이황화탄소 중독과 심박동수 변이와의 관련성

전형준,임상혁,백도명 大韓産業醫學會 2004 대한직업환경의학회지 Vol.16 No.1

목적: 1980년대 말에 레이온 섬유를 생산하는 업체에서 대규모 이황화탄소 중독 사례가 발생하였으며 1998년까지 사망자 38명을 포함하여 830명의 근로자들이 이황화탄소 중독으로 진단되었다. 이황화탄소 중독으로 진단 받았던 환자들과 정상인들의 심박동수 변이를 측정하여 이황화탄소 노출이 중단된 상태에서의 건강영향에 대해 조사하였다. 아울러 환자군을 대상으로 이황화탄소 노출량과 심박동수 변이와의 사이에 양-반응 관계가 있는 지를 조사하였다. 방법: 이황화탄소 중독으로 진단된 71명의 남성 퇴직 근로자들을 환자군으로, 이황화탄소를 포함한 유기용제에 직업적으로 노출된 적이 없고 심혈관계질환이 없는 환자군과 같은 연령대의 남성 127명을 대조군으로 선정하였다. 두 군에서 자기 기입식 설문지를 이용하여 연령, 흡연, 음주, 규칙적인 운동, 과거의 직업력 및 질병력 등에 대한 정보를 수집하였다. 건강검진을 통해 신장, 체중, 혈압을 측정하고 심전도 검사, 흉부 방사선 촬영 등을 실시하였다. 심박동수 변이의 지표로서 시간 영역(maximum, average, minimum RR interval)과 주파수 영역(low frequency - LF, high frequency - HF, total power spectrum - TPS, LF/HF ratio)을 측정하였다. 환자군에서 과거의 이황화탄소 노출에 대한 지표들(근무기간, 근무부서별 노출량, 누적노출지수, 퇴사기간)을 조사하여 심박동수 변이와 양-반을 관계가 있는 지를 평가하였다. 결과: 단변량 분석에서 두 군의 시간 영역 측정치에는 유의한 차이가 없었다. 이에 비해 고주파 영역을 제외한 주파수 영역 측정치들은 환자군들이 대조군에 비해 유의하게 낮았다. 다중선형분석에서 이황화탄소 중독의 과거력은 모든 주파수 영역 변수들과 음의 관계를 나타냈으며, 특히 저주파 영역(p<0.05)과 저주파/고주파 비(p<0.05)에 유의한 영향을 나타냈다. 환자군에서 이황화탄소 노출 지표들과 심박동수 변이와의 양-반응 관계를 조사하였으나 유의한 관계는 나타나지 않았다. 결론: 환자군에서 이황화탄소와 심박동수 변이와의 사이에 양-반응관계를 확인할 수는 없었으나 환자군과 정상인을 비교했을 때 저주파 영역과 저주파/고주파 비 등에서 심박동수 변이의 감소가 있었다. 이황화탄소의 노출이 중단된 상태에서도 심혈관계 건강영향이 있을 가능성에 대한 연구가 더 필요하다. Objectives: Mass poisoning by carbon disulfide (CS_(2)) occurred in a viscose rayon factory in Korea. Up until 1998, 830 employees, including 38 who had died, were diagnosed with CS_(2) poisoning. Among the CS_(2) poisoned subjects, heart rate variability (HRV) was evaluated to investigate whether the toxic effect of CS_(2) persists after the exposure has ceased. The dose-response relationship between carbon disulfide exposure and HRV was also evaluated. Methods: The case group was comprised of 71 retired male workers diagnosed as being CS_(2) poisoned. The control group was comprised of 127 males of same age-range who had no history of CS_(2) exposure and cardiovascular diseases. Information on individual age, height, weight, weight, cigarette smoking, alcohol drinking, regular exercise, medical and occupational history, chest x-ray, and ECG recording of the two groups were collected through a self-administered questionnaire and with a medical examination, Time (maximum, average, minimum RR interval) and frequency domain measures (low frequency - LF, high frequency - HF, total power spectrum TPS, and LF/HF ratio) of the two groups were analyzed. CS_(2) exposure indices of the case group (duration of employment, exposure level per work department, cumulative exposure index and duration of retirement) were investigated. Results: Using a univariate analysis, the frequency domain measures for the case group were significantly lower than those in the control group, except for HF. In the multivariate analysis, previous history of CS_(2) poisoning was inversely related to all frequency domain parameters and it significantly affected the LF(p<0.05). There was no significant dose-response relationship between CS_(2) exposure indices and HRV parameters in the case group. Conclusion: This study suggests that further studies are necessary to evaluate the residual effects of CS_(2) poisoning even after the CS_(2) exposure has ceased.

