Real World Characteristics and Clinical Outcomes of HER2-Mutant Non–Small Cell Lung Cancer Patients Detected by Next-Generation Sequencing / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study was conducted to investigate the clinical characteristics of patients with advanced non–small cell lung cancer (NSCLC) harboring human epidermal growth factor receptor 2 (HER2) mutations and to evaluate response to standard treatment and HER2-targeted agents. @*Materials and Methods@#Using tissue and/or blood next-generation sequencing, we identified 44 patients with NSCLC harboring HER2 mutations who were treated at Severance Hospital between December 2016 and February 2021. Clinical data, including patient characteristics, mutation status, incidence of metastasis for distant lesions, and response to chemotherapy, were retrospectively analyzed. @*Results@#The median age was 58 years, and 61% of the patients were female. Most patients (64%) were never-smokers. Adenocarcinoma was the most predominant subtype (98%). A total of 66% of the patients had extrathoracic metastatic lesions, and 32% had intracranial lesions at initial presentation. The median time to the development of brain metastasis was 15.6 months (range, 2.4 to 43.7). The most common type of HER2 mutation was 12 base pair in-frame insertion in exon 20, A775_G776insYVMA. Of the 44 patients, two had concomitant driver mutations, one with epidermal growth factor receptor (EGFR) mutation (V769M), and one with BRAF mutation (V600E). Patients treated with pemetrexed-based chemotherapy (75%) had an overall response rate (ORR) and progression-free survival (PFS) of 30% and 8.3 months (95% confidence interval [CI], 3.9 to 12.7), respectively. The ORR and PFS of HER2-targeted agent treated patients (14%) were 0.0% and 1.9 months (95% CI, 0.1 to 2.8), respectively. @*Conclusion@#Given its distinct characteristics and treatment responses, novel treatment strategies for HER2-mutant NSCLC should be developed promptly to improve survival outcomes of patients.

The Effects of Preoperative Aspirin on Coronary Artery Bypass Surgery: a Systematic Meta-Analysis

BACKGROUND AND OBJECTIVES: Aspirin plays an important role in the maintenance of graft patency and the prevention of thrombotic event after coronary artery bypass graft surgery (CABG). However, the use of preoperative aspirin is still under debate due to the risk of bleeding. METHODS: From PubMed, EMBASE, and Cochrane Central Register of Controlled Trials, data were extracted by 2 independent reviewers. Meta-analysis using random effect model was performed. RESULTS: We performed a systemic meta-analysis of 17 studies (12 randomized controlled studies and 5 non-randomized registries) which compared clinical outcomes of 9,101 patients who underwent CABG with or without preoperative aspirin administration. Preoperative aspirin increased chest tube drainage (weighted mean difference 177.4 mL, 95% confidence interval [CI], 41.3–313.4; p=0.011). However, the risk of re-operation for bleeding was not different between the preoperative aspirin group and the control group (3.2% vs. 2.4%; odds ratio [OR], 1.23; 95% CI, 0.94–1.60; p=0.102). There was no difference in the rates of all-cause mortality (1.6% vs. 1.5%; OR, 0.98; 95% CI, 0.64–1.49; p=0.920) and myocardial infarction (MI) (8.7% vs. 10.4%; OR, 0.83; 95% CI, 0.66–1.04; p=0.102) between patients with and without preoperative aspirin administration. CONCLUSIONS: Although aspirin increased the amount of chest tube drainage, it was not associated with increased risk of re-operation for bleeding. In addition, the risks of early postoperative all-cause mortality and MI were not reduced by using preoperative aspirin.

