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Background The lumbar sympathetic ganglion block (LSGB) has been used as a diagnostic and therapeutic procedure for treating pain conditions such as neuropathic and ischemia-related pain, affecting the lower extremities. In general, an increase in skin temperature is useful in confirming the effectiveness of the sympathetic nerve block in clinical settings. However, the assessment of skin temperature in patients with peripheral arterial disease (PAD) occasionally provides false negatives. Case presentation A novel technology, laser speckle flowgraphy (LSFG) enables noninvasive quantitative and qualitative blood flow assessments. LSFG is a novel neuro-monitor for quantitative blood flow detection in the optic nerve head during cardiac surgery. Herein, we report on measuring foot blood flow using LSFG before and after LSGB in a PAD patient. This research aimed to determine whether LSFG could detect any improvement in the dynamics of foot blood flow after an LSGB in a situation where changes in skin temperature alone could not determine the procedure's outcome. Conclusion LSFG can be used to assess blood flow changes in a foot with PAD, following a LSGB.

Surgical revascularisation to accomplish limb salvage remains preferable in some patients with chronic limb threatening ischaemia (CLTI). The aim of this study was to evaluate the effectiveness and safety of ultrasound guided lower extremity nerve blockade (UGNB) in infragenicular bypass surgery (IGBS).This was a single centre, retrospective clinical study. Fifty-nine patients with CLTI (67 limbs) who underwent IGBS under UGNB (femoral and sciatic nerve blockade) at Asahikawa Medical University between January 2012 and December 2017 were compared with patients with CLTI (137 limbs) who underwent IGBS under general anaesthesia (GA) over the same period. Propensity score matching based on pre-operative comorbidities was used to minimise background differences of the two groups.Fifty-six pairs of CLTIs were matched and analysed (55% dialysis dependent). Procedure duration was similar between the two groups, but intraoperative catecholamine index and intravenous fluid volume were lower with UGNB compared with GA (2.9 ± 4.6 vs. 5.9 ± 6.5; p .01 and 1831 ± 990 vs. 2335 ± 931 mL; p .01, respectively). The mean arterial blood pressure during induction of anaesthesia was significantly decreased with GA. Post-operatively, the time period to resume a clear liquid and solid food diet was significantly shorter with UGNB (P0.01 for both outcome measures). Intravenous fluid volume was significanlty lower, while cardiac complications and delirium, based on the NEECHAM confusion scale, occurred significantly less often with UGNB than GA. These significant differences show advantages of UGNB compared to GA. No mortality or major amputations were observed in either group. Early graft thrombosis was observed in five limbs (8.9%) with UGNB and in four limbs with GA (7.1%) (p = .73).UGNB has advantages for intra- and post-operative management and could be a useful method to prevent peri-operative complications for high risk patients with CLTI. To ensure the effectiveness of UGNB for IGBS for future indications, a randomised study is required.

Objective This study aimed to compare measurements of right ventricular function using three-dimensional transesophageal echocardiography (3D TEE), and pulmonary artery catheters (PACs) in patients undergoing cardiac surgery. The authors examined the practicality of using the 3D TEE. Design Prospective observational. Setting Cardiac operating room at a single university hospital. Participants All adult patients undergoing elective cardiac surgery at a single tertiary care university hospital over two years. Interventions None. Measurements and Main Results Right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV), stroke volume (SV), and right ventricular ejection fraction (RVEF) were measured with both 3D TEE and PACs. Assessments were performed using correlation coefficients, paired t tests, and Bland-Altman plots. Thirty-one patients participated in this study. Each measurement showed good agreement. RVEDV and RVESV were slightly lower on 3D TEE than on PAC (205.9 mL v 220.2 mL, p = 0.0018; 143.0 mL v 155.5 mL, p = 0.0143, respectively), whereas no significant differences were observed for SV and RVEF (31.0% v 31.1%, p = 0.0569; 61.6 mL v 66.9 mL, p = 0.92, respectively). Linear regression analysis showed high correlation between 3D TEE and PAC for RVEDV (r = 0.87) and RVESV (r = 0.81), and moderate correlation for SV (r = 0.67) and RVEF (r = 0.67). In the Bland-Altman plot, most patients were within the 95% limits of the agreement throughout all measurements. Conclusion A high correlation was found between measurements made with a PAC and with 3D TEE in the assessment of right ventricular function. Three-dimensional TEE would be a potential alternative to PAC for assessment of right ventricular function during intraoperative periods.

BackgroundSeveral neuraxial techniques have demonstrated effective post-cesarean section analgesia. According to previous reports, it is likely that patient-controlled epidural analgesia (PCEA) without opioids is inferior to intrathecal morphine (IM) alone for post-cesarean section analgesia. However, little is known whether adding PCEA to IM is effective or not. The aim of this study was to compare post-cesarean section analgesia between IM with PCEA and IM alone.MethodsFifty patients undergoing elective cesarean section were enrolled in this prospective randomized study. Patients were randomized to one of two groups: IM group and IM + PCEA group. All patients received spinal anesthesia with 12 mg of 0.5% hyperbaric bupivacaine, 10 μg of fentanyl, and 150 μg of morphine. Patients in IM + PCEA group received epidural catheterization through Th11–12 or Th12-L1 before spinal anesthesia and PCEA (basal 0.167% levobupivacaine infusion rate of 6 mL/h, bolus dose of 3 mL in lockout interval of 30 min) was commenced at the end of surgery. A numerical rating scale (NRS) at rest and on movement at 4,8,12,24,48 h after the intrathecal administration of morphine were recorded. In addition, we recorded the incidence of delayed ambulation and the number of patients who requested rescue analgesics. We examined NRS using Bonferroni’s multiple comparison test following repeated measures analysis of variance;p was considered as statistically significant.ResultsTwenty-three patients in each group were finally analyzed. Mean NRS at rest was significantly higher in IM group than in IM + PCEA group at 4 (2.7 vs 0.6), 8 (2.2 vs 0.6), and 12 h (2.5 vs 0.7), and NRS during mobilization was significantly higher in IM group than in IM + PCEA group at 4 (4.9 vs 1.5), 8 (4.8 vs 1.9), 12 (4.9 vs 2), and 24 h (5.7 vs 3.5). The number of patients who required rescue analgesics during the first 24 h was significantly higher in IM group compared to IM + PCEA group. No significant difference was observed between the groups in incidence of delayed ambulation.ConclusionsThe combined use of PCEA with IM provided better post-cesarean section analgesia compared to IM alone.Trial registrationUMIN-CTR (Registration No.UMIN000032475). Registered 6 May 2018 – Retrospectively registered.

