Mild electrical stimulation with heat shock reduces inflammatory symptoms in the imiquimod-induced psoriasis mouse model.

Psoriasis is a chronic skin disease caused by immune disorder. The chronic skin inflammation involves inflammatory molecules that are released from T lymphocytes and keratinocytes. Therefore, developing an anti-inflammatory therapy that is suitable for long-term treatment is needed. Electrical stimulation induces biological responses by modulating intracellular signaling pathways. Our previous studies showed that the optimized combination treatment of mild electrical stimulation (MES, 0.1-millisecond; ms, 55-pulses per second; pps) and heat shock (HS, 42°C) modulates inflammatory symptoms of metabolic disorders and chronic kidney disease in mice models and clinical trials. Here, we investigated the effect of MES+HS treatment on imiquimod-induced psoriasis mouse model. Topical application of imiquimod cream (15 mg) to mice ear induced keratinocyte hyperproliferation and psoriasis-like inflammation. In MES+HS-treated mice, imiquimod-induced skin hyperplasia was significantly decreased. MES+HS treatment reduced the protein expression of IL-17A and the infiltration of CD3-positive cells in lesioned skin. In addition, MES+HS-treated mice had decreased mRNA expression level of antimicrobial molecules (S100A8 and Reg3γ) which aggravate psoriasis. In IL-17A-stimulated HaCaT cells, MES+HS treatment significantly lowered the mRNA expression of aggravation markers (S100A8, S100A9 and ß-defensin2). Taken together, our study suggested that MES+HS treatment improves the pathology of psoriasis via decreasing the expression of inflammatory molecules.

GABA(B) receptors do not internalize after baclofen treatment, possibly due to a lack of ß-arrestin association: study with a real-time visualizing assay.

The mechanism of agonist-induced GABA(B) receptor (GABA(B) R) internalization is not well understood. To investigate this process, we focused on the interaction of GABA(B) R with ß-arrestins, which are key proteins in the internalization of most of the G protein-coupled receptors, and the agonist-induced GABA(B) R internalization and the interaction of GABA(B) R with ß-arrestin1 and ß-arrestin2 were investigated in real time using GABA(B) R and ß-arrestins both of which were fluorescent protein-tagged. We then compared these profiles with those of µ-opioid receptors (µOR), well-studied receptors that associate and cointernalize with ß-arrestins. When stimulated by the specific GABA(B) R agonist baclofen, GABA(B) R composed of GABA(B1a) R (GB(1a) R) and fluorescent protein-tagged GABA(B2) R-Venus (GB2 R-V) formed functional GABA(B) R; they elicited G protein-activated inwardly rectifying potassium channels as well as nontagged GABA(B) R. In cells coexpressing GB(1a) R, GB2 R-V, and ß-arrestin1-Cerulean (ßarr1-C) or ß-arrestin2-Cerulean (ßarr2-C), real-time imaging studies showed that baclofen treatment neither internalized GB2 R-V nor mobilized ßarr1-C or ßarr2-C to the cell surface. This happened regardless of the presence of G protein-coupled receptor kinase 4 (GRK4), which forms a complex with GABA(B) R and causes GABA(B) R desensitization. On the other hand, in cells coexpressing µOR-Venus, GRK2, and ßarr1-C or ßarr2-C, the µOR molecule formed µOR/ßarr1 or µOR/ßarr2 complexes on the cell surface, which were then internalized into the cytoplasm in a time-dependent manner. Fluorescence resonance energy transfer assay also indicated scarce association of GB2 R-V and ß-arrestins-C with or without the stimulation of baclofen, while robust association of µOR-V with ß-arrestins-C was detected after µOR activation. These findings suggest that GABA(B) Rs failure to undergo agonist-induced internalization results in part from its failure to interact with ß-arrestins.

S(+)-ketamine suppresses desensitization of γ-aminobutyric acid type B receptor-mediated signaling by inhibition of the interaction of γ-aminobutyric acid type B receptors with G protein-coupled receptor kinase 4 or 5.

