Sangseok Lee

A Small Volatile Bacterial Molecule Triggers Mitochondrial Dysfunction in Murine Skeletal Muscle

Mitochondria integrate distinct signals that reflect specific threats to the host, including infection, tissue damage, and metabolic dysfunction; and play a key role in insulin resistance. We have found that the Pseudomonas aeruginosa quorum sensing infochemical, 2-amino acetophenone (2-AA), produced during acute and chronic infection in human tissues, including in the lungs of cystic fibrosis (CF) patients, acts as an interkingdom immunomodulatory signal that facilitates pathogen persistence, and host tolerance to infection. Transcriptome results have led to the hypothesis that 2-AA causes further harm to the host by triggering mitochondrial dysfunction in skeletal muscle. As normal skeletal muscle function is essential to survival, and is compromised in many chronic illnesses, including infections and CF-associated muscle wasting, we here determine the global effects of 2-AA on skeletal muscle using high-resolution magic-angle-spinning (HRMAS), proton (1H) nuclear magnetic resonance (NMR) metabolomics, in vivo 31P NMR, whole-genome expression analysis and functional studies. Our results show that 2-AA when injected into mice, induced a biological signature of insulin resistance as determined by 1H NMR analysis-, and dramatically altered insulin signaling, glucose transport, and mitochondrial function. Genes including Glut4, IRS1, PPAR-γ, PGC1 and Sirt1 were downregulated, whereas uncoupling protein UCP3 was up-regulated, in accordance with mitochondrial dysfunction. Although 2-AA did not alter high-energy phosphates or pH by in vivo 31P NMR analysis, it significantly reduced the rate of ATP synthesis. This affect was corroborated by results demonstrating down-regulation of the expression of genes involved in energy production and muscle function, and was further validated by muscle function studies. Together, these results further demonstrate that 2-AA, acts as a mediator of interkingdom modulation, and likely effects insulin resistance associated with a molecular signature of mitochondrial dysfunction in skeletal muscle. Reduced energy production and mitochondrial dysfunctional may further favor infection, and be an important step in the establishment of chronic and persistent infections.

The effect of remifentanil versus N2O on postoperative pain and emergence agitation after pediatric tonsillectomy/adenoidectomy

Background Remifentanil can be an alternative to N2O in general anesthesia. Intraoperative remifentanil may lead to acute opioid tolerance. This study aims to assess the effect of remifentanil substituted for 70% N2O on postoperative pain in children undergoing tonsillectomy/adenoidectomy. In addition, we evaluated the effect of remifentanil infusion on incidence of emergence agitation in these patients. Methods Eighty children, aged 2-12 years, undergoing tonsillectomy/adenoidectomy were randomly allocated to the N2O group (Group N; n = 40, sevoflurane and 70% N2O) or remifentanil group (Group R; n = 40, sevoflurane with remifentanil infusion at the rate of 0.17 µg/kg/min). In the recovery room, severity of pain and agitation were assessed by an investigator blinded to the assigned group. Time to eye opening and incidence of severe pain and agitation were compared between groups. Logistic regression was used to identify factors related to occurrence of severe pain and agitation. Results Number of patients with severe postoperative pain was 6 and 16 in groups N and R, respectively (P = 0.012). Incidence of emergence agitation was not significantly different between groups. Remifentanil infusion was a significant factor related to the occurrence of severe postoperative pain (P = 0.015), and age was inversely related to occurrence of emergence agitation (P = 0.001). Conclusions In children undergoing tonsillectomy/adenoidectomy, intraoperative remifentanil infusion may increase incidence of severe postoperative pain compared to N2O, but it may not affect incidence of emergence agitation.

Nonsurgically induced disuse muscle atrophy and neuromuscular dysfunction upregulates alpha7 acetylcholine receptors

Previous models of muscle disuse have invariably used surgical methods that require the repetitive application of plaster casts. A method of disuse atrophy that does not require such repetitive applications is described herein. Modified plastic pipette tubing was applied to a single hindlimb (mouse), from thigh to foot, resulting in immobilization of the knee in the extension position, and the ankle in the plantar flexion position. This method resulted in the loss of soleus muscle to 11%, 22%, 39%, and 45% of its original mass at 3, 7, 14, and 21 days, respectively, in association with a significant decrease of tibialis twitch (25%) and tetanic tensions (26%) at 21 days, compared with the contralateral side and (or) sham-immobilized controls. Immunohistochemical analysis of the soleus using fluorescent α-bungarotoxin revealed a significant increase in the number of synapses per unit area (818 + 31 compared with 433 + 16/mm(2)) and an increase in muscle fibers per unit area (117 compared with 83/mm(2)), most likely related to the atrophy of muscle fibers bringing synapses closer. A 3-fold increase in alpha7 acetylcholine receptor (α7AChR) protein expression, along with increased expression of α1AChR subunit in the immobilized side compared with the contralateral side was observed. The physiology and pharmacology of the novel finding of upregulation of α7AChRs with disuse requires further study.