We compared the reversal doses of sugammadex in surgical cases in which intraoperative neuromuscular monitor were used, to cases in which intraoperative neuromuscular monitoring was not used, retrospectively.Data were collected by reviewing the electronic medical records of patients who received rocuronium and sugammadex during general anesthesia at Asahikawa Medical University Hospital between May 1, 2017 and April 30, 2018. The primary outcome was the reversal dose of sugammadex per patient actual body weight (mg/kg) between the group in which intraoperative neuromuscular monitoring was used (NM+ group) and the group in which intraoperative neuromuscular monitoring was not used (NM- group).A total of 3496 patients were evaluated, with 2544 patients (73%) included in NM+ group and 952 patients (27%) in NM- group. The reversal doses of sugammadex per actual body weight were significantly higher in NM- group compared to NM+ group. In the NM+ group, 521 patients (20%) received 2 mg/kg sugammadex, 1377 patients (54%) received 2 ~ 2.5 mg/kg sugammadex, and 646 patients (25%) received 2.5 mg/kg sugammadex. In contrast, 128 patients (13%) received 2 mg/kg sugammadex, 362 patients (38%) received 2 ~ 2.5 mg/kg sugammadex and 462 patients (49%) received 2.5 mg/kg sugammadex in NM- group.This single-center retrospective study demonstrated that the use of intraoperative neuromuscular monitor reduced the reversal dose of sugammadex.

Chronic pain is increasingly recognized as an important comorbidity of HIV-infected patients, however, the exact molecular mechanisms of HIV-related pain are still elusive. CCAAT/enhancer binding proteins (C/EBPs) are expressed in various tissues, including the CNS. C/EBPβ, one of the C/EBPs, is involved in the progression of HIV/AIDS, but the exact role of C/EBPβ and its upstream factors are not clear in HIV pain state. Here, we used a neuropathic pain model of perineural HIV envelope glycoprotein gp120 application onto the rat sciatic nerve to test the role of phosphorylated C/EBPβ (pC/EBPβ) and its upstream pathway in the spinal cord dorsal horn (SCDH). HIV gp120 induced overexpression of pC/EBPβ in the ipsilateral SCDH compared with contralateral SCDH. Inhibition of C/EBPβ using siRNA against C/EBPβ reduced mechanical allodynia. HIV gp120 also increased TNFα, TNFRI, mitochondrial superoxide (mtO2·−), and pCREB in the ipsilateral SCDH. ChIP-qPCR assay showed that pCREB enrichment on the C/EBPβ gene promoter regions in rats with gp120 was higher than that in sham rats. Intrathecal TNF soluble receptor I (functionally blocking TNFα bioactivity) or knockdown of TNFRI using antisense oligodeoxynucleotide against TNFRI reduced mechanical allodynia, and decreased mtO2·−, pCREB and pC/EBPβ. Intrathecal Mito-tempol (a mitochondria-targeted O2·−scavenger) reduced mechanical allodynia and decreased pCREB and pC/EBPβ. Knockdown of CREB with antisense oligodeoxynucleotide against CREB reduced mechanical allodynia and lowered pC/EBPβ. These results suggested that the pathway of TNFα/TNFRI–mtO2·−–pCREB triggers pC/EBPβ in the HIV gp120-induced neuropathic pain state. Furthermore, we confirmed the pathway using both cultured neurons treated with recombinant TNFαin vitroand repeated intrathecal injection of recombinant TNFα in naive rats. This finding provides new insights in the understanding of the HIV neuropathic pain mechanisms and treatment.SIGNIFICANCE STATEMENTPainful HIV-associated sensory neuropathy is a neurological complication of HIV infection. Phosphorylated C/EBPβ (pC/EBPβ) influences AIDS progression, but it is still not clear about the exact role of pC/EBPβ and the detailed upstream factors of pC/EBPβ in HIV-related pain. In a neuropathic pain model of perineural HIV gp120 application onto the sciatic nerve, we found that pC/EBPβ was triggered by TNFα/TNFRI–mtO2·−–pCREB signaling pathway. The pathway was confirmed by using cultured neurons treated with recombinant TNFαin vitro, and by repeated intrathecal injection of recombinant TNFα in naive rats. The present results revealed the functional significance of TNFα/TNFRI–mtO2·−–pCREB–pC/EBPβ signaling in HIV neuropathic pain, and should help in the development of more specific treatments for neuropathic pain.

Morphine appears to be the most active metabolite of heroin; therefore, the effects of morphine are important in understanding the ramifications of heroin abuse. Opioid physical dependence (withdrawal response) may have very long-lasting effects on the motivation for reward, including the incubation of cue-induced drug-seeking behavior. However, the exact mechanisms of morphine withdrawal (MW) are not clear yet, and its treatment remains elusive. Periaqueductal gray (PAG) is one of the important sites in the pathogenesis of MW. Here, we used recombinant herpes simplex virus (HSV) vectors that encode the sod2 gene expressing manganese superoxide dismutase (MnSOD) to evaluate its therapeutic potential in MW. Microinjection of HSV vectors expressing MnSOD into the PAG reduced the MW syndrome. MnSOD vectors suppressed the upregulated mitochondrial superoxide, and endoplasmic reticulum stress markers (glucose-related protein 78 (GRP78) and activating transcription factor 6 alpha (ATF6α)) in the PAG induced by MW. Immunostaining showed that mitochondrial superoxide, GRP78 and ATF6α were colocalized with neuronal nuclei (a neuronal-specific marker), suggesting that they are located in the neurons in the PAG. These results suggest that overexpression of MnSOD by HSV vectors may relieve opioid dependence. This study may provide a novel therapeutic approach to morphine physical withdrawal response.