BACKGROUND: Intrathecal baclofen therapy is an established treatment for severe spasticity. However, long-term management occasionally results in the development of tolerance. One of the mechanisms of tolerance is desensitization of γ-aminobutyric acid type B receptor (GABABR) because of the complex formation of the GABAB2 subunit (GB2R) and G protein-coupled receptor kinase (GRK) 4 or 5. The current study focused on S(+)-ketamine, which reduces the development of morphine tolerance. This study was designed to investigate whether S(+)-ketamine affects the GABABR desensitization processes by baclofen. METHODS: The G protein-activated inwardly rectifying K channel currents induced by baclofen were recorded using Xenopus oocytes coexpressing G protein-activated inwardly rectifying K channel 1/2, GABAB1a receptor subunit, GB2R, and GRK. Translocation of GRKs 4 and 5 and protein complex formation of GB2R with GRKs were analyzed by confocal microscopy and fluorescence resonance energy transfer analysis in baby hamster kidney cells coexpressing GABAB1a receptor subunit, fluorescent protein-tagged GB2R, and GRKs. The formation of protein complexes of GB2R with GRKs was also determined by coimmunoprecipitation and Western blot analysis. RESULTS: Desensitization of GABABR-mediated signaling was suppressed by S(+)-ketamine in a concentration-dependent manner in the electrophysiologic assay. Confocal microscopy revealed that S(+)-ketamine inhibited translocation of GRKs 4 and 5 to the plasma membranes and protein complex formation of GB2R with the GRKs. Western blot analysis also showed that S(+)-ketamine inhibited the protein complex formation of GB2R with the GRKs. CONCLUSION: S(+)-Ketamine suppressed the desensitization of GABABR-mediated signaling at least in part through inhibition of formation of protein complexes of GB2R with GRK 4 or 5.

Usefulness of immature platelet fraction for the clinical evaluation of myelodysplastic syndromes.

Ratios of young platelets or reticulated platelets can be routinely obtained as an immature platelet fraction (IPF) with the XE-2100 automated hematology analyzer (Sysmex, Kobe, Japan). We combined IPF analysis of 31 patients with myelodysplastic syndrome (MDS) with a complete blood count, a bone marrow examination, and a chromosome analysis. The patients with >40 x 10(9)/L platelets were classified as group A, and those with > or =40 x 10(9)/L were placed in group B. The 2 groups were subclassified as A1 or B1 for patients with an IPF of <10% and as A2 or B2 for those with an IPF > or =10%. Categories A1, A2, B1, and B2 comprised 12 patients, 6 patients, 7 patients, and 6 patients, respectively. Patients with a relatively high IPF (>10%) (category A2 or B2) showed distinctive characteristics. Group B2 showed a higher frequency of chromosomal abnormalities than B1 (P = .029), and group A2 tended to show a higher incidence of clinical improvement than A1 (P = .08). IPF determination may be clinically useful for the assessment of prognosis for MDS patients.

Postoperative analgesic effect of preoperative intravenous flurbiprofen in arthroscopic rotator cuff repair.