The comparative study to evaluate the effect of palonosetron monotherapy versus palonosetron with dexamethasone combination therapy for prevention of postoperative nausea and vomiting

Background 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are effective and safe on postoperative nausea and vomiting (PONV). Palonosetron, the newest 5-HT3 antagonist, has potent antiemetic property. We hypothesized that a combination of palonosetron and dexamethasone could more decrease PONV than palonosetron alone. Methods Among the patients scheduled to undergo laparoscopic gynecologic surgery, mastoidectomy with tympanoplasty or thyroidectomy under general anesthesia, eighty four female patients with at least two PONV risk factors were enrolled in this study. They were received randomly 0.075 mg palonosetron and 4 mg dexamethasone (group C) or 0.075 mg palonosetron alone (group P). The severity of PONV using Rhodes index and the percentage of complete response during postoperative 24 hours were compared between groups. Results The frequency of mild/moderate/great/severe PONV based on Rhodes index were 9.8%/0%/0%/0% and 9.3%/2.3%/2.3%/0% in group P and group C, respectively. Complete response for PONV was observed in 90.2% and 86% of patients in group P and group C, respectively. The overall incidence of PONV in group P and C was 9.8% and 14%, respectively. There was no significant difference between the two groups. Conclusions There were no differences between palonosetron monotherapy and combination therapy of palonosetron and dexamethasone in patients with high emetogenic risk.

Prediction of Plasma Hemoglobin Concentration by Near-Infrared Spectroscopy

The estimation of plasma hemoglobin concentration (Hb) is among one of the daily activities in the practice of clinical anesthesiology. The near-infrared spectroscopy of the brain (rSO2) represents a balance between cerebral oxygen delivery and consumption. This study was designed to assess the value of rSO2 in the prediction of the Hb level while other variables were mathematically controlled. Thirty healthy adult patients undergoing spine surgery, expected to have a moderate degree of intraoperative bleeding, were enrolled in this study. General anesthesia was given and ventilation was mechanically controlled. Measurement of Hb and PaCO2 were performed at random periods of time. We obtained a total of 97 data combinations for the 30 study patients. The Hb was regressed by independent variables including rSO2 and PaCO2. A multilinear regression analysis was performed and the final regression equation was expressed only with statistically significant variables. The measured Hb was tightly regressed with three variables. The final regression equation was Hb=+8.580+0.238 rSO2-0.338 PaCO2-0.004 anesthetic exposure duration (Tmin) (p=0.000, r2=0.809). Near-infrared spectroscopy was shown to be a valuable predictor of plasma Hb in the clinical anesthesiology setting.

Statistical and methodological considerations for reporting RCTs in medical literature

Randomized controlled trials (RCTs) are known to provide the most reliable evidence on intervention. However, RCTs are often conducted and reported incompletely and inadequately, making readers and reviewers unable to judge the validity and reliability of the trials. In this article, we consider the statistical and methodological issues involved in reporting on RCTs, particularly in relation to the objectives, designs, and commencements of trials. This paper deals with the various issues that should be considered in presenting RCTs, and suggests checklists for reporting on them. We expect that these checklists will remind readers and reviewers to evaluate manuscripts systematically and comprehensively, making those manuscripts more transparent and reliable.

Standard deviation and standard error of the mean

In most clinical and experimental studies, the standard deviation (SD) and the estimated standard error of the mean (SEM) are used to present the characteristics of sample data and to explain statistical analysis results. However, some authors occasionally muddle the distinctive usage between the SD and SEM in medical literature. Because the process of calculating the SD and SEM includes different statistical inferences, each of them has its own meaning. SD is the dispersion of data in a normal distribution. In other words, SD indicates how accurately the mean represents sample data. However the meaning of SEM includes statistical inference based on the sampling distribution. SEM is the SD of the theoretical distribution of the sample means (the sampling distribution). While either SD or SEM can be applied to describe data and statistical results, one should be aware of reasonable methods with which to use SD and SEM. We aim to elucidate the distinctions between SD and SEM and to provide proper usage guidelines for both, which summarize data and describe statistical results.