Background The caudal epidural block is one of the most commonly used regional anesthetic techniques in children. Administration of morphine via caudal injection enables analgesia, even for upper abdominal surgery. The thoracic paravertebral block has also been successfully used to treat perioperative pain during upper abdominal procedures in pediatric patients. Aim In the current study, we compared the two regional techniques for upper abdominal surgery in infants to determine whether one of them was preferable to the other. Methods Consecutive patients under 12 months of age who underwent upper abdominal surgery were retrospectively divided according to the chosen postoperative analgesia: Group C, caudal ropivacaine-morphine; Group P, paravertebral catheter. We analyzed the following outcomes: requirement for additional analgesics, pain scores, need for mechanical ventilation and oxygen dosage, postoperative blood pressure and heart rate, time to pass first stool, time until first full meal, and complications. Results Twenty-one consecutive patients were included: 10 in Group C and 11 in Group P. Median age at surgery was 80 (47.5−270.0) and 84.5 (34.3−287.5) days, respectively. No difference was found between the two groups in requirement for additional analgesics at 24 h after surgery (median 1 in Group C vs 1 in Group P, P = 0.288, 95% CI: −2 to 1). BOPS pain scores were only lower in Group P when compared to Group C at 24 h after surgery (median 1 vs 2, P = 0.041, 95% CI: −2 to 0). None of the patients had perioperative complications. Conclusions In this small series, there was no significant difference between caudal ropivacaine-morphine and paravertebral catheter for postoperative care in infants undergoing upper abdominal surgery. Further prospective studies are needed to compare the efficacy and incidence of complications of caudal block and paravertebral catheter for postoperative analgesia.

Background The long-term use of opioid analgesics is limited by the development of unwanted side-effects, such as tolerance. The molecular mechanisms of morphine anti-nociceptive tolerance are still unclear. The mitochondrial calcium uniporter (MCU) is involved in painful hyperalgesia, but the role of MCU in morphine tolerance has not been uncharacterised. Methods Rats received intrathecal injection of morphine for 7 days to induce morphine tolerance. The mechanical withdrawal threshold was measured using von Frey filaments, and thermal latency using the hotplate test. The effects of an MCU inhibitor, antisense oligodeoxynucleotide against cyclic adenosine monophosphate response element (CRE)-binding protein (CREB) or cytoplasmic polyadenylation element-binding protein 1 (CPEB1) in morphine tolerance were examined. Results Spinal morphine tolerance was associated with an increased expression of neuronal MCU, phospho-CREB (pCREB), and CPEB1 in the spinal cord dorsal horn. MCU inhibition increased the mechanical threshold and thermal latency, and reduced the accumulation of mitochondrial calcium in morphine tolerance. Intrathecal antisense oligodeoxynucleotide against CREB or CPEB1 restored the anti-nociceptive effects of morphine compared with mismatch oligodeoxynucleotide in von Frey test and hotplate test. Chromatin immunoprecipitation with quantitative PCR assay showed that CREB knockdown reduced the interaction of pCREB with the ccdc109a gene (encoding MCU expression) promoter and decreased the MCU mRNA transcription. RNA immunoprecipitation assay suggested that CPEB1 binds to the MCU mRNA 3′ untranslated region. CPEB1 knockdown decreased the expression of MCU protein. Conclusions These findings suggest that spinal MCU is regulated by pCREB and CPEB1 in morphine tolerance, and that inhibition of MCU, pCREB, or CPEB1 may be useful in preventing the development of opioid tolerance.

The goal of this study was to evaluate in patients with peripheral arterial disease (PAD) whether ultrasound-guided radial artery catheterization decreased procedural time and number of attempts compared with the traditional palpation technique.Ultrasonography was evaluated for arte- rial catheterization after the traditional palpation tech- nique was unsuccessful in 480 seconds in 10 patients with PAD. The vascular access was performed by a single anesthesiologist. The successful catheterization time and the number of attempts were recorded. We also measured the diameter of the radial artery, the skin-to-artery distance, and the distance between the linear probe and puncture site.The mean overall time per patient for catheter insertion was 220.0?112.6 sec in the ultra- sound group vs. 480 sec in the palpation group (P= 0.0029). The mean number of attempts was 1.30?0.48 in the ultrasound group vs. 4.50?0.53 in the palpation group (P = 0.0024). All catheterizations were success- ful, and no failure was encountered in the ultrasound group.Ultrasound-guided radial artery cath- eterization took less time to establish the arterial line, and it reduced the number of attempts when com- pared with the palpation technique.

Human immunodeficiency virus (HIV)-related neuropathic pain is a debilitating chronic condition that is severe and unrelenting. Despite the extensive research, the exact neuropathological mechanisms remain unknown, which hinders our ability to develop effective treatments. Loss of GABAergic tone may have an important role in the neuropathic pain state. Glutamic acid decarboxylase 67 (GAD67) is one of the isoforms that catalyze GABA synthesis. Here, we used recombinant herpes simplex virus (HSV-1) vectors that encode gad1 gene to evaluate the therapeutic potential of GAD67 in peripheral HIV gp120-induced neuropathic pain in rats. We found that (1) subcutaneous inoculation of the HSV vectors expressing GAD67 attenuated mechanical allodynia in the model of HIV gp120-induced neuropathic pain, (2) the anti-allodynic effect of GAD67 was reduced by GABA-A and-B receptors antagonists, (3) HSV vectors expressing GAD67 reversed the lowered GABA-IR expression and (4) the HSV vectors expressing GAD67 suppressed the upregulated mitochondrial superoxide and Wnt5a in the spinal dorsal horn. Taken together, our studies support the concept that recovering GABAergic tone by the HSV vectors may reverse HIV-associated neuropathic pain through suppressing mitochondrial superoxide and Wnt5a. Our studies provide validation of HSV-mediated GAD67 gene therapy in the treatment of HIV-related neuropathic pain.