이황화탄소 중독자들의 노출중단 이후의 심박동수 변이

이상윤,조성일,백도명,변창범,김미정,박경근,임상혁,양길승,황창국,전형준 大韓産業醫學會 2006 대한직업환경의학회지 Vol.18 No.2

목적: 2000년도에 이황화탄소 중독증 환자들과 대조군의 심박동수 변이를 비교하여 이황화탄소 중독증 환자들의 심박동수 변이가 대조군에 비해 유의하게 낮다는 연구보고가 있었다. 당시의 연구가 이황화탄소 노출이 중단된 상태에서 이황화탄소 중독자들의 건강 문제를 연구했다는 점에 의의가 있으나 연구 결과를 해석하는데 있어 제한점들이 있었다. 이 연구는 2000년도에 수행하였던 연구의 제한점을 극복하고 이황화탄소 노출이 중단된 이후의 이황화탄소 중독자들의 심혈관계 상태를 심박동수 변이를 이용하여 평가해보고자 하였다. 방법: 이황화탄소 중독증으로 진단받은 환자 122명과 환자군의 연령대와 성별 빈도에 따라 무작위 추출한 112명을 대조군으로 선정하였다. 자기 기입식 설문지와 건강검진을 통해 연령, 성별, 신장, 체중, 흡연, 음주, 규칙적 운동, 질병력, 직업력, 흉부 방사선 촬영, 심전도 측정을 실시하였다. 연구 대상자들은 의자에 앉힌 상태에서 5분 동안 심박동수 변이를 측정하였다. 이 연구에서 측정한 심박동수 변이 지표들은 정상 RR간격의 표준편차(standard deviation of all norma-to-normal intervals, SDNN), 인접한 RR간격들의 차이를 제곱의 합의 평균의 제곱근(square root of the mean of the sum of squares of differences between adjacent normal-to-normal intervals, RMSSD). 저주파영역(low frequency power, LF: 0.04~0.15Hz), 고주파 영역 (high frequency power, HF:0.15~0.4Hz), 전체 주파수 강도(total power, TP), 저주파/고주파 비 (LF/HF ratio)이다. 결과: 단변량 분석에서 이황화탄소 중독자들의 모든 심박동수 변이 지표들이 대조군에 비하여 낮았다. 다중선형회귀분석에서 이황화탄소 중독은 RMSSD를 유의하게 감소시키는 것으로 나타났다.(P<0.05). 결론: 이 연구는 이황화탄소 노출이 중단된 상태에서도 이황화탄소 중독자들에게 심혈관계와 관련된 건강문제가 있을 수 있음을 시사한다. Objectives: A previous study conducted in 2000 measuring the heart rate variability (HRV) of carbon disulfide (CS_(2))-poisoned subjected suggested that their HRV was reduced after exposure cessation. However, the study was limited by the following procedural limitations: (1) only 71 CS_(2)-poisoned subjects participated, (2) no females participated, and (3) the CS_(2)-poisoned subjects were older than the controls. This study was therefore conducted to overcome these limitations of the earlier study. Methods: The study subjects comprised 122 retired workers with CS_(2) poisoning and the same number of age- and sex-matched controls. Information on individual age, sex, height, wight, smoking history, alcohol drinking, regular exercise, medical and occupational history, chest x-ray, and ECG recording of the two groups was collected though a self-administered questionnaire and a medical examination. Standard Deviation of NN intervals (SDNN), Root-Mean-Square of Successive Differences (RMSSD), Total Power (TP), Low Frequency (LF), High Frequency (HF), and LF/HF ratio were measured as HRV indices for 5 minutes in the sitting position. Results: Univariate analysis revealed that all HRV indices of CS_(2)-poisoned subjected were lower than those of the controls. Multiple linear regression analysis showed that CS_(2) poisoning had negative association with all HRV indices and that its association with RMSSD was statistically significant(P<0.05). Conclusions: This study suggests that CS_(2)-poisoned subjects continue to have reduced HRV, even though the exposure has ceased.