Real-World Analysis of the Efficacy of Rebiopsy and EGFR Mutation Test of Tissue and Plasma Samples in Drug-Resistant Non-Small Cell Lung Cancer

PURPOSE: Standard treatment for cases of non-small cell lung cancer (NSCLC) exhibiting acquired drug resistance includes tumor rebiopsy, epidermal growth factor receptor (EGFR) mutation testing (e.g., for T790M mutations), and the subsequent administration of third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, rebiopsies are typically invasive, costly, and occasionally not feasible. Therefore, the present study aimed to assess rebiopsy procedures by analyzing real-world data collected by the ASTRIS study of patients with resistant NSCLC. MATERIALS AND METHODS: The present study used statistical models to evaluate data collected by the ASTRIS trial (NCT02474355) conducted at Yonsei Cancer Center, including the rebiopsy success rate, incidence of T790M mutations in collected tissue and plasma samples, and association of administered osimertinib treatment efficacy. RESULTS: In a total of 188 screened patients, 112 underwent rebiopsy. An adequate tumor specimen was obtained in 95 of these patients, the greatest majority of whom (43.8%) were subjected to bronchoscopy. T790M mutations were detected in 53.3% of successfully EGFR-tested rebiopsy samples. A total of 88 patients received osimertinib treatment, and the objective response rate and median progression-free survival time was 44.3% and 32.7 weeks, respectively, among the treated patients overall, but 57.8% and 45.0 weeks, and 35.2% and 20.4 weeks among patients who exhibited T790M-positive tissue (n=45) and plasma (n=54) samples, respectively. CONCLUSION: Approximately 60% of patients in the analyzed real-world cohort were eligible for tissue rebiopsy upon NSCLC progression. Osimertinib activity was higher in patients in whom T790M mutations were detected in tissues rather than in plasma samples.

The Effects of Preoperative Aspirin on Coronary Artery Bypass Surgery: a Systematic Meta-Analysis

BACKGROUND AND OBJECTIVES@#Aspirin plays an important role in the maintenance of graft patency and the prevention of thrombotic event after coronary artery bypass graft surgery (CABG). However, the use of preoperative aspirin is still under debate due to the risk of bleeding.@*METHODS@#From PubMed, EMBASE, and Cochrane Central Register of Controlled Trials, data were extracted by 2 independent reviewers. Meta-analysis using random effect model was performed.@*RESULTS@#We performed a systemic meta-analysis of 17 studies (12 randomized controlled studies and 5 non-randomized registries) which compared clinical outcomes of 9,101 patients who underwent CABG with or without preoperative aspirin administration. Preoperative aspirin increased chest tube drainage (weighted mean difference 177.4 mL, 95% confidence interval [CI], 41.3–313.4; p=0.011). However, the risk of re-operation for bleeding was not different between the preoperative aspirin group and the control group (3.2% vs. 2.4%; odds ratio [OR], 1.23; 95% CI, 0.94–1.60; p=0.102). There was no difference in the rates of all-cause mortality (1.6% vs. 1.5%; OR, 0.98; 95% CI, 0.64–1.49; p=0.920) and myocardial infarction (MI) (8.7% vs. 10.4%; OR, 0.83; 95% CI, 0.66–1.04; p=0.102) between patients with and without preoperative aspirin administration.@*CONCLUSIONS@#Although aspirin increased the amount of chest tube drainage, it was not associated with increased risk of re-operation for bleeding. In addition, the risks of early postoperative all-cause mortality and MI were not reduced by using preoperative aspirin.

