Targeting p21-activated kinase 1 for development of a novel anti-arrhythmic drug class.

Evidence accumulated over the past decade suggests that p21-activated kinase 1 (PAK1) is a critical cardiac-protective signalling molecule. The present article provides an updated review of recent findings regarding the role of PAK1 in maintaining normal cardiac electrophysiological function through its regulation of membrane and Ca clocks. We first overviewed the PAK1 activation mechanism.

[The effect of emotional stressors on postoperative skin conductance indices: a prospective cohort pilot study].

Background: Skin conductance response reflects the activity of the sympathetic nervous system and is used to measure acute pain. This pilot study examines correlations of skin conductance response with emotional stressors postoperatively.

Methods: The correlation of skin conductance response with pain, anxiety, nausea and intellectual task performance was analyzed in postoperative patients.

A comparison of two different concentrations and infusion rates of ropivacaine in perineural infusion administered at the same total dose for analgesia after foot and ankle surgery: a randomized, double blinded, controlled study.

Background: Continuous popliteal nerve block is utilized for postoperative analgesia after foot and ankle surgery. Whether only the total dose of local anesthetic or the combination of concentration and volume determine the characteristics of a continuous popliteal nerve infusion remains currently unknown. We hypothesized a reduction of the incidence of insensate extremity in patients given ropivacaine 0.

Changes in the Skin Conductance Monitor as an End Point for Sympathetic Nerve Blocks.

Objective: There is a lack of objective methods for determining the achievement of sympathetic block. This study validates the skin conductance monitor (SCM) as an end point indicator of successful sympathetic blockade as compared with traditional monitors.

Methods: This interventional study included 13 patients undergoing 25 lumbar sympathetic blocks to compare time to indication of successful blockade between the SCM indices and traditional measures, clinically visible hyperemia, clinically visible engorgement of veins, subjective skin temperature difference, unilateral thermometry monitoring, bilateral comparative thermometry monitoring, and change in waveform amplitude in pulse oximetry plethysmography, within a 30-minute observation period.

Effect of sphingosine-1-phosphate on L-type calcium current and Ca(2+) transient in rat ventricular myocytes.

Modulation of Ca(2+) homoeostasis in cardiac myocytes plays a major role in beat-to-beat regulation of heart function. Previous studies suggest that sphingosine-1-phosphate (S1P), a biologically active sphingomyelin metabolite, regulates Ca(2+) handling in cardiac myocytes, but the underlying mechanism is unclear. In the present study, we tested the hypothesis that S1P-induced functional alteration of intracellular Ca(2+) handling includes the L-type calcium channel current (ICa,L) via a signalling pathway involving P21-activated kinase 1 (Pak1).

Lower-Dose Mepivacaine Plus Fentanyl May Improve Spinal Anesthesia for Knee Arthroscopy.

Background: Previous work indicates that 30 mg isobaric mepivacaine 1.5% plus 10 μg fentanyl produces reliable anesthesia for knee arthroscopy with a more rapid recovery profile than 45 mg mepivacaine.

Questions/purposes: This randomized controlled trial compared plain mepivacaine to three reduced doses of mepivacaine with 10 μg fentanyl for spinal anesthesia.

Risk Assessment for Chronic Pain and Patient Satisfaction After Total Knee Arthroplasty.

The estimated prevalence of patients who report minor or no improvement of their symptoms and pain after total knee arthroplasty (TKA) remains high, ranging from 5% to 40%. The authors sought to determine whether chronic pain and functional health are related to specific variations in demographic data, surgical techniques, or radiographic pre- and postoperative findings. They also sought to identify independent risk factors for persistent moderate-to-severe chronic pain after TKA.

The Impact of Hypotensive Epidural Anesthesia on Distal and Proximal Tissue Perfusion in Patients Undergoing Total Hip Arthroplasty.

Unlabelled: Little data exists to detail the effect of hypotensive epidural anesthesia on differential tissue oxygenation changes above and below the level of neuraxial blockade. This study was designed to investigate tissue oxygenation in a clinical setting, using non-invasive near-infrared spectroscopy.

Methods: Patients aged 18 to 85 years scheduled to undergo primary total hip arthroplasty were enrolled.

Association of obesity with inflammation and pain after total hip arthroplasty.

Background: The prevalence of obesity is increasing, and obesity often leads to degenerative joint disease requiring total hip arthroplasty (THA). Obesity is a proinflammatory state associated with an increase in chronic, low-grade inflammatory response. As such, it may augment the postoperative inflammatory response, which has been associated with postoperative pain and complications.

Predictors for moderate to severe acute postoperative pain after total hip and knee replacement.

Purpose: The ability to identify and focus care to patients at higher risk of moderate to severe postoperative pain should improve analgesia and patient satisfaction, and may affect reimbursement. We undertook this multi-centre cross-sectional study to identify preoperative risk factors for moderate to severe pain after total hip (THR) and knee (TKR) replacement.

Methods: A total of 897 patients were identified from electronic medical records.

A cross-sectional survey on prevalence and risk factors for persistent postsurgical pain 1 year after total hip and knee replacement.

Background And Objectives: There is a paucity of large multi-institutional surveys to determine the prevalence of and risk factors for persistent pain after total hip (THR) and knee (TKR) replacements. We surveyed a variety of practices and patients and also correlated persistent pain with health-related quality-of-life outcomes.

Methods: From October 10, 2007, to March 15, 2010, patients who had undergone primary THR or TKR with a minimum follow-up of 1 year were identified.

Association of perioperative use of nonsteroidal anti-inflammatory drugs with postoperative myocardial infarction after total joint replacement.

Background And Objectives: Use of nonsteroidal anti-inflammatory drug (NSAIDs) analgesics is controversial because of cardiovascular risk, but perioperative use may be advantageous for total joint replacement. Thus, we performed this single-center observational cohort study to determine any association between NSAID use and postoperative myocardial infarction (POMI).

Methods: All patient admissions undergoing total hip or knee replacement between March 3, 2009, and September 1, 2010, were identified.

A prospective survey of patient-controlled epidural analgesia with bupivacaine and clonidine after total hip replacement: a pre- and postchange comparison with bupivacaine and hydromorphone in 1,000 patients.

Background And Objectives: Patient-controlled epidural analgesia (PCEA) with bupivacaine and hydromorphone provides high quality analgesia after orthopedic surgery but is associated with a frequent incidence of opioid-related side effects (15%-30%). Epidural clonidine has a different side effect profile, but there are no large surveys documenting its use. We performed this prospective survey to evaluate analgesia and the side effect profile in total hip replacement patients before and after a systematic change from PCEA with bupivacaine/hydromorphone to bupivacaine/clonidine.

Increased transforming growth factor-β1 modulates glutamate receptor expression in the hippocampus.

Transforming growth factor-beta 1 (TGF-β1) is an inflammation-related cytokine. Its expression in the brain increases under conditions of neurodegenerative diseases and injuries. Previous studies have shown that genomic alterations of TGF-β1 expression in the brain cause neurodegenerative changes in aged mice.