of the Intrapelvic Portion of the Obturator Internus in a Cadaver Model.
Musculoskeletal dysfunction of the pelvic floor is common. One of the intrapelvic muscles, the obturator internus (OI), can be substantially stressed during its sharply angulated exit from the pelvis. However, there may be considerable overlap between symptoms and signs arising from the OI and other potential pain generators including the levator ani in the pelvic region. Accurate diagnosis for the OI might permit more efficient treatment combined with OI-specific exercise and behavior modification. Therefore, we hypothesized that ultrasound (US)-guided needle insertion in the intrapelvic portion of the OI would be accurate when a pararectal approach is used for diagnostic and therapeutic purposes. ⋯ The newly developed US-guided pararectal approach allowed accurate insertion of a needle into the intrapelvic portion of the OI. This US-guided method facilitated a more precise approach to the intrapelvic portion of the OI and may help differentiate conditions or symptoms caused by other structures.
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Variability in labor pain has been associated with demographic, clinical, and psychological factors. Polymorphisms of the β2-adrenergic receptor gene (ADRB2) influence sensitivity to experimental pain in humans and are a risk factor for chronic pain. The authors hypothesized that polymorphisms in ADRB2 may influence labor pain. ⋯ ADRB2 genotype correlates with labor pain but explained less than 1% of the intersubject variance in the model.
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Multicenter Study
Effects of Ivacaftor in cystic fibrosis patients carrying the G551D mutation with severe lung disease.
The development of ivacaftor represents a significant advance in therapeutics for patients with cystic fibrosis (CF) who carry the G551D mutation. Patients with an FEV1 < 40% predicted represent a considerable proportion of eligible patients but were excluded from phase 3 clinical trials, and the effectiveness of the drug in this population is, therefore, unknown. ⋯ Ivacaftor was clinically effective in patients with CF who carry the G551D mutation and have severe pulmonary disease. The reductions in treatment requirements were clinically and statistically significant and have not been described in less severe populations.