Emphysema prevalence related air pollution caused by a cement plant

BACKGROUND: To identify adverse pulmonary health effects due to air pollution derived from a cement plant in Korea. The emphysema prevalence in residents around a cement plant was compared to that in the group who live far away from the plant by chest films (PA and lateral view) and high-resolution computed tomography (HRCT) lung images. METHODS: From June to August in 2013 and from August to November in 2014, chest films and HRCT scan were conducted on residents over the age of 40 who lived around a cement plant. The residents were divided into two groups; a “more exposed group (MEG)” which consisted of 1,046 people who lived within a 1 km radius and a “less exposed group (LEG)” which consisted of 317 people who lived more than 5 km away from the same plant. We compared the emphysema prevalence and estimated the OR of this between the MEG and the LEG by using a chi-square and logistic regression on chest films and HRCT. RESULTS: The emphysema prevalence was 9.1 % in the LEG, 14.3 % in the MEG on chest films and 11.4 %, 17.8 % on the HRCT, respectively. The OR of the emphysema prevalence in MEG was 2.92 (95 % CI 1.77-4.83) on the chest films, 2.56 (95 % CI 1.64–3.99) on the HRCT after sex, age, body mass index (BMI), smoking history, residency period and firewood used history were adjusted. The OR in the less than 29 pack-years smoking history was 1.66 (95 % CI 0.92–3.06) and in the more than 30 pack-years was 3.05 (95 % CI 1.68–5.52) on the chest films, and was 1.68 (95 % CI 0.98–2.90), 2.93 (95 % CI 1.72–4.98) on the HRCT, respectively. CONCLUSION: The emphysema prevalence seems to be affected by the level of exposure to air pollution derived from the cement plant as well as sex, age, BMI, and smoking history in this study. Moreover, the OR of the case of the more exposed to the air pollution was similar to that of the case in smoking.

Ventilation impairment of residents around a cement plant

OBJECTIVES: To identify adverse health effects due to air pollution derived from a cement plant in Korea. The ventilation impairment in residents around a cement plant was compared to another group through a pulmonary function test (PFT). METHODS: From June to August of 2013, both a pre and post-bronchodilator PFT was conducted on a "more exposed group (MEG)" which consisted of 318 people who lived within a 1 km radius of a cement plant and a "less exposed group (LEG)" which consisted of 129 people who lived more than 5 km away from the same plant. The largest forced expiratory volume in a one second (FEV1) reading and a functional residual capacity (FVC) reading were recorded after examining the data from all of the usable curves that were agreed upon as valid by PFT experts of committee of National Institute of Environmental Research. The global initiative for chronic obstructive lung disease (GOLD) criteria for COPD, defined the FEV1/FVC ratio == 0.7 and FVC% predicted < 80% were as the restrictive type. The FVC% predicted value was estimated using Korean equation. We compared the proportion of lung function impairments between the MEG and the LEG by using a chi-square, and estimated the OR of obstructive and restrictive ventilation impairments by logistic regression. RESULTS: The obstructive type impairment proportion was 9.7% in the MEG, whereas it was 8.5% in the LEG. The restrictive type was 21.6% in the MEG which was more than the 12.4% of the LEG. The odds ratio (OR) of total ventilation impairment in the MEG was 2.63 (95% CI 1.50 ~ 4.61) compared to the LEG. The OR of obstructive type in the MEG was 1.60 (95% CI 0.70 ~ 3.65), the smoking history was 3.10 (CI 1.10 ~ 8.66) whereas OR of restrictive type in the MEG was 2.55 (95% CI 1.37 ~ 4.76), the smoking history was 0.75 (95% CI 0.35 ~ 1.60) after adjusting for sex and age. Level of exposure to particulate played a role in both types. However, it appeared to be a significant variable in restrictive type, while smoking history was also an important variable in obstructive type. CONCLUSION: Although this study is a limited cross-section study with a small number of subjects, ventilation impairment rate is higher in the MEG. There might be a possibility that it is due to long-term exposure to particulate dust generated by the cement plant.

Variability of Offending Allergens of Allergic Rhinitis According to Age: Optimization of Skin Prick Test Allergens

PURPOSE: This study evaluates offending allergens in patients with allergic rhinitis (AR) according to age that establish a minimal panel for skin prick test (SPT) allergens required to identify if a patient is sensitized. METHODS: We retrospectively analyzed SPT results according to age to determine the minimum test battery panel necessary to screen at least 93%-95% of AR patients. Allergic skin tests (common airborne indoor and outdoor allergens) were performed on 7,182 patients from January 2007 to June 2011. All patients were classified into 9 groups according to age; subsequently, we investigated offending allergens by age group. RESULTS: A total of 5,032 (70.1%) patients were found sensitized to at least one of the 55 aeroallergen extracts tested. The annual ranking of offending allergens was not significantly different from each other over the past 5 years. House dust mites (HDM) were the most prevalent allergens ranked from first to third for all 5 years. The allergens in the minimum test panel differed slightly among all age groups; in addition, the types of sensitized allergen sources were more diverse in the older versus younger age group. HDM covered a larger proportion of the sensitized allergens in the younger age group versus the older age group. Testing with 5 allergens (Dermatophagoides farinae, Tetranychus urticae, oak, mugwort and cockroach) adequately identified over 90% of the sensitized patients. CONCLUSIONS: A SPT with around 5-7 allergens adequately detected most of the sensitization in the majority of the age groups in Korea. However, this study suggests that physicians perform the SPT with appropriately selected allergens in each age category for the screening of AR.