Hirotsugu Kanda,1 Yuji Hirasaki,2 Takafumi Iida,1 Megumi Kanao-Kanda,1 Yuki Toyama,1 Takayuki Kunisawa,1 Hiroshi Iwasaki11Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan; 2Department of Anatomy, The Jikei University Graduate School of Medicine, Minato-ku, Tokyo, JapanPurpose: The aim of this study was to investigate fluid loading-induced changes in left ventricular end-diastolic volume (LVEDV) and stroke volume variability (SVV) in patients with end-stage renal disease (ESRD) using real-time three-dimensional transesophageal echocardiography and the Vigileo-FloTrac system.Patients and methods: After obtaining ethics committee approval and informed consent, 28 patients undergoing peripheral vascular procedures were studied. Fourteen patients with ESRD on hemodialysis (HD) were assigned to the HD group and 14 patients without ESRD were assigned to the control group. Institutional standardized general anesthesia was provided in both groups. SVV was measured using the Vigileo-FloTrac system. Simultaneously, a full-volume three-dimensional transesophageal echocardiography dataset was acquired to measure LVEDV, left ventricular end-systolic volume, and left ventricular ejection fraction. Measurements were obtained before and after loading 500 mL hydroxyethyl starch over 30 minutes in both groups.Results: In the control group, intravenous colloid infusion was associated with a significant decrease in SVV (13.8%±2.6% to 6.5%±2.6%, P

Background The cerebroprotective effect of retrograde cerebral perfusion (RCP) and selective antegrade cerebral perfusion (SCP) still remains controversial. Laser speckle flowgraphy has shown much promise for novel perioperative neuromonitoring by assessing blood flow of the optic nerve head. This study aimed to evaluate the cerebral microcirculation in humans using laser speckle flowgraphy during simple circulatory arrest, RCP, and SCP under moderate hypothermia and to investigate whether RCP under moderate hypothermia is a reliable method of cerebral protection. Methods A total of 23 consecutive patients who underwent a scheduled aortic arch or hemiarch surgical procedure on thoracic aorta aneurysm were enrolled. The laser speckle flowgraphy measurement that calculates mean blur ratio, a parameter of cerebral circulation, was obtained 6 times: after induction of anesthesia, baseline (T1), after initiation of cardiopulmonary bypass with cardiac arrest (T2), simple circulatory arrest (T3), RCP (T4), SCP (T5), and after the termination of cardiopulmonary bypass (T6). Results Both mean blur ratios of simple circulatory arrest and RCP were significantly decreased compared with baseline. In contrast, no significant differences were observed between simple circulatory arrest and RCP. The mean blur ratio of SCP was significantly increased compared with both simple circulatory arrest and RCP. Conclusions In conclusion, no significant difference was observed in the cerebral circulation between RCP and simple circulatory arrest without adjunctive strategy under moderate hypothermia. In contrast, the cerebral circulation during SCP was significantly higher than simple circulatory arrest and RCP. These results suggest that cerebral microcirculation may not be adequate during RCP compared with SCP under moderate hypothermia.

While effective antiretroviral treatment makes human immunodeficiency virus (HIV)-related death decreased dramatically, neuropathic pain becomes one of the most common complications in patients with HIV/acquired immunodeficiency syndrome (AIDS). The exact mechanisms of HIV-related neuropathic pain are not well understood yet, and no effective therapy is for HIV-pain. Evidence has shown that proinflammatory factors (e.g., tumor necrosis factor alpha (TNFα)) released from glia, are critical to contributing to chronic pain. Preclinical studies have demonstrated that non-replicating herpes simplex virus (HSV)-based vector expressing human enkephalin reduces inflammatory pain, neuropathic pain, or cancer pain in animal models. In this review, we describe recent advances in the use of HSV-based gene transfer for the treatment of HIV pain, with a special focus on the use of HSV-mediated soluble TNF receptor I (neutralizing TNFα in function) in HIV neuropathic pain model.

While effective antiretroviral treatment makes human immunodeficiency virus (HIV)-related death decreased dramatically, neuropathic pain becomes one of the most common complications in patients with HIV/acquired immunodeficiency syndrome (AIDS). The exact mechanisms of HIV-related neuropathic pain are not well understood yet, and no effective therapy is for HIV-pain. Evidence has shown that proinflammatory factors (e.g., tumor necrosis factor alpha (TNFα)) released from glia, are critical to contributing to chronic pain. Preclinical studies have demonstrated that non-replicating herpes simplex virus (HSV)-based vector expressing human enkephalin reduces inflammatory pain, neuropathic pain, or cancer pain in animal models. In this review, we describe recent advances in the use of HSV-based gene transfer for the treatment of HIV pain, with a special focus on the use of HSV-mediated soluble TNF receptor I (neutralizing TNFα in function) in HIV neuropathic pain model.

Hirotsugu Kanda,1 Yuji Hirasaki,2 Takafumi Iida,1 Megumi Kanao,1 Yuki Toyama,1 Takayuki Kunisawa,1 Hiroshi Iwasaki,11Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Asahikawa, 2Department of Anatomy, The Jikei University Graduate School of Medicine, Tokyo, JapanPurpose: The aim of this clinical trial was to investigate changes in stroke volume variability (SVV) and left ventricular end-diastolic volume (LVEDV) after a fluid bolus of crystalloid or colloid using real-time three-dimensional transesophageal echocardiography (3D-TEE) and the Vigileo-FloTrac™ system.Materials and methods: After obtaining Institutional Review Board approval, and informed consent from the research participants, 22 patients undergoing scheduled peripheral vascular bypass surgery were enrolled in the study. The patients were randomly assigned to receive 500 mL of hydroxyethyl starch (HES; HES group, n=11) or normal saline (Saline group, n=11) for fluid replacement therapy. SVV was measured using the Vigileo-FloTrac system. LVEDV, stroke volume, and cardiac output were measured by 3D-TEE. The measurements were performed over 30 minutes before and after the fluid bolus in both groups.Results: SVV significantly decreased after fluid bolus in both groups (HES group, 14.7%±2.6% to 6.9%±2.7%, P0.05). Stroke volume significantly increased after infusion in the HES group (50.6±12.5 mL to 61.6±19.1 mL, P0.05). Cardiac output measured by 3D-TEE significantly increased in the HES group (3.5±1.1 L/min to 3.9±1.3 L/min, P0.05).Conclusion: Administration of colloid and crystalloid induced similar responses in SVV. A higher plasma-expanding effect of HES compared to normal saline was demonstrated by the significant increase in LVEDV.Keywords: colloid–crystalloid controversy, fluid responsiveness, three-dimensional transesophageal echocardiography (3D-TEE)