PURPOSE: This study was carried out to evaluate the postoperative analgesic effects of preoperative intravenous flurbiprofen in patients undergoing arthroscopic rotator cuff repair under general anesthesia. METHODS: We studied 44 patients who underwent an elective arthroscopic rotator cuff repair in a prospective, randomized, and double-blind fashion. The patients were divided into two groups. Group A (n = 22) received lipid emulsion 0.1 ml kg(-1) as a placebo, and group B (n = 22) received flurbiprofen 1 mg kg(-1) before the surgery. Intralipid or flurbiprofen was given intravenously 5 min before the surgery. General anesthesia was maintained with sevoflurane and nitrous oxide, and 10 ml of 0.75% ropivacaine was administered intraarticularly at the end of the surgery. Postoperative analgesia was supplied with intravenous 0.1 mg buprenorphine according to the patient's demand. The effectiveness of flurbiprofen's analgesic effect was measured by a visual analog scale (VAS) and by the amount of buprenorphine consumption at 0.5, 1, 2, 4, 6, 12, and 24 h after the surgery. Time to the first analgesic was also recorded. RESULTS: VAS in group B was significantly (P < 0.01) lower than that in group A during the first 6 h postoperatively. The amount of buprenorphine consumption in group B was also significantly (P < 0.01) less than that in group A within the first 2 h postoperatively. The time to first analgesic request in group B was significantly (P < 0.01) longer than that in group A. CONCLUSION: These results show that preoperative intravenous flurbiprofen facilitates the analgesic effect in the early postoperative period after arthroscopic rotator cuff repair.

Age-dependent relationship between bispectral index and sedation level.

STUDY OBJECTIVE: To determine the relationship between bispectral index (BIS) and sedation. DESIGN: Prospective, observational clinical study. SETTING: Intensive care unit of a public hospital in Japan. PATIENTS: 22 ASA physical status I, II, and III middle-aged (18-65 yrs) and elderly (>65 yrs) patients receiving postoperative sedation with midazolam. INTERVENTIONS: Patients were allocated to two groups: Group M was composed of middle-aged patients (<65 yrs) and Group H elderly patients (>65 yrs). Midazolam was administered at a bolus dose of 0.1 mg/kg, followed by a continuous dose of 0.04 mg/kg per hour, which was adjusted every two hours to achieve a target level of sedation at 3-6 on the Ramsay Sedation Scale (RSS); buprenorphine was administered at a constant rate (0.625 microg kg(-1) hr(-1)). MEASUREMENTS: BIS value, RSS, midazolam dose, body temperature (BT), heart rate, dopamine dose, and mean arterial pressure were recorded every two hours by an independent nurse. Data were analyzed using Spearman rank correlation and the Mann-Whitney U test. MAIN RESULTS: BIS values decreased depending on depth of sedation; a significant correlation was noted between groups in RSS and BIS. The BIS values at levels of RSS 5 and 6 were significantly lower in Group H than Group M. CONCLUSION: BIS correlated with sedation depth, with BIS scores in group H than group M at a deep sedation depth.

[Change of sedation depth, oxygen consumption index and hemodynamics after withdrawal of midazolam sedation].

BACKGROUND: The change of oxygen consumption after withdrawal of sedation is controversial. We evaluated the changes of sedation depth, oxygen consumption and hemodynamics after withdrawal of midazolam sedation in the patients undergoing major abdominal surgery. METHODS: We evaluated 18 patients after major abdominal surgery. Midazolam was used for intravenous sedation after admission to the ICU. Midazolam was administered at a bolus dose of 0.1 mg kg(-1), followed by continuous infusion at 0.04 mg kg(-1) hr(-1), which was adjusted every 2 hrs to achieve a desired level of sedation of 4 on Ramsay sedation scale (RSS). After about 14 hours of sedation, we stopped the infusion of midazolam. From that time, we measured systolic and mean arterial pressure, heart rate, minute volume and oxygen consumption, and evaluated RSS every 5 minutes for 1 hour. We evaluated RSS as sedation depth, oxygen consumption index (V(O2)I) and rate pressure product (RPP=systolic arterial pressure x heart rate) as hemodynamic parameters. RESULTS: RSS significantly decreased gradually, but the other parameters including V(O2)I and RPP were unchanged. CONCLUSIONS: After withdrawal of midazolam sedation in the patients undergoing major abdominal surgery, the sedation depth became lighter, but V(O2)I and RPP were unchanged.

Theophylline-bearing microspheres with dual features as a coordinative adsorbent and catalytic support for palladium ions.

