Young Hoon Yoon

Effects of hypertonic saline on macrophage migration inhibitory factor in traumatic conditions

Trauma-induced suppression of cellular immune function contributes to sepsis, multiple organ dysfunction syndrome (MODS) and mortality. Macrophage migration inhibitory factor (MIF) has been revealed to be central to several immune responses. However, the role of MIF in trauma-like conditions is unknown. Therefore, the present study evaluated MIF in macrophages and polymorphonuclear neutrophils (PMNs). The effects of hypertonic saline (HTS) on lipopolysaccharide (LPS)-induced MIF levels were evaluated in macrophages. MIF concentrations were determined by an enzyme-linked immnosorbent assay (ELISA) and cell lysates were used for western blot analysis. The effects of HTS on N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced MIF were evaluated in PMNs. MIF concentrations were determined by ELISA, western blotting and real time-polymerase chain reaction (RT-PCR) to determine MIF expression. MIF levels, which were measured by the ELISA, increased by 1.24±0.38 ng/ml in the supernatants of LPS-stimulated macrophages compared with the controls (0.79±0.07 ng/ml) at 2 h. HTS10 (150 mmol/l) partially restored MIF levels (0.84±0.22 ng/ml; P<0.05). Also, western blotting was performed and MIF protein levels were higher in the LPS-stimulated macrphages (20% increase in band density) compared with the controls (P<0.05). The addition of HTS decreased MIF protein expression. MIF levels in fMLP-stimulated PMN cells were unchanged compared with the controls according to the ELISA, western blotting and RT-PCR. No effects were observed following treatment with HTS. MIF concentrations and MIF expression were higher in LPS-stimulated macrophages than controls and HTS restored MIF levels to those of the controls. MIF levels were unchanged in PMNs stimulated by fMLP.

The additional use of end-tidal alveolar dead space fraction following D-dimer test to improve diagnostic accuracy for pulmonary embolism in the emergency department

Purpose To determine the diagnostic performance of bedside assessment of end-tidal alveolar dead space fraction (ADSF) for pulmonary embolism (PE) and whether the use of additional ADSF assessment following D-dimer assay can improve the diagnostic accuracy in suspected PE patients in the emergency department. Methods A prospective observational study of 112 consecutive adult patients suspected of PE of whom 102 were eligible for analysis. ADSF was calculated using arterial carbon dioxide and end-tidal carbon dioxide. An ADSF less than 0.2 was considered normal. Results PE was confirmed in 11 (10.8%) of 102 patients. D-dimer assay alone as a reference standard test for PE had a sensitivity of 100%, specificity of 38.5% and false negativity of 0%. Area under the receiver-operator characteristic curve for the diagnosis of PE using ADSF values alone was 0.894, Sensitivity, specificity and false negativity for the combined results of a positive D-dimer test and abnormal ADSF were 100%, 78.0% and 0% for the presence of PE, respectively. Of 65 patients with a low or intermediate clinical probability and a positive D-dimer assay, 36 (55.4%) patients displayed normal ADSF and had no PE. Conclusions By itself ADSF assessment performed well in diagnosis of PE. The combined result of a positive D-dimer and abnormal ADSF increased the specificity for diagnosing PE compared with the D-dimer test alone. The use of additional bedside ADSF assessment following a positive D-dimer test may reduce the need for further imaging studies to detect PE in patients with a low or intermediate clinical probability.

Anticholinesterase therapy for patients with ophthalmoplegia following snake bites: Report of two cases

Although ophthalmoplegia following snake bites is not indicative of a serious neurotoxic complication, symptoms of diplopia, dizziness and ocular discomfort can be emotionally devastating for patients. The authors experienced two cases of ophthalmoplegia following snake bites in Korea. The patients complained of diplopia that had developed several hours after the snake bites. The diplopia did not improve with antivenom treatment, but resolved completely after several injections of neostigmine.