OBJECTIVE To evaluate the morphologic changes of the mitral annulus using 3-dimensional transesophageal echocardiography during heart displacement to expose the anastomosis site in off-pump coronary artery bypass surgery (OPCAB). DESIGN Prospective case series. SETTING Single center, university hospital. PARTICIPANTS The study comprised 34 consecutive patients who underwent OPCAB of the left circumflex artery (LCX) and the right coronary artery (RCA). INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Mitral annulus parameters were measured using the Mitral Valve Quantification program after sternotomy (physiologic position) and during displacement of the heart to expose the LCX (LCX position) and the RCA (RCA position). The height of the mitral annulus was significantly lower in the LCX (5.76 ± 0.90 mm) and RCA (5.92 ± 0.97 mm) positions than in the physiologic position (6.96 ± 0.99 mm; both p < 0.0001). The percent change in the height of the mitral annulus was significantly greater in the mitral regurgitation group than in the mitral regurgitation nondeterioration group when in the LCX (-16.3% ± 6.0% v -11.9% ± 3.3%, p = 0.0203) and RCA (-16.9% ± 6.3% v -12.1% ± 3.8%, p = 0.0207) positions. The anteroposterior and intercommissural diameters, annulus perimeter, and surface area of the mitral annulus did not differ significantly among all heart positions. CONCLUSIONS The mitral annulus flattened and lost its saddle shape without expanding while in the LCX and RCA positions. The greater percent change in the height of the mitral annulus may aggravate mitral regurgitation.

Chronic pain is increasingly recognized as an important comorbidity of HIV-infected patients, however, the exact molecular mechanisms of HIV-related pain are still elusive. CCAAT/enhancer binding proteins (C/EBPs) are expressed in various tissues, including the CNS. C/EBPβ, one of the C/EBPs, is involved in the progression of HIV/AIDS, but the exact role of C/EBPβ and its upstream factors are not clear in HIV pain state. Here, we used a neuropathic pain model of perineural HIV envelope glycoprotein gp120 application onto the rat sciatic nerve to test the role of phosphorylated C/EBPβ (pC/EBPβ) and its upstream pathway in the spinal cord dorsal horn (SCDH). HIV gp120 induced overexpression of pC/EBPβ in the ipsilateral SCDH compared with contralateral SCDH. Inhibition of C/EBPβ using siRNA against C/EBPβ reduced mechanical allodynia. HIV gp120 also increased TNFα, TNFRI, mitochondrial superoxide (mtO2·−), and pCREB in the ipsilateral SCDH. ChIP-qPCR assay showed that pCREB enrichment on the C/EBPβ gene promoter regions in rats with gp120 was higher than that in sham rats. Intrathecal TNF soluble receptor I (functionally blocking TNFα bioactivity) or knockdown of TNFRI using antisense oligodeoxynucleotide against TNFRI reduced mechanical allodynia, and decreased mtO2·−, pCREB and pC/EBPβ. Intrathecal Mito-tempol (a mitochondria-targeted O2·−scavenger) reduced mechanical allodynia and decreased pCREB and pC/EBPβ. Knockdown of CREB with antisense oligodeoxynucleotide against CREB reduced mechanical allodynia and lowered pC/EBPβ. These results suggested that the pathway of TNFα/TNFRI–mtO2·−–pCREB triggers pC/EBPβ in the HIV gp120-induced neuropathic pain state. Furthermore, we confirmed the pathway using both cultured neurons treated with recombinant TNFα in vitro and repeated intrathecal injection of recombinant TNFα in naive rats. This finding provides new insights in the understanding of the HIV neuropathic pain mechanisms and treatment.

End-stage renal disease (ESRD) is associated with significant alterations in cardiovascular function; homeostasis of body fluid, electrolytes, and acid-base equilibrium; bone metabolism, erythropoiesis; and blood coagulation. The prevalence of ESRD is increasing rapidly worldwide, as is the number of patients requiring surgery under general anesthesia. Patients with ESRD have significantly higher risks of perioperative morbidity and mortality due to multiple comorbidities. The perioperative management of patients with ESRD under general anesthesia therefore requires special considerations and a careful multidisciplinary approach. In this review, the authors summarize the available literature to address common issues related to patients with ESRD and discuss the best perioperative approach for this patient subgroup.

We report three cases with systolic anterior motion (SAM) after mitral valve plasty. Preoperative mitral valve morphology is a risk factor for SAM. The morphological characteristics of SAM have been revealed in several studies. We found a small distance between coaptation and the interventricular septum in all cases, and cases 2, and 3 had a low AL/PL ratio, whereas case 3 had a large PML, which was revealed by transesophageal echocardiography. With the use of 3D transesophageal echocardiography, when mitral valve prolapse was investigated, in all three cases, it was easy to specify lesions. The issue for the future is 3D analysis when SAM is occurring.

Chronic opiates induce the development of physical dependence. Opioid physical dependence characterized by withdrawal symptoms, may have very long-lasting effects on the motivation for reward, including the incubation of cue-induced drug-seeking behavior. Elucidation of the mechanisms involved in physical dependence is crucial to developing more effective treatment strategies for opioid dependence. Chronic morphine induces production of proinflammatory cytokines in regional-specific sites of the brain. Interleukin-4 (IL-4) is a prototypical anti-inflammatory cytokine that globally suppresses proinflammatory cytokines. Here, we used recombinant herpes simplex virus vector S4IL4 that encode mouse il4 gene to evaluate the therapeutic potential of IL-4 in naloxone-precipitation morphine withdrawal (MW). One week after microinjection of the vector S4IL4 into the PAG LacZ or mouse IL-4 immunoreactivity in the vlPAG was visualized. ELISA assay showed that vector S4IL4 into the PAG induced the expression of IL-4. S4IL4 blunted the morphine withdrawal syndrome. S4IL4 suppressed the upregulated TNFα, NR2B and pC/EBPβ in the PAG induced by MW. These results show that inhibition of proinflammatory factor in the PAG suppressed MW. This study may provide a novel therapeutic approach to morphine physical withdrawal symptoms.