Polystyrenic microspheres in the sub 5 micrometer size range (micro-gel) with -CH2Cl active sites were synthesized via the dispersion polymerization of 4-chloromethylstyrene, divinyl benzene and methoxy polyethylene glycol acrylate. Then, theophylline residues were introduced onto the polystyrenic microspheres via the substitution of the chloride in the -CH2Cl group to prepare chelate type microspheres of µ-T2. It was found that the microspheres have co-continuous structures, monodispersed particle sizes, and excellent solvent and water wettability. Using the µ-T2 microspheres possessing theophylline residues, adsorption experiments involving the adsorption of palladium(ii), copper(ii) and platinum(iv) from acidic chloride media under both individual and mixed conditions were carried out and it was found that the µ-T2 microspheres exhibited excellent adsorption selectivity for palladium(ii) over copper(ii) and platinum(iv). It was also revealed that thiourea or ammonia solutions are the most effective in desorbing palladium ions from the microspheres. Despite being used in four adsorption-desorption cycles, the µ-T2 microspheres were still able to strongly adsorb palladium ions, with an adsorption of over 85%. In addition, the µ-T2 microspheres also showed palladium capturing ability even in very dilute palladium solutions (below 1.0 ppm). Interestingly, the µ-T2 microsphere-adsorbed palladium ions exhibited excellent catalytic activity in the Suzuki-Miyaura coupling reaction of bromobenzene and phenylboronic acid, yielding biphenyl in 100% under the conditions within 1 hour at 50 °C in water.

Microalbuminuria is a prognostic predictor in aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To determine the prevalence and the prognostic significance of microalbuminuria in patients after aneurysmal subarachnoid hemorrhage (SAH). DESIGN: Prospective and observational clinical study. SETTING: Multidisciplinary intensive care unit. PATIENTS: Fifty-one consecutive patients who underwent aneurysm clipping or endovascular surgery after SAH; 8 patients who underwent surgical clipping for unruptured intracerebral aneurysm served as control. INTERVENTION: None. MEASUREMENTS AND RESULTS: General clinical and neurological data were recorded on admission. Urine was collected preoperatively and daily for up to 7 days postoperatively for measuring the urinary microalbumin/creatinine ratio. The Glasgow Coma Scale (GCS) score was also determined on admission and daily for up to 7 days after operation. Neurological outcome was assessed using the Glasgow Outcome Scale (GOS) at 3 months after stroke. The prevalence rates of microalbuminuria were 74.5% in SAH and 37.5% in the control. Among the 51 patients, 25 had unfavorable neurological outcome (GOS 1-3). The areas under the receiver operator characteristic curves showed that the highest urinary microalbumin/creatinine ratio and the lowest GCS score during the first 8 days were the significant predictors of unfavorable neurological outcome. The threshold value, sensitivity, specificity, and likelihood ratio for the highest urinary microalbumin/creatinine ratio were 200 mg/g, 60% [95% confidence interval (CI) 41-79], 96% (95% CI 88-100), and 15.6 (95% CI 9.1-26.7), respectively. CONCLUSIONS: This study confirms a high prevalence of microalbuminuria in the SAH patients, and it suggests that the highest urinary microalbumin/creatinine ratio > 200 mg/g during the first 8 days is a significant predictor of unfavorable neurological outcome.

Preadministration of flurbiprofen suppresses prostaglandin production and postoperative pain in orthopedic patients undergoing tourniquet inflation.