Effect of hypertonic saline on apoptosis of polymorphonuclear cells

BACKGROUND The function of polymorphonuclear (PMN) cells can be influenced by the choice of resuscitation fluids in hemorrhagic shock. Widespread interest in the use of hypertonic solutions for resuscitation has led to extensive investigation of their immune-modulating properties. Hypertonic saline (HTS) is known to modulate immune reactions, preventing the multiorgan failure mediated by immune reactions in trauma and hemorrhagic shock. PMN cells play a key role in such immune-mediated inflammatory processes, and HTS is believed to affect these PMN cells. However, how these events influence the actual event of apoptosis has not yet been described. Thus, in the present study, we aimed to investigate the differences in the apoptosis of PMN cells when exposed to isotonic and hypertonic environments and the temporal relations between the interval of administration of HTS after the stimulation of PMN cells. METHODS Whole blood was sampled from healthy volunteers, and the PMN cells were isolated. The isolated layer of PMN cells was washed twice with phosphate-buffered saline to yield the PMN cells. The number of cells was kept uniform, and an overall survival rate greater than 95% was maintained. After stimulation of the isolated PMN cells with N-formyl-methionyl-leucyl-phenylalanine, the PMN cells were allocated into 3 study groups (i.e., 1 isotonic group and 2 hypertonic groups with an osmolarity of 160 mM and 180 mM each). The extent of apoptosis was investigated in each group after culturing the PMN cells for 0, 1, 3, 6, 12, 15, 18, and 24 h. Depending on whether the PMN cells were stimulated with N-formyl-methionyl-leucyl-phenylalanine, they were also divided into stimulated and nonstimulated groups. In the stimulated group, the hypertonic environment was fostered immediately (HTS 0 h) and 6 h (HTS 6 h) after stimulation, which was accomplished after allocating the cells into an isotonic group (140 mM) and a hypertonic group (180 mM), according to the concentration of the culture medium. The PMN cells were then cultured at 37°C for 15 h with 5% carbon dioxide incubation. Each PMN suspension was labeled with Annexin V-fluorescein isothiocyanate and propidium iodide. Each sample underwent immediate flow cytometric analysis. PMN cells with high propidium iodide uptake were considered nonviable (necrotic). Among the viable PMN cells, those with no Annexin V uptake were considered normal and those with Annexin V uptake were considered apoptotic. RESULTS Decreased apoptosis was observed in the PMN cells stimulated with N-formyl-methionyl-leucyl-phenylalanine. Increased apoptosis was observed in the stimulated PMN cells incubated in hypertonic condition compared with the cells incubated in isotonic condition. Early HTS administration demonstrated increased apoptosis compared with late administration. CONCLUSIONS HTS treatment resulted in increased PMN apoptosis and an anti-inflammatory effect. Decreased apoptosis (prolonged lifespan) has been implicated in neutrophil-mediated tissue damage. HTS, by increasing the apoptosis of PMN cells, attenuates the postinjury inflammatory response. Also, early treatment with HTS was more efficient than delayed treatment.

Reversible pancytopenia following the consumption of decoction of Ganoderma neojaponicum Imazeki

The Ganoderma species are mushrooms used for herbal medicinal purposes in northeast Asia. Two cases of simultaneous reversible pancytopenia following the consumption of decoction of Ganoderma neojaponicum Imazeki are presented. Other than decoction of G. neojaponicum Imazeki no cause of pancytopenia could be identified. The patients recovered fully after conservative treatment. People who consume herbal medicines are often not aware of their side effects. Patients should be knowledgeable regarding the possible side effects of Ganoderma prior to its consumption.