Thoracic paravertebral block (TPVB) has proven to be safer by using ultrasound imaging. This prospective randomized study was designed to investigate postoperative pain relief and intraoperative hemodynamics in patients undergoing ultrasound-guided TPVB or epidural analgesia.Twelve patients scheduled for thoracoscopic surgery for lung cancer were randomly divided into two groups and received ultrasound guided TPVB (N=6) or epidural analgesia (N=6). Both groups received postoperative analgesia with continuous infusion of 0.2% ropivacaine 6 ml · hr(-1) via paravertebral or epidural block. Postoperative numeric rating score (NRS) and the data of intraoperative hemodynamics were collected.In comparison with the epidural group, the level of NRS was higher in the TPVB group at 12 hr (4.5±1.05 vs 2.7±0.82, P0.01), and 24 hr (4.5±1.05 vs 2.7±0.82, P0.01) after surgery. In the TPVB group, the intraoperative amount of transfusion was smaller (1,331±147 ml vs 1,693±162 ml, P0.01) and the lowest systolic pressure was higher (87±4.56 mmHg vs 73±4.34 mmHg, P0.01) than that of the epidural group.Ultrasound guided TPVB was performed affecting hemodynamics less than the epidural anesthetic. There was less postoperative analgesic effect on TPBV than on epidural analgesia after thora- coscopic surgery when continuously infusing 0.2% ropivacaine 6 ml · hr(-1).

Objective Sodium butyrate (butyric acid; BA) is a major metabolic by-product of the anaerobic periodontopathic bacteria present in subgingival plaque. We examined the effects of BA and/or indomethacin on cell proliferation, the expression of cyclooxygenases (COXs), prostaglandin (PG) receptors (EP1-4), extracellular matrix proteins, such as type I collagen and osteopontin, and PGE2 production, using ROS17/2.8 cells as osteoblasts. Methods The rat clonal cell line ROS 17/2.8 was cultured with 0, 10−5, 10−4, and 10−3 M BA in the presence or absence of 0.5 μM indomethacin, for up to 7 days. The expression of COX-1, COX-2, EP1, EP2, EP3, EP4, type I collagen, and osteopontin was examined at the mRNA and protein levels using real-time PCR and Western blotting, respectively. The amount of PGE2 in the culture medium was measured by ELISA. Results Proliferation of ROS 17/2.8 cells was not affected by the addition of BA. However, PGE2 production and the expression of COX-1 and COX-2 increased with the addition of BA. In contrast, indomethacin, an inhibitor of COX, blocked the stimulatory effect of BA. Furthermore, EP2 expression increased with BA treatment, whereas EP1 expression was not affected and the expression of EP3 and EP4 was not detected. The addition of BA also increased the expression of type I collagen and osteopontin. Indomethacin blocked about 50% of the stimulatory effect of BA on type I collagen, whereas it did not block the effect on osteopontin. Conclusions These results suggest that BA induces PGE2 production by increasing the expression of COX-1 and COX-2 in osteoblasts, and that an autocrine action of the produced PGE2, via EP1 or BA-induced EP2, is related to an increase in type I collagen expression by BA.

Mitochondria play an important role in many cellular and physiologic functions. Mitochondria are dynamic organelles, and their fusion and fission regulate cellular signaling, development, and mitochondrial homeostasis. The most common complaint of human immunodeficiency virus (HIV)-sensory neuropathy is pain on the soles in patients with HIV, but the exact molecular mechanisms of HIV neuropathic pain are not clear. In the present study, we investigated the role of mitochondrial dynamin-related protein 1 (Drp1, a GTPase that mediates mitochondrial fission) in the perineural HIV coat glycoprotein gp120-induced neuropathic pain state.Neuropathic pain was induced by the application of recombinant HIV-1 envelope protein gp120 into the sciatic nerve. Mechanical threshold was tested using von Frey filaments. The mechanical threshold response was assessed over time using the area under curves. Intrathecal administration of antisense oligodeoxynucleotide (ODN) against Drp1, mitochondrial division inhibitor-1 (mdivi-1), or phenyl-N-tert-butylnitrone (a reactive oxygen species scavenger) was given. The expression of spinal Drp1 was examined using western blots. The expression of mitochondrial superoxide in the spinal dorsal horn was examined using MitoSox imaging.Intrathecal administration of either antisense ODN against Drp1 or mdivi-1 decreased mechanical allodynia (a sensation of pain evoked by nonpainful stimuli) in the gp120 model. Intrathecal ODN or mdivi-1 did not change basic mechanical threshold in sham surgery rats. Intrathecal Drp1 antisense ODN decreased the spinal expression of increased Drp1 protein induced by peripheral gp120 application. Intrathecal phenyl-N-tert-butylnitrone reduced mechanical allodynia. Furthermore, both intrathecal Drp1 antisense ODN and mdivi-1 reversed the upregulation of mitochondrial superoxide in the spinal dorsal horn in the gp120 neuropathic pain state.These data suggest that mitochondrial division plays a substantial role in the HIV gp120-related neuropathic pain state through mitochondrial reactive oxygen species and provides evidence for a novel approach to treating chronic pain in patients with HIV.

Recent advancement in ultrasound technology allows us to visualize detailed structures around the airway. One of the important roles of the airway ultrasound is to identify cricothyroid membrane where the emergent invasive access should be performed. Now we can assess the risk of difficult cricothyroidotomy before anesthesia of which the new ASA difficult airway guideline suggests. Airway ultrasound can also be used to confirm correct position of the tracheal tube and laryngeal mask, difficult laryngoscopy prediction in obese patients, assessing vocal cord function, prediction of the post extubation stridor, and so on. We also introduce perioperative evaluation of the airway via sonography (PEAS) protocol in this review.