STUDY OBJECTIVES: To evaluate the effect of preadministration of flurbiprofen on the plasma concentrations of prostaglandin E2 (PGE2) and postoperative pain. DESIGN: Prospective, randomized, controlled and double-blind study. SETTING: Inpatient surgery at Nagasaki Rosai Hospital. PATIENTS: 32 ASA physical status I to II patients scheduled for total knee arthroplasty or open anterior cruciate ligament reconstruction. INTERVENTIONS: Patients were randomly assigned to two groups. Five minutes before tourniquet inflation (350 mmHg), group A (n = 16) received placebo (intralipid, one mL . kg(-1)), and group B (n = 16) received flurbiprofen one mg . kg(-1) IV. Catheters were placed in the ipsilateral femoral vein for collection of local blood and in a cubital vein for sampling of systemic blood. MEASUREMENTS: Prostaglandin E2 (femoral vein and cubital vein) was measured before tourniquet inflation (T1), before tourniquet deflation (T2), and immediately after tourniquet deflation (T3). Postoperative analgesia was provided with intravenous buprenorphine, 0.1 mg, on patient demand. Pain (Visual Analog Scale) was assessed at 0.5, one, two, 4, 6, 12 and 24 hours after surgery. MAIN RESULTS: Visual Analog Scale and buprenorphine consumptions in group B were significantly lower than those in group A during the first 4 postoperative hours. In group A, PGE2 in femoral vein increased significantly at T2 (359 +/- 105 pg mL(-1), P < 0.0001), compared with T1 (211 +/- 61 pg mL(-1)) and returned to control values at T3 (252 +/- 77 pg mL(-1)), whereas PGE2 in the cubital vein showed no change. In group B, PGE2 in either the femoral vein or cubital vein showed no change throughout the time course. CONCLUSIONS: Preadministration of flurbiprofen suppresses the local production of PGE2 during tourniquet ischemia, resulting in reduced early postoperative pain in patients undergoing knee surgery.

Human middle cerebral artery flow velocity during controlled hypotension combined with hemodilution-transcranial Doppler study.

STUDY OBJECTIVE: To evaluate the effects of controlled hypotension combined with hemodilution on human middle cerebral artery flow velocity (Vmca) by transcranial Doppler ultrasonography. DESIGN: Randomized prospective study. SETTING: Inpatient surgery at Nagasaki Rosai Hospital. PATIENTS: Thirty American Society of Anesthesiologists physical status I and II patients scheduled for total hip arthroplasty. INTERVENTIONS: Anesthesia was maintained with nitrous oxide-oxygen (N(2)O-O(2)) and sevoflurane during normocapnia. Hemodilution was carried out after induction of anesthesia, in which blood was withdrawn then replaced with the same amount of hydroxyethyl starch to achieve a final hematocrit level of 32% (group A = mild hemodilution group, N = 15) or 24% (group B = moderate hemodilution group, N = 15). In both groups, controlled hypotension was induced with prostaglandin E(1) to maintain mean arterial pressure at approximately 55 mm Hg for 80 minutes. MEASUREMENTS AND MAIN RESULTS: Vmca and blood gas were measured before hemodilution, after hemodilution, 80 minutes after starting hypotension, and 60 minutes after recovery from hypotension. Vmca significantly increased in group A (+122%) and group B (+156%) after each hemodilution. In group B, Vmca was significantly greater than baseline values at 80 minutes after starting hypotension (+135%) and 60 minutes after recovery from hypotension (+140%). CONCLUSION: The combination of moderate hemodilution, such as hematocrit value of 24%, and prostaglandin E(1)-induced hypotension would not impair middle cerebral artery flow during sevoflurane-N(2)O-O(2) anesthesia during normocapnia.

[Management of postoperative pharyngeal swelling after anterio-posterior cervical fusion under pharyngoscopy].

A 47-year-old man with traumatic cervical spinal cord injury underwent anterio-posterior cervical fusion, which accompanied high-risk of upper airway obstruction by postoperative reactive pharyngeal swelling. After the operation, we ascertained that he had no paralysis of his extremities, and sedation and mechanical ventilation were started at ICU. We evaluated the degree of edema in the hypopharyngeal and supraglottic regions with pharyngoscopy. On postoperative day 3, the direct fiberoptic evaluation showed postoperative swelling of the upper airway. On postoperative day 8, extubation was performed after confirming the healing pharyngeal edema by fibroptic evaluation. To achieve successful extubation, fibroptic pharyngoscopy should show that the pharynx around the endotracheal tube wide enough to see the larynx including epiglottis. Pharyngoscopy is a useful method to evaluate the upper airway.

