Young Duck Cho

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.

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.

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.

Hypertonic saline downregulate the production level of lipopolysaccharide-induced migration inhibitory factor in THP-1 cells

Purpose Macrophage migration inhibitory factor (MIF) may serve as a general marker for systemic inflammation in septic and nonseptic acute critical illness. Additionally, our previous experiment has demonstrated that immunosuppressant Prostaglandin E2 (PGE2) lowered MIF levels and inhibited T-cells proliferation when compared to control levels. The addition of hypertonic saline (HTS) increased MIF production as compared with PGE2-stimulated T-cells in concordance with restore PGE2-suppressed T-cells proliferation. Generally, HTS has been well known for its anti-inflammatory effect so far. Therefore, the experiments were conducted to evaluate MIF after stimulating lipopolysaccharide (LPS) either in the presence or absence of HTS in monocyte, in response to early phase injury. Methods Human acute monocytic leukemic cell line (THP-1) cells were cultured in RPMI media, to a final concentration of 1 × 106 cells/mL. The effect of HTS on LPS-induced MIF was evaluated in monocyte with 1 µg/mL LPS. HTS at 10, 20 or 40 mmol/L above isotonicity was added. MIF concentrations of the supernatant were determined by enzyme-linked immunosorbent assay, and cell lysates were used for Western blots analysis to determine the MIF expression. Results MIF concentrations in the cell supernatant increased in LPS-induced cells compared to control cells. Also, levels of MIF protein expression were higher in LPS stimulating cells. However, the addition of HTS to LPS stimulated cell restored MIF concentrations and MIF expression. Conclusion The role of HTS in maintaining physiological balance in human beings, at least in part, should be mediated through the MIF pathway.

Macrophage migration inhibitory factor levels correlate with an infection in trauma patients

BACKGROUND The role of migration inhibitory factor (MIF) is best understood in septic shock and septic disease; however, the role of MIF in a secondary infection after trauma has not yet been completely studied. This study aimed to evaluate the role of MIF in trauma patients. METHODS The patients in the study population were divided into two groups according to the results of their MIF levels. The initial MIF levels, trauma mechanism, revised trauma score, survival rate, length of stay (LOS) in the intensive care unit (ICU), level of leukocytes, and level of C-reactive protein (CRP) were compared between the groups. RESULTS Overall, 116 patients were enrolled from August 1, 2014 to July 31, 2015. LOS in ICU in the elevated MIF group was 5.67±7.54 days compared with 2.09±2.26 days in the normal MIF group. Further, CRP level in the elevated MIF group was higher than that in the normal MIF group. CONCLUSION In a place such as the department of emergency medicine, it is critical and important for emergency physicians to make a proper judgment and to prepare for the worst scenario. Therefore, the utilization of MIF level in trauma patients has a possibility for assisting emergency physicians.