Lipid Profiles and Prevalence of Dyslipidemia in Korean Adolescents

BACKGROUND: The aim of this study is to investigate the distribution of plasma cholesterol and triglyceride levels as well as the prevalence of dyslipidemia among Korean adolescents. METHODS: We analyzed data for 3,045 adolescents aged 10-18 years (1,622 boys and 1,423 girls) who participated in the Korea National Health and Nutrition Examination Surveys from 2007 to 2010. RESULTS: The mean values of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were 159, 89, 89, and 52 mg/dL, respectively. Plasma cholesterol levels were significantly higher in girls than those in boys (162.1 mg/dL vs. 155.6 mg/dL, P < 0.0001). The 90th percentile values of total cholesterol, triglycerides, and LDL-C were 192, 149, 117 mg/dL for boys, and 195, 147, 119 mg/dL for girls. The 10th percentile value of HDL-C was 38 mg/dL for boys and 40 mg/dL for girls. Triglyceride, LDL-C cholesterol levels increased, whereas plasma HDL-C levels decreased with increasing the body mass index (P < 0.0001) in both genders. Total cholesterol levels significantly increased with increasing the body mass index, especially in boys (P < 0.0001). The prevalence of dyslipidemia was 25.2% for boys and 21.7% for girls; this value significantly increased with overweight (37-40%) and obesity (53-56%). Independent predictors (odds ratio) of dyslipidemia were age (1.49), overweight (2.06), and obesity (5.11) for boys; overweight (1.95) and obesity (3.22) for girls. CONCLUSION: Adolescent dyslipidemia is strongly associated with obesity. Lipid screening for overweight or obese youths should be emphasized. Further, longitudinal studies examining the impact of childhood obesity and dyslipidemia on subsequent cardiovascular diseases are needed.

Dietary patterns and metabolic syndrome risk factors among adolescents / 소아과

PURPOSE: Unbalanced diets and decreased physical activity have contributed to increased prevalence of obesity and metabolic syndrome in adolescents. We have performed a systematic review and data analysis to examine the association between dietary pattern and metabolic syndrome risk factors in adolescents. METHODS: We searched the PubMed and BioMedLib databases for appropriate articles published during the past 10 years and selected 6 articles. The studies reviewed applied factor analysis or cluster analysis to extract dietary patterns. For data analysis, we examined the association between dietary patterns and the prevalence of metabolic syndrome risk factors using data of 3,168 adolescents (13 to 18 years) obtained from 4 consecutive Korean Nutrition Health and Nutrition Examination Surveys (1998, 2001, 2005, and 2007 to 2009). RESULTS: Our systematic review confirmed that western dietary patterns are positively associated with metabolic syndrome risk factors such as obesity and elevated triglycerides, while traditional dietary patterns were negatively associated. Data analysis found that the number of adolescents aged 16 to 18 years who had "Rice & Kimchi" dietary pattern decreased, while the number having western dietary patterns increased during the 1998 to 2009 time frame. There were no changes in the dietary patterns in adolescents aged 13 to 15 years. The risk of elevated serum triglycerides and reduced serum high density lipoprotein cholesterol was high in the "Rice & Kimchi" dietary pattern compared to the other dietary pattern groups. CONCLUSION: Because adolescents' dietary patterns are changing continuously and have long-term effects, further studies on the dietary patterns of adolescents and their health effects into adulthood are necessary.