Increased incidence of emergency airway management after combined anterior-posterior cervical spine surgery.

Among some kinds of cervical spine surgeries, combined anterior-posterior cervical spine surgery (CAP-CS surgery) requires prolonged operative time and highly invasive procedure. This study was performed to determine whether CAP-CS surgery was associated with increased risk of emergency airway management compared with other cervical spine surgeries (O-CS surgeries). The records of the patients who underwent cervical spine surgery between July 2001 and March 2003 at our institution were reviewed retrospectively, and we determined whether the CAP-CS surgery was associated with an increased risk of emergency airway management in comparison with O-CS surgeries, using the logistic regression analysis. A total of 165 were eligible for inclusion in the study. A total of 127, 20, 11, 5, and 2 patients suffered from cervical myelopathy, traumatic cervical spinal cord injury, atlantoaxial dislocation, cervical spinal tumors, and cervical pyogenic spondylitis, respectively. The operative approaches were CAP-CS surgery, anterior surgery, posterior surgery, and atlantoaxial surgery in 10, 56, 88, and 11 patients, respectively. Thus, the operative approaches were CAP-CS surgery in 10 patients and O-CS surgeries in 155 patients. Postoperative emergency airway management was required in 7 of the 10 patients (70%) who underwent CAP-CS surgery, and 2 of the 155 patients (1%) who underwent O-CS surgeries. The increased risk of postoperative emergency airway management imposed by CAP-CS surgery was 178.5 by an odds ratio, with a 95% confidence interval of 25.6 to 1246. The results show that CAP-CS surgery provides a major risk factor for postoperative emergency airway management.

Prostaglandin E1 but not corticosteroid increases nerve root blood flow velocity after lumbar diskectomy in surgical patients.

The purpose of this study was to clarify whether prostaglandin E1 (PGE(1)) or corticosteroid could increase blood flow in the nerve root because neurologic symptoms in spinal stenosis may be based on the vascular insufficiency in the nerve root. Fifty-seven patients undergoing lumbar diskectomy were randomly assigned to one of three groups. Each group received one of three protocols for intravenous injection: 10 mL of saline solution, group A (n = 19); 10 mL of PGE(1) (20 microg) solution, group B (n = 19); and 10 mL of dexamethasone (8 mg) solution, group C (n = 19). After lumbar diskectomy, a probe for laser Doppler flowmetry was placed directly on the lumbar nerve root. Nerve root blood flow (RBF) velocity and mean arterial pressure (MAP) were measured before injection (T0), 5 minutes after the start of injection (T1), 10 minutes after the start of injection (T2), and 10 minutes after the end of injection (T3). In groups A and C, these did not change throughout the time course. In group B, MAP decreased significantly at T1 (92%; P <.001), T2 (89%; P <.0001), and T3 (91%; P <.0001), while RBF velocity increased significantly at T1 (125%; P <.05), T2 (128%; P <.05), and T3 (121%; P <.05) compared with T0. The values in group B were different from those in group A (P <.05) and group C (P <.05) at T1 and T2. The results show that intravenous injection of low-dose PGE(1), but not corticosteroid, increases RBF velocity after lumbar diskectomy.

[A case of acute respiratory distress syndrome (ARDS) caused by splenic infarction].

Acute respiratory distress syndrome (ARDS) is the most severe lung injury caused by many pathologic states. We treated a patient who suffered from ARDS caused by splenic infarction. A 75-year-old patient had a gastric cancer with multiple lung and liver metastasis. During anti-cancer therapy, she developed a high fever (above 39 degrees C) and a chest and an abdominal CT scan revealed splenic infarction. Hypoxia progressed gradually and she was transferred to ICU with tracheal intubation. Mechanical ventilation was performed according to open lung strategy, but she did not recover. On ICU day 3, the bilateral infiltration shadow on her chest X-ray was pointed out, and she had a low central venous pressure. We diagnosed her ARDS. The administration of methylprednisolone was started according to Meduri's report. Hypoxia was improved gradually and on ICU day 7, she was weaned from mechanical ventilation, and extubated. On ICU day 8, she was returned to her ward without ventilatory support.