Radiation exposure from computed tomography in blunt trauma patients

Background: As the use of CT increases, it has raised the question for the radiation induced adverse effect. The management of blunt trauma has been influenced by the advance in the technology of CT. CT makes it possible to characterize the multiple injured patient and establish the priorities of management with more precise information. With the liberal use of CT for blunt trauma, whole body CT scanning, the-so called panscan, has often been used in trauma center to detect possible missed injuries. Within the Organization of Economic Cooperation Development (OECD) countries, South Korea has the third largest number of CT scanners per million people after Japan and Australasia. The annual number of CT examination is increasing every year. The object of this study was to assess the radiation exposure from computed tomography in multiple blunt trauma patients. Methods: This study was a retrospective cross sectional study performed for multiple blunt trauma patients visiting the OOOO Emergency Department during one year. Using data from our Hospital information system, we selected patients provided with trauma code of Korean Standard Classification of Diseases and three or more types of computed tomography at the same time in ED. The data collected by patients chart review were age, sex, initial vital signs, Glasgow coma scale (GCS), final diagnosis, injury severity score (ISS), cause of injury, mode of transportation, body location of injury, dispatch route from ED, received types CT, and the reading of CT by radiologist. Each CT conducted to patients was categorized into CT related to final diagnosis or CT unrelated to final diagnosis. Dose length product (DLP) depending on the type of CT was also examined by review of Picture Archiving and Communication System (PACS) in each patient. Total number of initial CT conducted to patients and average estimated effective dose depending type of CT were investigated. Estimated effective dose was calculated as DLP multiplied by a“ k”conversion factor. The reference for conversion factor was AAPM reports NO. 96. (9) Characteristics of CT and average effective dose unrelated to final diagnosis were also analyzed. Finally, we tried to find the factor affecting estimated effective dose. Results: 1. Clinical data of include patients and Injury details of patients. Total 110 patients were searched on the database of hospital information system during a study period. The included patients received radiographic evaluation using 16-slice CT scanner (SOMATOM Sensation 16, Siemens, Forchheim, Germany). Clinical data of included patients are shown in table 1. About one third of the patients had initial GCS score under 14 and 60 percentage of patients had ISS score under 15. The most common causes of injury were fall and motor crash injury. They occupied near half of all cause. Almost patients visited emergency department by emergency medical service (EMS) and only 13 patients visited ED via other than EMS. Head and limb were the major body location of injury. Dispatch route from ED were transferred, intensive unit, general ward, discharged home, operation and died in the order of frequency. 2. The characteristics of initial computed tomography (CT) conducted to patients. The 105 patients received total 408 CT scans initially. The main conducted types of CT were head, chest and abdomen. Estimated effective dose depending on type of CT did not differ from the levels of radiation exposure ever known. No. of patients receiving estimated effect dose over 20 mSv is 59(56.2%). About 60 percentages of total CT examinations was not associated with the final diagnosis. The patients received 2.35±1.26 (mean± standard deviation) CT scans unrelated to final diagnosis. Accordingly, average estimated effective dose due to CT unrelated to final diagnosis was 12.80±8.54 (mean±standard deviation) mSv. 3. The factors affecting the estimated effective dose. Estimated effective dose according to the sex, age, GCS, ISS, dispatched route and cause of injury was investigated. The mean values of total estimated effective dose were not different in subgroup of variables. The mean values of estimated effective dose unrelated final diagnosis were also not different in all subgroup of variables except ISS. The patients with ISS<15 received higher estimated effective dose unrelated final diagnosis than with ISS≥15. Conclusion: Considerable number of CT scans was unrelated to patient final diagnosis. Although CT scan is essential to evaluate in blunt trauma patients, emergency physicians should understand the radiologic risk from multiple CT scan and consider it when evaluating trauma patient.

Heart rate variability measurement in sepsis patients

Objectives Inflammation makes an influence on autonomic nervous system and a change in autonomic nervous activity affects heart rate. Heart rate variability (HRV) test can quantify the autonomous nervous activity. In this study, we evaluated the meaning of heart rate variability in sepsis patients. Methods Heart rate variability test was performed for sepsis patients and healthy volunteers. Normalised low frequency power, reflecting sympathetic activity, was compared to acute physiology and chronic health evaluation II (APACHE II) score and mortality in emergency department sepsis (MEDS) score in sepsis patients. Then the patients were divided into four groups: 1) severe sepsis patients, 2) sepsis patients admitted to general ward, 3) sepsis patients discharged within 24 hours and 4) healthy volunteers. We obtained averages for the HRV results in all four groups. The receiver operating characteristics curve was examined to determine whether or not HRV variables could be used to triage sepsis patients. Results Correlations between normalised low frequency power (LFnu) with APACHE II score and MEDS score were −0.595 and −0.514, respectively. Low frequency power (LF) and LFnu values decreased in sepsis patients with the higher scores observed in the discharged sepsis patients and healthy volunteers. The areas under the curve for the values of LF and LFnu in the admission and discharge groups were 0.746 and 0.635, respectively (p<0.05). Conclusion Variables related to heart rate variability are significantly correlated with the severity of sepsis patients. Although the HRV test alone cannot accurately predict the disposition of sepsis patients, in the emergency room setting it helps to assign beds to sepsis patients within the triage system, and avoid over-population. (Hong Kong j.emerg.med. 2014;21:73-79)

Acute hepatitis and acute kidney insufficiency caused by ingestion of raw grass carp gall bladder.