Clinical Analysis of Acinic Cell Carcinoma in Parotid Gland

OBJECTIVES: Acinic cell carcinoma (AciCC) is a rarely encountered malignancy in parotid gland. Because AciCC is rare and was recently recognized as the entity of malignancy, AciCC has been difficult to study. We aimed to analyze the diagnosis and treatment experience for this malignancy in our hospital. METHODS: We retrospectively reviewed medical records of the 20 patients with AciCC of parotid gland diagnosed from 1990 to 2009. The preoperative computed tomography scan, preoperative fine needle aspiration cytology (FNAC) and intraoperative frozen section results were compared with the final diagnosis. The survival and recurrence were analyzed with the cancer stages and treatment modalities. RESULTS: There were 10 males and 10 females, with a mean age of 44.4 years, ranging 8-77 years. The AJCC tumor stage distributions of the patients were 70%, 15%, and 15% for stages I, II, and IV, respectively. The sensitivity of FNAC and intraoperative frozen section was 26.7% and 50.0% respectively. The 10-year survival rate was 90.9% with a mean follow-up of 111 months, ranging 17-251 months. The 10-year disease free survival rate was 74.2% and the mean duration of recurrence from initial surgery was 92.3 months. CONCLUSION: AciCC of the parotid gland is a rare malignancy that has features of less aggressive behavior, and good prognosis. Intraoperative frozen section examination may be helpful in the diagnosis of AciCC of the parotid gland because of the low sensitivity of preoperative computed tomography scan and FNAC. Surgery with adjuvant postoperative radiotherapy is satisfactory for disease control.

Vascular Malformation of Flexor Hallucis Longus Muscle Associated with a Flexion Deformities of Toes: A Case Report / 대한골관절종양학회지

Vascular malformations may typically present with palpable mass that can be either asymptomatic or can present with symptoms including swelling and pain. On rare occasions, vascular malformation of muscle may produce joint deformities caused by contracture of the involved muscle. When vascular malformation involves the flexor muscle of the leg, ankle equinus deformity may occur. However, there are no reports of toe deformities secondary to intermuscular or intramuscular vascular malformations of flexor muscles of toe. Thus, we report a case of vascular malformation of flexor hallucis longus muscle with flexion contracture of toes in a 40-years-old woman who was treated with surgical excision.

The Effect of Decreases in Left Ventricle Volume and Area During Ventricular Fibrillation on Resuscitation Outcomes

PURPOSE: Dynamic changes in the dimensions of the left ventricle (LV) during cardiac arrest might influence the efficacy of CPR. However, the relationship between change in LV dimensions during cardiac arrest and CPR hemodynamics and outcomes have not yet been addressed. In the present study, we investigated changes in left ventricular volume and area during prolonged, untreated ventricular fibrillation (VF); we related those change to coronary perfusion pressure (CPP) during CPR and resuscitation outcomes. METHODS: In 12 domestic male pigs weighing 40+/-3 kg, VF was electrically induced and left untreated for 15 min. CPR was performed for 5 min prior to defibrillation. CPR was continued until the return of spontaneous circulation (ROSC) or for a maximum of 15 minutes. Mean aortic pressure and right atrial pressures were measured and CPP was calculated. LV dimensions were continuously assessed by echocardiographic measurement during the 15 minutes of interval VF. RESULTS: Six animals were successfully resuscitated. During the 15 minute interval of VF, LV area and volume were reduced in all animals. In animals that were not resuscitated, LV dimensions were significantly lower than those in resuscitated animals (p<0.01). These differences were observed after 10 minutes of VF. The animals with greater reduction in LV dimension during VF achieved significantly lower CPP during CPR in contrast to animals with larger LVs during VF. CONCLUSION: Greater decreases in LV volume and area during cardiac arrest are associated with low CPP during CPR and poor resuscitation outcomes. LV dimensions prior to starting CPR might therefore modulate the effectiveness of resuscitation interventions.