Influence of low-molecular-weight hydroxyethyl starch on microvascular permeability in patients undergoing abdominal surgery: comparison with crystalloid.

PURPOSE: Adequate volume therapy is essential for stable hemodynamics and sufficient urinary output perioperatively. Hydroxyethyl starch (HES) has been reported to attenuate the microvascular hyperpermeability which occasionally occurs in surgical patients. This study was carried out to evaluate the effect of low-molecular-weight HES on the urinary microalbumin/creatinine ratio (MACR), a marker of microvascular permeability, in surgical patients. METHODS: In a prospective, controlled, and randomized clinical trial, 21 patients undergoing abdominal surgery were divided into two groups. Group HES (n = 10) received HES at 2 ml x kg(-1) x h(-1) during surgery and at 1 ml x kg(-1) x h(-1) after surgery, and additionally they received acetated Ringer's solution (AR) at a rate to keep central venous pressure (CVP) 5 mm Hg. Group AR (n = 11) received AR at a rate to keep CVP at 3-5 mmHg. MACR, soluble intercellular adhesion molecule-1 (sICAM-1), and urinary output were measured intermittently in the perioperative period. RESULTS: MACR was significantly increased during surgery in both groups. There was no significant difference in MACR between the two groups throughout the study period. The serum concentration of sICAM-1 decreased during surgery in both groups, and that in group HES was significantly lower than that in group AR at the end of surgery. Postoperative urinary output in group HES was greater than that in group AR. The intensive care unit (ICU) stay in group HES was shorter than that in group AR. CONCLUSION: Although low-molecular-weight HES does not improve microvascular hyperpermeability, the expansion of the intravascular volume by HES results in higher urinary output in the postoperative period than that seen with crystalloid solution. The lower concentration of sICAM-1 after surgery may be due to hemodilution.

Comparison of oxygen consumption calculated by Fick's principle (using a central venous catheter) and measured by indirect calorimetry.

We investigated the clinical usefulness of the Fick method using central venous oxygen saturation ScvO2 and cardiac output (CO) measured by pulse dye densitometry (PDD) for monitoring oxygen consumption VO2. This prospective clinical study was performed in 28 mechanically ventilated postoperative patients after major abdominal surgery. VO2 was determined by two methods, i.e., the Fick method and indirect calorimetry. The Fick method was employed using CO measured by PDD and VO2 obtained from a central venous catheter (CVC). VO2 measured by indirect calorimetry was averaged for 15 min. Fifty-six sets of measurements were performed. VO2 values determined by the Fick method were significantly lower than those measured by indirect calorimetry (110 +/- 29 vs 148 +/- 28 ml x min(-1) x m(-2); P < 0.01). Bland and Altma analysis showed that the mean bias and precision were 33 ml x min(-1) x m(-2) and 32 ml x min(-1) x m(-2), respectively. The correlation between the two measurements of VO2 was weak (r (2) = 0.145; P = 0.0038), indicating that the Fick method using PDD and ScvO2 is not clinically acceptable for the monitoring of VO2.

Adhesiolysis and targeted steroid/local anesthetic injection during epiduroscopy alleviates pain and reduces sensory nerve dysfunction in patients with chronic sciatica.