Clinician awareness of tetanus-diphtheria vaccination in trauma patients: a questionnaire study

BackgroundMost trauma patients visit the hospital via the emergency department. They are at high risk for tetanus infection because many trauma patients are wounded. Tetanus immunity in the Korean population has been revealed to be decreased in age groups over 20 years old. It is important for emergency physicians to vaccinate patients with the tetanus booster in wound management.MethodsQuestionnaires were sent to the directors of the emergency departments of resident training hospitals certified by the Korean Society of Emergency Medicine.ResultsTwo thirds of the emergency department directors surveyed reported applying tetanus prophylaxis guidelines to more than 80% of wounded patients. However, about 45% of clinicians in the emergency departments considered giving less than half of the wounded patient tetanus booster vaccinations, and there were no distinct differences in tetanus booster vaccination rates among different age groups. Most emergency physicians are familiar with tetanus prophylaxis guidelines for wound management. However, more than half of the emergency department directors reported that the major reason for not considering tetanus-diphtheria vaccination was due to assumptions that patients already had tetanus immunity.ConclusionAttitude changes should be encouraged among emergency physicians regarding tetanus prophylaxis. As emergency physicians are frequently confronted with patients that are at a high risk for tetanus infection in emergency situations, they need to be more informed regarding tetanus immunity epidemiology and encouraged to administer tetanus booster vaccines.

Effect of hypertonic saline and macrophage migration inhibitory factor in restoration of T cell dysfunction

Purpose Trauma-induced suppression of cellular immune function likely contributes to sepsis, multiple organ dysfunction syndrome and death. T cell proliferation decreases after traumatic stress. The addition of prostaglandin E2 (PGE2), which depresses immune function after hemorrhage and trauma, to T-cells decreases T-cell proliferation; and hypertonic saline restores PGE2-induced T-cell suppression. Recently, it has become apparent that macrophage migration inhibitory factor (MIF) plays a central role in several immune responses, including T-cell proliferation. However, the role of MIF in mediating hypertonic saline (HTS) restoration of T cell dysfunction is unknown. Therefore, we hypothesize that T cell immune restoration by HTS occurs, at least in part, by a MIF-mediated mechanism. Methods Jurkat cells were cultured in Roswell Park Memorial Institute media, at a final concentration of 2.5 × 106 cell/mL. The effects of HTS on T-cell proliferation following PGE2-induced suppression were evaluated in Jurkat cells: HTS at 20 or 40 mmol/L above isotonicity was added. MIF levels were determined by enzyme-linked immunosorbent assay and western blot analysis. Results PGE2 caused a 15.0% inhibition of Jurkat cell proliferation, as compared to the control. MIF levels decreased in PGE2-suppressed cells, as compared to the control. MIF levels were higher in cells treated with HTS than PGE2-stimulated cells. Conclusion The role of HTS in restoring Jurkat cells proliferation suppressed by PGE2, at least in part, should be mediated through a MIF pathway.

Korean Shock Society septic shock registry: a preliminary report

Objective To evaluate the clinical characteristics, therapeutic interventions, and outcomes of patients with septic shock admitted to the emergency department (ED). Methods This study was a preliminary, descriptive analysis of a prospective, multi-center, observational registry of the EDs of 10 hospitals participating in the Korean Shock Society. Patients aged 19 years or older who had a suspected or confirmed infection and evidence of refractory hypotension or hypoperfusion were included. Results A total of 468 patients were enrolled (median age, 71.3 years; male, 55.1%; refractory hypotension, 82.9%; hyperlactatemia without hypotension, 17.1%). Respiratory infection was the most common source of infection (31.0%). The median Sepsis-related Organ Failure Assessment score was 7.5. The sepsis bundle compliance was 91.2% for lactate measurement, 70.3% for blood culture, 68.4% for antibiotic administration, 80.3% for fluid resuscitation, 97.8% for vasopressor application, 68.0% for central venous pressure measurement, 22.0% for central venous oxygen saturation measurement, and 59.2% for repeated lactate measurement. Among patients who underwent interventions for source control (n=117, 25.1%), 43 (36.8%) received interventions within 12 hours of ED arrival. The in-hospital, 28-day, and 90-day mortality rates were 22.9%, 21.8%, and 27.1%, respectively. The median ED and hospital lengths of stay were 6.8 hours and 12 days, respectively. Conclusion This preliminary report revealed a mortality of over 20% in patients with septic shock, which suggests that there are areas for improvement in terms of the quality of initial resuscitation and outcomes of septic shock patients in the ED.