대한간학회 학술연구기금 지원과제 결과 보고 : 클레부딘 내성 만성 B형간염의 치료에 대한 다기관 후향 및 전향 연구

( Hyung Joon Yim ),( Eun Young Cho ),( Eileen L. Yoon ),( Yeon Seok Seo ),( Ji Hoon Kim ),( Hong Soo Kim ),( Se Hwan Lee ),( Sang Hoon Ahn ),( Sook Hyang Jeong ),( Jin Wook Kim ),( Jeong Il Lee ),( Ji 대한간학회 2011 Clinical and Molecular Hepatology(대한간학회지) Vol.17 No.5(S)

A Randomized Controlled Study to Compare Efficacy of Terlipressin 6 mg/day and Terlipressin 4 mg/day in Patients with Hepatorenal Syndrome

( Hyung Joon Yim ),( Sang Jun Suh ),( Yeon Seok Seo ),( Soo Young Park ),( Young Oh Kweon ),( Young Kul Jung ),( Yun Soo Kim ),( Moon Young Kim ),( Sae Hwan Lee ),( Heon Ju Lee ),( Joo Hyun Sohn ),( J 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Hepatorenal syndrome (HRS) exhibits grave prognosis. To improve the outcome of HRS, we compared the efficacies of higher dose (6 mg) vs. standard dose (4 mg) of terlipressin. Methods: The inclusion criteria were cirrhotic patients with type-I HRS. The cut-off of creatinine (Cr) for inclusion was initially >2.5 mg/dL, but was lowered to >1.5 mg/dL during the study period upon update of the Diagnostic Criteria. After randomization, patients received the 1 mg of terlipressin intravenously every 4 hours (test group) or every 6 hours (control group) together with albumin infusion for 15 days. If the Cr was not improved by >30% after 72 hours of initiation, the dose was increased to 12 mg/day in the test group. The primary end point was decrease of serum Cr to a value of 1.5 mg/dL or serum Cr level of less than 50% compared with the baseline value. As a post-hoc exploratory analysis, we compared the clinical outcome of the patients who had baseline Cr <2.5 mg/dL vs. ≥ 2.5 mg/dL. Results: A total of 60 patients were enrolled. Sixteen of 29 patients (55.2%) achieved the primary end point in the test group, while 15 of 31 patients (48.4%) achieved it in the control group (P = 0.735). The survival rates at day 15 were 58.6% (17/29) and 64.5% (20/31), respectively (P = 0.639). In the post-hoc analysis, achievement rates of the primary end point were not different in patients with baseline Cr<2.5 mg/dL vs ≥2.5 mg/dL, either (66.7% vs. 46.7%, respectively, P = 0.180). However, rate of Cr normalization to <1.5 mg/dL (66.7% vs. 26.7%, respectively, P = 0.005) and the survival rate at day 15 (92.9% vs. 48.8%, respectively, P = 0.004) were significantly higher in patients with Cr<2.5 mg/dL than in patients with Cr≥ 2.5 mg/dL at baseline. Conclusions: Higher dose of terlipressin did not improve the outcome of HRS. However, early initiation of terlipressin may improve the response rate and the survival in patients with HRS.

Corrigendum to: Is Neoadjuvant Therapy Needed in Patients with Resectable Pancreatic Cancer?

Yim Hyung Joon 거트앤리버 소화기연관학회협의회 2023 Gut and Liver Vol.17 No.2

Comparison of Daily Norfloxacin versus Weekly Ciprofloxacin for the Prevention of Spontaneous Bacterial Peritonitis in Cirrhotic Patients: A Randomized Controlled Trial