Dear Editor, A 25-year-old male patient entered the emergency room (ER) with complaints of vomiting and numerous watery diarrhoeas. After consuming raw grass carp bile, he developed abdominal cramps with repeated vomiting and watery diarrhoea for 36 h. At his arrival at the ER, he was acutely ill looking and vital signs were as follows: blood pressure, 122/69 mmHg; pulse rate, 69/min; respiration rate, 20 breaths per minute; and body temperature, 37.2°C. On physical examination, abdomen was soft and not distended. He did not have any medical history and was not on any kind of medication. Bowel sound was hyperactive and mild tenderness was noted around the lower abdomen area. He was suspicious of acute food poisoning and blood and stool samples were ordered. Laboratory tests revealed serum aspartate aminotransferase (AST) of 7836 (10–44) IU/L and alanine transferase (ALT) of 7479 (10–44) IU/L, total bilirubin of 3.01 (0.2–1.2) mg/dL, direct bilirubin of 1.98 (0–0.4) mg/dL, total bilirubin 2.0 (0.2–1.2) mg/dL, prothrombin time (15.3 s, 75%, INR 1.21), blood urea nitrogen (BUN) of 32.0 (7–20) mg/dL, serum creatinine of 2.33 (0.6–1.3) mg/dL, and urinalysis revealed no signs of proteinuria or albuminuria. Plain radiography was normal. Serology for hepatitis was negative and no other hepatotoxin was identified. Ultrasonography revealed a mildly coarse parenchymal echogenicity with no evidence of liver cirrhosis and ascite and mild cortical echogenicity increase of both kidneys. His stool and blood sample for culture came back negative. He was admitted under impressions of acute toxic hepatitis and acute kidney insufficiency. During admission he was treated conservatively and a series of laboratory tests were ordered. AST and ALT were normalised in 6 days and BUN and creatinine were normalised in 5 days. He was discharged in 11 days and returned to daily life. In some countries of Asia, fish gall bladder and carp bile were handed down by oral tradition as a remedy for hypertension and detoxification and favoured as a herbal tonic. However, its use as medicine is not scientifically proven and some cases of toxicity of raw carp gall bladder have been reported. Clinical symptoms after ingestion of raw fish bile are non-specific as general weakness, anorexia, cramping abdominal pain, nausea and vomiting. Also, oliguria and oedema are noted as signs of acute kidney insufficiency. Symptoms vary from gastroenteritis from mild intoxication to moderate intoxication involving the kidney and liver, to severe intoxication causing multi-organ failure. Two studies had revealed that 5a-cyprinol and 5a-cyprinol sulfate from grass carp bile could be responsible for acute kidney insufficiency and toxic hepatitis. In an in vivo study, raw carp bile caused multiple focal necrosis in the liver and renal oedema in rat; however, a clear mechanism has not been identified yet. Although deaths have been reported in some severe cases, most patients recovered without complications and conservative treatment was sufficient. There were some cases of raw carp bile-induced acute hepatitis and renal insufficiency in a few countries; however, since the year 2008, no case of ingestion of raw carp bile has been reported in South Korea. Despite the widespread use of basic public health food safety and hygiene measures, it is surprising that some people still believe that ingestion of raw carp bile can improve health. An aspect of this case that caught our attention was the recurrence of complication of herbal or traditional medicine. With efforts from public healthcare and education, the reckless trial of unproven traditional herbal medicine seemed to decrease in our society. Only seven case reports for raw carp bile-induced complication were found in PubMed. In the United States, there were only two cases of acute hepatitis and renal failure following ingestion of raw carp gall bladder and they were immigrants from South Korea and Cambodia. As we can see from the two cases reported in the United States, immigrants from developing countries might influence the rate of diminishing cases of intoxication from consuming herbal medicine. Therefore, we need to be more alert and cautious. The trend in increase of intoxication incidences needs to be studied further with more data.