PURPOSE: The aim of this study was to evaluate the effect of adhesiolysis followed by the injection of steroid and local anesthetic during epiduroscopy on sensory nerve function, pain, and functional disability in patients with chronic sciatica. METHODS: Epidural adhesiolysis, using epiduroscopy, followed by the injection of steroid and local anesthetic, was scheduled in 19 patients with chronic sciatica refractory to lumbar epidural block. Sensory nerve function in the legs was tested with a series of 2000-Hz (Abeta-fiber), 250-Hz (Adelta-fiber), and 5-Hz (C-fiber) stimuli, using the current perception threshold (CPT), and CPT values and intensity of pain and Roland Morris Disability Questionnaire (RMDQ) scores were assessed before and 1 and 3 months after the epiduroscopy. RESULTS: At all frequencies, the CPT values in the affected legs of patients before the epiduroscopy were significantly higher than those in the unaffected legs. Epidural adhesiolysis was successfully performed in 16 of the 19 patients. In these patients, the CPT values at 2000 and 250 Hz, and the pain and RMDQ scores 1 and 3 months after the epiduroscopy were significantly lower than those before the epiduroscopy, while the CPT value at 5 Hz did change. CONCLUSION: Epidural adhesiolysis followed by the injection of steroid and local anesthetic during epiduroscopy alleviated pain, and functional disability, and reduced dysfunction of Abeta and Adelta fibers in patients with chronic sciatica.

mu-Opioid receptor forms a functional heterodimer with cannabinoid CB1 receptor: electrophysiological and FRET assay analysis.

Interactions between mu-opioid receptor (muOR) and cannabinoid CB1 receptor (CB1R) were examined by morphological and electrophysiological methods. In baby hamster kidney (BHK) cells coexpressing muOR fused to the yellow fluorescent protein Venus and CB1R fused to the cyan fluorescent protein Cerulean, both colors were detected on the cell surface; and fluorescence resonance energy transfer (FRET) analysis revealed that muOR and CB1R formed a heterodimer. Coimmunoprecipitation and Western blotting analyses also confirmed the heterodimers of muOR and CB1R. [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) or CP55,940 elicited K+ currents in Xenopus oocytes expressing muOR or CB1R together with G protein activated-inwardly rectifying K+ channels (GIRKs), respectively. In oocytes coexpressing both receptors, either of which was fused to the chimeric Galpha protein Gqi5 that activates the phospholipase C pathway, both DAMGO and CP55,940 elicited Ca2+-activated Cl(-) currents, indicating that each agonist can induce responses through Gqi5 fused to either its own receptor or the other. Experiments with endogenous Gi/o protein inactivation by pertussis toxin (PTX) supported the functional heterodimerization of muOR/CB1R through PTX-insensitive Gqi5(m) fused to each receptor. Thus, muOR and CB1R form a heterodimer and transmit a signal through a common G protein. Our electrophysiological method could be useful for determination of signals mediated through heterodimerized G protein-coupled receptors.

Preadministration of low-dose ketamine reduces tourniquet pain in healthy volunteers.

We evaluated whether preadministration of low-dose ketamine could attenuate tourniquet pain and arterial pressure increase using high tourniquet pressure in ten healthy awake volunteers. Ketamine, 0.1 mg x kg(-1), or normal saline was given intravenously in a double-blind fashion before tourniquet inflation with a pressure of 400 mmHg at the thigh. Visual analog scale (VAS) scores and systolic blood pressure (SBP) were measured at 5-min intervals. Ketamine significantly reduced VAS scores compared to saline just after tourniquet inflation [90 (64-100) mm, median (range), with saline versus 66 (50-81) mm with ketamine, P < 0.01] and at 30 min [92 (61-100) mm with saline versus 70 (50-100) mm with ketamine, P < 0.03), and significantly prolonged tourniquet time (28 +/- 6 min with saline, mean +/- SD, versus 37 +/- 7 min with ketamine, P < 0.01). SBP (120 +/- 9 mmHg) significantly increased before tourniquet deflation (133 +/- 16 mmHg) in the saline trial, but not in the ketamine trial. The results show that preadministration of low-dose ketamine attenuates tourniquet pain and arterial pressure increase during high-pressure tourniquet application and prolongs tourniquet time in healthy volunteers.