Publisher, BACKGROUND: Olprinone decreases the cardiac preload and/or afterload because of its vasodilatory effect and increases myocardial contractility by inhibiting phosphodiesterase III. PURPOSE: The objective of this study was to characterize the population pharmacokinetics of olprinone after a single continuous infusion in healthy male volunteers. METHODS: We used 500 plasma concentration data points collected from nine healthy male volunteers for the study. The population pharmacokinetic analysis was performed using the nonlinear mixed effect model (NONMEM®) software. RESULTS: The time course of plasma concentration of olprinone was best described using a two-compartment model. The final pharmacokinetic parameters were total clearance (7.37 mL/minute/kg), distribution volume of the central compartment (134 mL/kg), intercompartmental clearance (7.75 mL/minute/kg), and distribution volume of the peripheral compartment (275 mL/kg). The interindividual variability in the total clearance was 12.4%, and the residual error variability (exponential and additive) were 22.2% and 0.129 (standard deviation). The final pharmacokinetic model was assessed using a bootstrap method and visual predictive check. CONCLUSION: We developed a population pharmacokinetic model of olprinone in healthy male adults. The bootstrap method and visual predictive check showed that this model was appropriate. Our results might be used to develop the population pharmacokinetic model in patients

1128 November 2012 W HEN difficulty with airway management is anticipated, standard guidelines recommend that the airway is secured in the awake patient.1 In the “cannot intubate, cannot ventilate” situation, surgical or cannula cricothyroidotomy is required.1 However, identification of the cricothyroid membrane by palpation is frequently inaccurate, even under elective conditions.2 Preoperative evaluation of the anterior neck with an ultrasound may be a viable technique of increasing the safety of cricothyroidotomy. An 82-yr-old man with a difficult intubation profile as a consequence of cervical spine disease was scheduled for percutaneous nephrolithotripsy in the prone position. Before awake fiberoptic intubation, his neck was scanned with an ultrasound linear probe to identify the cricothyroid membrane. Because he had a history of hypertension and ischemic heart disease, we decided to apply tracheal anesthesia before intubation. The distance from skin surface to the membrane was measured as 0.84 cm, and neither vessel nor abnormal structure was observed. Cannula cricothyroidotomy was then performed with a 22G intravenous catheter under ultrasonographic guidance in an out-of-plane configuration, because this is a more reliable technique of achieving exact midline puncture.3 The figure shows the anterior-posterior view of the larynx and sternocleidomastoid muscle (asterisk) as the cannula (arrow) enters the cricothyroid membrane (dashed line) from the 12 o’clock direction. As soon as loss-of-resistance sensation was detected, air was aspirated. Lidocaine was injected through the cannula, and then fiberoptic bronchoscope intubation was performed uneventfully. Preoperative examination of the larynx with sonography can accurately identify the cricothyroid membrane and may provide other anatomical information. Though the cricothyroid membrane puncture is less frequently used to achieve airway anesthesia, ultrasound guidance may improve safety whenever this technique is used, including prophylactic and emergency cannula cricothyroidotomy.

Ceramide sulfate (N-acylsphingosine-1-O-sulfate), which lacks the galactose residue of sulfatide, was examined as a possibly preferable constituent of liposomes for drug delivery. Multilamellar vesicles prepared from phosphatidylcholine, cholesterol, and N-lignoceroylsphingosine-1-O-sulfate in a molar ratio of 5:4:1 efficiently entrapped adriamycin, and the retention of the drug in the liposomes in saline at 4 degrees C for 8 d was nearly 100%. In terms of entrapment efficiency and retention of the drug in liposomes, N-lignoceroylsphingosine-1-O-sulfate was superior to N-stearoylsphingosine-1-O-sulfate. A pharmacodynamic study revealed that the blood level of adriamycin was far higher with the drug encapsulated in N-lignoceroylsphingosine-1-O-sulfate-containing liposomes than with the free drug. The drug level in the heart was remarkably reduced with the liposome-entrapped drug, which is advantageous in reducing the cardiotoxicity of this drug. The effect of N-lignoceroylsphingosine-1-O-sulfate-containing liposomes on the blood level of adriamycin was superior to that of sulfatide-containing liposomes, though the effect of the former on the heart level was comparable to that of the latter. The tumoricidal effect on ascitic P388 leukemia and Lewis lung carcinoma was higher with adriamycin entrapped in N-lignoceroylsphingosine-1-O-sulfate-containing liposomes than with the free drug.

Sodium butyrate (butyric acid; BA) is a major metabolic by-product of the anaerobic periodontopathic bacteria present in subgingival plaque. We examined the effects of BA and/or indomethacin on cell proliferation, the expression of cyclooxygenases (COXs), prostaglandin (PG) receptors (EP1-4), extracellular matrix proteins, such as type I collagen and osteopontin, and PGE(2) production, using ROS17/2.8 cells as osteoblasts.The rat clonal cell line ROS 17/2.8 was cultured with 0, 10(-5), 10(-4), and 10(-3)M BA in the presence or absence of 0.5 μM indomethacin, for up to 7 days. The expression of COX-1, COX-2, EP1, EP2, EP3, EP4, type I collagen, and osteopontin was examined at the mRNA and protein levels using real-time PCR and Western blotting, respectively. The amount of PGE(2) in the culture medium was measured by ELISA.Proliferation of ROS 17/2.8 cells was not affected by the addition of BA. However, PGE(2) production and the expression of COX-1 and COX-2 increased with the addition of BA. In contrast, indomethacin, an inhibitor of COX, blocked the stimulatory effect of BA. Furthermore, EP2 expression increased with BA treatment, whereas EP1 expression was not affected and the expression of EP3 and EP4 was not detected. The addition of BA also increased the expression of type I collagen and osteopontin. Indomethacin blocked about 50% of the stimulatory effect of BA on type I collagen, whereas it did not block the effect on osteopontin.These results suggest that BA induces PGE(2) production by increasing the expression of COX-1 and COX-2 in osteoblasts, and that an autocrine action of the produced PGE(2), via EP1 or BA-induced EP2, is related to an increase in type I collagen expression by BA.

Pharmacokinetics and antineoplastic effect of adriamycin (ADM) entrapped in multilamellar vesicles of liposomes composed of egg phosphatidylcholine (PC), cholesterol (Chol), and cholesterol sulfate (CholSO4) in a molar ratio of 6:3:1 were studied. Upon its intravenous injection, the blood level of ADM remained higher for 24h than that of ADM entrapped in liposomes composed of PC, Chol, and sulfatide (CSE) in a molar ratio of 5:4:1 and than that of free ADM. Entrapment of ADM in liposomes containing either CholSO4 or CSE reduced the concentration of ADM in the heart and kidney compared with free ADM. In the liver, however, the level of ADM, when the drug entrapped in CholSO4-containing liposomes was injected, was similar to that of ADM injected in free form, while the drug markedly accumulated in this organ, when ADM was entrapped in CSE-containing liposomes. By using P388 leukemia of mice, we demonstrated that ADM entrapped in CholSO4-containing liposomes has higher antineoplastic activity than free ADM.