The Effects of 'Hands Only(TM)' Cardiopulmonary Resuscitation (CPR) in CPR Education in Elementary School

PURPOSE: The success of cardiopulmonary resuscitation (CPR) depends on how soon after a heart attack the intervention is done and on how the quality of the CPR is. Although in Korea there are several CPR education courses, CPR done by bystanders to an attack remains very low. This might be related to different causes such as the complexity of the CPR sequence and the difficulty of learning CPR, specifically ventilation maneuvers. The American Heart Association (AHA) has recently recommended 'Hands Only(TM) CPR', without ventilation, for bystander rescuers. In the present study, we investigated the educational effects of 'Hands Only(TM) CPR' in elementary school students. We further analyzed the effects of this variable on CPR skill learning and retention for a 3 months period. METHODS: We selected two groups of 5th grade elementary school students to perform this study. One group received CPR education with ventilation (CPR with ventilation group); the other received 'Hands Only(TM) CPR' education ('Hands Only(TM) CPR' group). The Laerdal PC Skill Reporting system was used for both education sessions and for evaluation immediately after the sessions. Skill performance data, together with ventilation data and compression data were recorded for further comparisons. RESULTS: There were no differences between the two groups regarding chest compression (average rate, average duty cycle, registered with no error, average depth, etc.). The average chest compression count per minute was 118+/-12/min in the 'Hands Only(TM) CPR' group and 85+/-13/min in the CPR with ventilation group (p=0.001). Registered adequate compression depth was 23+/-29% in the 'Hands Only(TM) CPR' group and 23+/-31% in the CPR with ventilation group (p=0.962). The total hands off time was 18+/-7 seconds in the 'Hands Only(TM) CPR' group and 40+/-11 seconds in the CPR with ventilation group. After 3 months there were still no differences in chest compression between the two groups. The average count per minute at 3 months was 109+/-15/min in the 'Hands Only(TM) CPR' group and 83+/-17/min in the CPR with ventilation group (p=0.001). Registered adequate compression depth was 26+/-31% in the 'Hands Only(TM) CPR' group and 31+/-35% in the CPR with ventilation group (p=0.334). The total hands off time was 12+/-5 seconds in the 'Hands Only(TM) CPR' group and 31+/-12 seconds in the CPR with ventilation group (p=0.001). CONCLUSION: The 'Hands Only(TM) CPR' program in elementary school children increased the chest compression rate. However, there was no between groups difference in adequate compression depth. We were unable to demonstrate that the 'Hands Only(TM) CPR' education program in elementary school children led to a better effect.

Photodynamic therapy using topically applied 5-aminolevulinic acid for treatment of cervical cancer / 대한산부인과학회지

OBJECTIVE: The purpose of this study was to investigate the treatment effects of a topical application of 5-aminolevulinic acid (5-ALA) for photodynamic therapy (PDT) to treat cervical cancer. METHODS: We first investigated the effects of 5-ALA cream according to application time. And to find the effective 5-ALA concentration and the distribution times in vivo, 20% 5-ALA cream was topically applied to the tumor of the nude mouse. We then observed the distribution of 5-ALA via fluorescence measurement with using a 532 nm diode laser. 25 nude mice were divided into Control, ALA, Laser, and PDT group. To evaluate the PDT effect at cancer lesion, we applied 20% 5-ALA cream to the tumor by the same method, and the PDT was done by using a 632 nm diode laser at the time of the peak level of fluorescence. We checked the changes of the volume of cancer for 30 days, and then biopsy was done. RESULTS: The effective post-irradiation time after topical ALA application was 9 hours. In the PDT group, 40% (4/10) of the mice showed decreased tumor size. CONCLUSION: The maximum PpIX fluorescence at 9 hours after local applicationof 5-ALA cream was checked. And PDT group did not show any statistical difference than control group in the growth of tumor size than control group. However responding cases (4/10) of PDT group showed the meaningful decrease of tumor size than control group (P<0.05).