Accuracy of transcutaneous carbon dioxide monitoring in hypotensive patients

Objectives Continuous blood gas monitoring is frequently necessary in critically ill patients. Our aim was to assess the accuracy of transcutaneous CO2 tension (PtcCO2) monitoring in the emergency department (ED) assessment of hypotensive patients by comparing it with the gold standard of arterial blood gas analysis (ABGA). Methods All patients receiving PtcCO2 monitoring in the ED were included. We excluded paediatric patients, patients with no ABGA results during a hypotensive event, patients whose ABGA was not performed simultaneously with PtcCO2 monitoring, and patients who received sodium bicarbonate for resuscitation. The included patients were classified into hypotensive patients and normotensive patients. A hypotensive patient was defined as a patient showing a mean arterial pressure under 60 mm Hg. The agreement in measurement between PaCO2 tension (PaCO2) and PtcCO2 were investigated in both groups. Results The mean difference between PaCO2 and PtcCO2 was 2.1 mm Hg, and the Bland–Altman limits of agreement (bias±1.96 SD) ranged from −15.6 to 19.7 mm Hg in the 28 normotensive patients. The mean difference between PaCO2 and PtcCO2 was 1.1 mm Hg, and the Bland–Altman limits of agreement (bias±1.96 SD) ranged from −19.5 to 21.7 mm Hg in the 26 hypotensive patients. The weighted κ values were 0.64 in the normotensive patients and 0.60 in the hypotensive patients. Conclusions PtcCO2 monitoring showed wider limits of agreement with PaCO2 in urgent situations in the ED environment. However, acutely developed hypotension does not affect the accuracy of PtcCO2 monitoring.

The Effect of Hypertonic Saline on mRNA of Proinflammatory Cytokines in Lipopolysaccharide-Stimulated Polymorphonuclear Cells

Background Hypertonic saline is often used to resuscitate patients experiencing shock. In such conditions, polymorphonuclear cells and Toll-like receptors (TLRs) form an essential part of early induced innate immunity. Objective To investigate the immunomodulatory effect of hypertonic saline on polymorphonuclear cells by evaluating the changes in TLR-4 receptors and proinflammatory cytokines. Methods Polymorphonuclear cells were isolated from whole blood using Polymorphprep (Axis-Shield, Oslo, Norway). The isolated polymorphonuclear cells were plated at a density of 1 × 106 cells/mL in 6-well flat-bottomed culture plates and were stimulated with 1 μg/mL lipopolysaccharide or N-formyl-methionyl-leucyl-phenylalanine. The stimulated polymorphonuclear cells were cultured in hypertonic saline at 10, 20, or 40 mmol/L above isotonicity. After that, the changes in TLR-4 and cytokines were measured by quantitative real-time polymerase chain reaction and flow cytometry. Results The level of TLR-4 mRNA expression decreased after stimulation with N-formyl-methionyl-leucyl-phenylalanine, but hypertonic saline did not affect the TLR-4 mRNA expression. TLR-4 mRNA expression was clearly induced upon stimulation with lipopolysaccharide, and the addition of hypertonic saline restored TLR-4 mRNA expression in polymorphonuclear cells. The interleukin-1β mRNA expression was decreased in the hypertonic environment. On the other hand, the tumor necrosis factor-α value was not influenced by the addition of hypertonic saline. Conclusions Hypertonic saline has an immunomodulatory effect on polymorphonuclear cells through the TLR-4 pathway, and the interleukin–1β-associated pathway is influenced more by hypertonic saline than is the tumor necrosis factor–α-associated pathway.