Cholesterol sulfate (CholSO4) was found to be a useful substitute of sulfatide for the preparation of negatively charged liposomes entrapping adriamycin (ADM). Liposomes composed of egg phosphatidylcholine, cholesterol, and CholSO4 in a molar ratio of 6:3:1 entrapped ADM efficiently and reduced the leakage of the entrapped ADM from the liposomes to the same degree as found for sulfatide-containing liposomes. The novel liposomes induced neither haemolysis nor platelet aggregation

To the Editor: When airway management is anticipated to be difficult, awake intubation using a fiberoptic bronchoscope (FOB) is indicated [1]. To achieve successful awake intubation, patient cooperation in combination with appropriate local anesthesia is essential. Superior laryngeal nerve block (SLNB) is an airway anesthesia technique that can paralyze the lingual radix, epiglottis, and cricothyroid muscle, and is thus expected to suppress the gag and cough reflexes. SLNB has conventionally been performed with palpation of the greater horn of the hyoid as an anatomical landmark. The needle is inserted in an anteroinferomedial direction until the lateral aspect of the greater horn is contacted, and local anesthetic is then injected while the carotid artery is displaced posteriorly. However, it is sometimes difficult to recognize landmarks when the patient is obese or has an anatomical abnormality due to a pathology. Ultrasound-guided nerve block has been widely used recently, and this technique can provide visual information on the anatomy [2]. Here, we report a case in which awake tracheal intubation was performed under ultrasound-guided bilateral SLNB. A 19-year-old female complained of submental pain after odontotherapy, and she was scheduled for incisional drainage of a laryngeal abscess. As the abscess involved the medial pterygoid muscle (Fig. 1a), she presented restricted mouth opening (less than one finger). After obtaining written informed consent, semi-awake FOB intubation under nerve block was scheduled. Prior to nasal FOB intubation, 2 mg of midazolam and 50 lg of fentanyl were administered. Nasal mucosa was topicalized with 8 % lidocaine. Although we attempted to perform SLNB, her left hyoid bone was difficult to find by palpation. However, when we scanned her neck using US (5–10 MHz linear probe, S-Nerve, Sonosite Japan, Tokyo, Japan), the bone was easily identified in the transverse view. The distance from the skin surface to the bone was measured as 1.1 cm, and neither vessel nor abnormal structure was observed. With a 22G needle, 2 ml of 2 % lidocaine were injected into the surface of the greater horn of the hyoid under ultrasound guidance in an in-plane configuration (Fig. 1b). The procedure was repeated on the right side. The tracheal membrane was also topicalized with ultrasound-guided translaryngeal block through the cricothyroid membrane. Ultrasound-guided SLNB seemed effective and FOB intubation was successfully performed while the patient was semi-awake without any discomfort. The patient complained of slight hoarseness after surgery but this disappeared within a day. There was no other notable complication. We have previously reported ultrasound-guided translaryngeal block through the cricothyroid membrane for awake The work was attributed to both the Department of Anesthesiology and Critical Care Medicine and the Department of Emergency Medicine and Intensive Care at Asahikawa Medical University.

tainment of human rights in contemporary Japanese society, while the Koreans in Japan, as marginal figures, continue to face the problem of their identity. These issues have been studied from political and historical perspectives, but with an insufficient religious and cultural understanding. The group of "Korean temples" in the suburbs of Osaka, where the largest number of Koreans inJapan reside, is a religious phenomenon consisting of a syncretism of Korean Shamanism, Korean Buddhism, and Japanese mountain religion. In this paper I will outline the present situation of these Korean temples in Japan and reflect on the significance they hold for the Koreans inJapan andJapanese society. The "resentment" (han 'tR ) of the spirits of the dead, which is to be purified through shamanistic rituals, is a religious expression of the collective misfortune of the Koreans inJapan which is continually reproduced by the structural discrimination ofJapanese society. Also, this Shamanism has served as a magical way for Korean women in Japan to adjust to their difficult social situation. It also contains, as the basic ethnic culture of Koreans in Japan, the potential to serve as a womb for the formation of their culture and identity.

Human immunodeficiency virus (HIV) patients treated with nucleoside reverse transcriptase inhibitors (NRTIs), have been known to develop neuropathic pain. While there has been a major shift away from some neurotoxic NRTIs in current antiretroviral therapy, a large number of HIV patients alive today have previously received them, and many have developed painful peripheral neuropathy. The exact mechanisms by which HIV with NRTIs contribute to the development of neuropathic pain are not known. Previous studies suggest that cytoplasmic polyadenylation element-binding protein (CPEB), reactive oxygen species (ROS), and cAMP-response element-binding protein (CREB)-binding protein (CBP), are involved in the neuroimmunological diseases including inflammatory/neuropathic pain. In this study, we investigated the role of CPEB, mitochondrial ROS (mtROS), or CBP in neuropathic pain induced by HIV envelope protein gp120 combined with antiretroviral drug. The application of recombinant gp120 into the sciatic nerve plus systemic ddC (one of NRTIs) induced mechanical allodynia. Knockdown of CPEB or CBP using intrathecal antisense oligodeoxynucleotide (AS-ODN) reduced mechanical allodynia. Intrathecal mitochondrial superoxide scavenger mito-tempol (Mito-T) increased mechanical withdrawal threshold. Knockdown of CPEB using intrathecal AS-ODN, reduced the up-regulated mitochondrial superoxide in the spinal dorsal horn in rats with gp120 combined with ddC. Intrathecal Mito-T lowered the increased expression of CBP in the spinal dorsal horn. Immunostaining studies showed that neuronal CPEB positive cells were co-localized with MitoSox positive profiles, and that MitoSox positive profiles were co-localized with neuronal CBP. Our studies suggest that neuronal CPEB-mtROS-CBP pathway in the spinal dorsal horn, plays an important role in the gp120/ddC-induced neuropathic pain in rats.