Two Cases of ANCA-associated Pauci-immune Glomerulonephritis with Rheumatoid Arthritis / 대한류마티스학회지

Renal involvement is one of the extra-articular manifestations found in patients with rheumatoid arthritis (RA). Membranous glomerulonephopathy, membranoproliferative glomeruonophritis, secondary amyloidosis, and focal segmental glomerulosclerosis are reported as pathologic diagnoses of renal involvement. However, reports of renal involvement in patients with RA and antineutrophil cytoplasmic autoantibody (ANCA)-associated pauci-immune glomerulonephritis are rare. Recently, we experienced two patients with RA who developed azotemia and were finally diagnosed with ANCA-associated pauci-immune glomerulonephritis. Because of the rarity of these cases, we report two cases in patients with RA with a literature review.

Viability of Chondrocytes in the Crushed Septal Cartilage Depending on Degree of Crushing and Their Mechanism of Cell Death / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: To analyze the viability of chondrocytes according to different degrees of crushing and to investigate the mechanism of cell death in the crushed cartilage. SUBJECTS AND METHOD: Septal cartilages were obtained from 22 patients and cartilage pieces were allocated to four groups; normal, mildly crushed, moderately crushed and severely crushed. The cartilage specimens were stained with hematoxylin-eosin and examined under light microscope. The viability of the chondrocytes and the mechanism of cell death were assessed using confocal laser scanning microscopy. RESULTS: As crushing intensity increased, chondrocyte viability significantly decreased. The mechanism of cell death was mainly due to necrosis rather than apoptosis. CONCLUSION: The viability of chondrocytes in the crushed cartilage depends on the degree of crushing. The mechanism of cell death after crushing is mainly necrosis. Therefore, for the clinical use of the crushed cartilage, slight overcorrection and standardization of the degree of crushing are recommended.

Preventive and Therapeutic Effects of Low Level Laser Irradiation on Gentamicin-Induced Vestibulotoxicity in Rat Utricles / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The purpose of this study was to investigate the effects of low level laser for the prevention and treatment of aminoglycoside-induced vestibular ototoxicity. MATERIALS AND METHOD: An organotypic culture of 2 to 4 days old rat utricular maculae was established. Rats were divided into 6 groups according to the treadtment of the utricles: G (gentamicintreated), L (laser-irradiated), LG (laser-irradiated and gentamicin-treated), GL (gentamicin-treated and laser-irradiated), LGL (gentamicin-treated during laser-irradiated) and C (control). After organotypic culture, the utricles of 6 groups were examined by confocal laser scanning electron microscope and scanning electron microscope. The results of each group were compared with each other by statistical methods. RESULTS: The number of vestibular hair cells of the group G was smaller compared to that of the group C. The group L had no difference compared with the group C. The groups LG and GL showed more vestibular hair cells compared with the group G. The group LG showed more vestibular hair cells than the group GL. The group LGL showed most vestibular hair cells compared to that of the groups G, LG, and GL. CONCLUSION: The most effective treatment of aminoglycosideinduced vestibular otoxicity is the irradiation of low level laser before and after the insult of the aminoglycoside. Further clinical studies using low level laser were needed to prevent aminoglycoside-induced ototoxicity and to promote the regeneration of vestibular hair cells.

Antioxidant and Anti-Apoptotic Effect of Melatonin on the Vestibular Hair Cells of Rat Utricles