Effect of ramosetron on shivering during spinal anesthesia

Background Shivering associated with spinal anesthesia is uncomfortable and may interfere with monitoring. The aim of this study is to evaluate the effect of ramosetron, a serotonin-3 receptor antagonist, on the prevention of shivering during spinal anesthesia. Methods We enrolled 52 patients who were ASA I or II and who had undergone knee arthroscopy under spinal anesthesia. Warmed (37°) lactated Ringers solution was infused over 15 minutes before spinal anesthesia. Patients were randomly allocated to a control group (group S, N = 26) or study group (group R, N = 26). Spinal anesthesia was performed with a 25-G Quincke-type spinal needle between the lumbar 3-4 interspace with 2.2 ml 0.5% hyperbaric bupivacaine. For patients allocated in groups S and R, 2 ml 0.9% saline and 0.3 mg ramosetron, respectively, was intravenously injected immediately before intrathecal injection at identical times. Shivering and spinal block levels were assessed immediately after the completion of subarachnoid injection, as well as 5, 10, 15, 20, 25, 30, 60, and 120 minutes after spinal anesthesia. Systolic and diastolic blood pressures, heart rate, and peripheral oxygen saturation were also recorded. Core temperatures were measured by tympanic thermometer and recorded before and during spinal anesthesia at 30-minute intervals. Results Shivering was observed in 2 patients in group R and 9 patients in group S (P = 0.038, odds ratio = 6.14, 95% C.I. = 1.08-65.5). The difference in core temperature between the groups was not significant. Conclusions Compared to control, ramosetron is an effective way to prevent shivering during spinal anesthesia.

General anesthesia versus monitored anesthetic care with dexmedetomidine for closed reduction of nasal bone fracture

Background Reduction of nasal bone fracture can be performed under general or local anesthesia. The aim of this study was to compare general anesthesia (GA) and monitored anesthetic care (MAC) with dexmedetomidine based on intraoperative vital signs, comfort of patients, surgeons and nurses and the adverse effects after closed reduction of nasal bone fractures. Methods Sixty patients with American Society of Anesthesiologists physical status I or II were divided into a GA group (n = 30) or MAC group (n = 30). Standard monitorings were applied. In the GA group, general anesthesia was carried out with propofol-sevoflurane-N2O. In the MAC group, dexmedetomidine and local anesthetics were administered for sedation and analgesia. Intraoperative vital signs, postoperative pain scores by visual analog scale and postoperative nausea and vomiting (PONV) were compared between the groups. Results Intraoperatively, systolic blood pressures were significantly higher, and heart rates were lower in the MAC group compared to the GA group. There were no differences between the groups in the patient, nurse and surgeons satisfaction, postoperative pain scores and incidence of PONV. Conclusions MAC with dexmedetomidine resulted in comparable satisfaction in the patients, nurses and surgeons compared to general anesthesia. The incidence of postoperative adverse effects and severity of postoperative pain were also similar between the two groups. Therefore, both anesthetic techniques can be used during the reduction of nasal bone fractures based on a patient%s preference and medical condition.

A comparative evaluation of humidifier with heated wire breathing circuit under general anesthesia

BACKGROUND Dry and cold anesthetic gas deteriorates patients respiratory function and body heat balance. We examined whether a humidifier with heated wire circuit might maintain core temperature and humidity of inspired gas in patient undergoing general anesthesia. METHODS We enrolled forty ASA physical status I, II patients under general anesthesia for this study. We allocated the patients randomly into two groups with (experimental group) or without (control group) Humitube(R) anesthesia circuit, which delivered heated and humidified inspired anesthetic gases. We recorded the temperatures and humidity of the inspired gases throughout the surgery. RESULTS The temperatures and relative humidity of the inspired gases in experimental group were significantly greater compared to control group (36.2 +/- 0.9degrees C, 89.5 +/- 4.8% vs. 30.4 +/- 1.8degrees C, 37.9 +/- 5.9%, P < 0.05) during anesthesia. The core temperatures in experimental group were significantly greater compared to control group (36.1 +/- 0.3degrees C vs. 35.7 +/- 0.1degrees C, P < 0.05) during anesthesia. CONCLUSIONS A humidifier with heated wire system for anesthesia breathing circuit is helpful to maintain core temperature and adequate humidity.