OBJECTIVES: Aminoglycosides are commonly used antibiotic agents, and they are known to generate free oxygen radicals within the inner ear and to cause vestibulo-cochlear toxicity and permanent damage to the sensory hair cells and neurons. Melatonin, a pineal secretory product, has the properties of being a powerful direct and indirect antioxidant. The aim of the present study was to prove the antioxidant effect of melatonin against gentamicin-induced ototoxicty. METHODS: The utricular maculae of Sprague-Dawley rats were prepared from postnatal day 2-4, and these maculae were were divided into 6 groups as follows: 1) control, 2) melatonin only, 3) gentamicin only, and 4), 5), and 6) gentamicin plus melatonin (10, 50, and 100 micrometer, respectively). To count the number of hair cells, 5 utricles from each group were stained with phalloidin-FITC on the 1st, 4th, and 7th days after drug administration. Reactive oxygen species (ROS) was assessed by using the fluorescent probe hydrofluorescent diacetate acetyl ester. The caspase-3 activity was also examined with using the fluorescent caspase-3 substrate and performing Western blotting. RESULTS: The result of this study showed that gentamicin induced the loss of utricular hair cells, and this loss of hair cells was significantly attenuated by co-administration of melatonin. Melatonin reduced ROS production and caspase-3 activation in the gentamicin treated utricular hair cells. CONCLUSION: Our findings conclusively reveal that melatonin has protective effects against gentamicin-induced hair cell loss in the utricles of rat by inhibiting both ROS production and caspase-3 activity.

The correlation between the effects of propofol on the auditory brainstem response and the postsynaptic currents of the auditory circuit in brainstem slices in the rat / 대한마취과학회지

BACKGROUND: Although there have been reports showing the changes of the auditory brainstem response (ABR) waves by propofol, no detailed studies have been done at the level of brainstem auditory circuit. So, we studied the effects of propofol on the postsynaptic currents of the medial nucleus of the trapezoid body (MNTB)-lateral superior olive (LSO) synapses by using the whole cell voltage clamp technique and we compared this data with that obtained by the ABR. METHODS: 5 rats at postnatal (P) 15 days were used for the study of the ABR. After inducing deep anesthesia using xylazine 6 mg/kg and ketamine 25 mg/kg, the ABRs were recorded before and after intraperitoneal propofol injection (10 mg/kg) and the effects of propofol on the latencies of the I, III, and V waves and the I-III and III-V interwave intervals were evaluated. Rats that were aged under P11 were used in the voltage clamp experiments. After making brainstem slices, the postsynaptic currents (PSCs) elicited by MNTB stimulation were recorded at the LSO, and the changes of the PSCs by the bath application of propofol (100 microM) were monitored. RESULTS: We found small, but statistically significant increases in the latencies of ABR waves III and V and the interwave intervals of I-III and III-V by propofol. However, no significant changes were observed in the glycinergic or glutamatergic PSCs of the MNTB-LSO synpases by the application of propofol (100 microM). CONCLUSIONS: Glycinergic or glutamatergic transmission of the MNTB-LSO synapses might not contribute to the propofol-induced changes of the ABR.

Change of Nitric Oxide Synthase Expression and Dynamic Ciliary Activity Responding to Nitric Oxide in Sinusitis Mucosa / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: There are conflicting results about ciliary activity in chronic rhinosinusitis (CRS). Dynamic movements reacting to various stimuli in CRS mucosa have been rarely studied. This study was designed to investigate the dynamic ciliary activity in response to nitric oxide stimulation in sinusitis. We aimed to identify the difference in the expression of nitric oxide synthase (NOS) in normal and CRS mucosa. SUBJECTS AND METHOD: Nasal mucosal samples were obtained from 25 sinusitis and 15 normal subjects. We measured ciliary beat frequency (CBF) in the basal and activated status. Immunohistochemial staining was used to evaluate the expression of NOS in the sinusitis. RESULTS: The CRS mucosa showed marked differences in the CBF changes stimulated by NO compared to the normal mucosa; both the maximal increase and duration of increase of CBF by NO were significantly reduced in CRS mucosa. The results of immunohistochemical stain showed that eNOS expression was evident in the normal nasal mucosa and iNOS expression was markedly increased in CRS mucosa. CONCLUSION: Dynamic ciliary activity responding to NO was markedly attenuated in the CRS mucosa. The L-NAME markedly attenuated the duration of increase and maximal increase of CBF by ATP both in the normal and CRS mucosa. eNOS expression was relatively evident in the normal mucosa, whereas iNOS expression was relatively increased in the CRS mucosa, implicating different actions of NO on CBF.