( Hyung Joon Yim ),( Sang Jun Suh ),( Young Kul Jung ),( Sun Young Yim ),( Yeon Seok Seo ),( Soo Young Park ),( Jae Young Jang ),( Young Seok Kim ),( Hong Soo Kim ),( Byung Ik Kim ),( Kwang-hyub Han ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: For the prevention of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites, norfloxacin 400mg per day is a standard regimen. However, ciprofloxacin 750 mg per week is also known to be effective. In addition, ciprofloxacin once weekly administration is more convenient and less costly. This study aims to prove that ciprofloxacin once weekly administration is as effective as norfloxacin once daily administration for the prevention of SBP. Methods: Liver cirrhosis patients with ascites between 20-75 years old were screened, and enrolled in this randomized controlled trial if 1) ascitic polymorphonucleated cell count < 250/mm3 2) ascitic protein is equal or less than 1.5 g/dL or 3) the presence of history of SBP. Patients were randomly assigned into norfloxacin daily or ciprofloxacin weekly group, and followed-up for 12 months. Primary end point was the prevention rate of SBP, and the secondary end points were 1 year mortality, incidence of infectious events, hepatorenal syndrome, and hepatic encephalopathy. Results: 124 patients were enrolled and allocated into each group by 1:1 ratio (62:62). Male patients were 90% and the mean age was 55.2 ± 10.1. The mean Model for End stage Liver Disease (MELD) score was 14.6 ± 4.8. There was no difference in baseline characteristics between the groups. SBP developed in 2 patient of ciprofloxacin group, and in 3 patients of norfloxacin group (3.2% vs. 4.8%, P = 0.643). Cumulative transplant free survival rate were comparable between the groups (80.6% vs. 82.3%, P = 0.863). Incidence of infectious complication, hepatorenal syndrome, hepatic encephalopathy, and variceal bleeding rates were not significantly different (all P = ns). The only factor related to survival was underlying liver function MELD, P = 0.001). Conclusions: Once weekly ciprofloxacin was as effective as daily norfloxacin for the prevention of SBP in cirrhotic patients with ascites. NCT01542801]

Free Paper Session : Hepatitis B ; Adding adefovir compared with switching to entecavir in patients with Lamivudine-resistant chronic hepatitis B (ACE study) - a multicenter prospective randomized study: final results (초)

( Hyung Joon Yim ),( Ei Leen Yoon ),( Yeon Seok Seo ),( Chang Wook Kim ),( Chang Don Lee ),( Sang Hoon Park ),( Myung Seok Lee ),( Choong Kee Park ),( Hee Bok Chae ),( Moon Young Kim ),( Soon Koo Baik 대한간학회 2011 Clinical and Molecular Hepatology(대한간학회지) Vol.17 No.3(S)

Comments on Comparison of Sorafenib versus Hepatic Arterial Infusion Chemotherapy-Based Treatment for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: Reply

Yim Hyung Joon,Ahn Young Eun,Kim Tae Hyung,Jung Young Kul 거트앤리버 소화기연관학회협의회 2023 Gut and Liver Vol.17 No.2

Efficacy of Sorafenib Monotherapy versus Transarterial Chemoembolization (TACE)-Sorafenib Sequential Therapy in Patients with Extrahepatic Metastasis - An Interim Analysis of Randomized Controlled Trial

( Hyung Joon Yim ),( Sang Jun Suh ),( Young Kul Jung ),( Sung-bum Cho ),( Woo Jin Chung ),( Young Seok Kim ),( Si-hyun Bae ),( Jun Young Park ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Sorafenib is the standard therapy for hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM). However, transarterial chemothembolization (TACE) which is a standard therapy for intermediate stage may be beneficial for controlling intrahepatic tumour, thereby providing chance of improving survival in HCC patients with EHM. We aimed to compare the efficacy between the sorafenib monotherapy and TACE-sorafenib sequential therapy in HCC patients with EHM. Methods: This study is a prospective randomized controlled study conducted at 6 tertiary hospitals in South Korea. HCC patients with EHM were enrolled and randomized into sorafenib monotherapy or TACE-sorafenib sequential therapy group. Patients with main portal vein invasion, Child-Pugh class B or C, and history of TACE or previous systemic therapy were excluded. The sorafenib monotherapy group received sorafenib immediately after randomization while the TACE-sorafenib group received 2~4 times of TACE before starting sorafenib. Response evaluation was performed every 2 months, and overall survival (OS), time to progression (TTP), and progression free survival (PFS) were compared. We initially planned 130 patients for the present study, and the results of interim analysis are presented. Results: A total of 65 patients were enrolled currently: 33 patients into the monotherapy and 32 into the sequential therapy group. Baseline characteristics of the patients such as gender, age, aetiology of liver disease, Child-Pugh score, HCC stage, and tumour burden were not significantly different between two groups. Median OS were 6.4 (0.4-30.6) months and median TTP were 3.5 (0.9-25.7) months in all patients. The probability of survival rates were plotted by Kaplan-Meier curve and compared by log-rank test. Median OS were not different in both groups: monotherapy 4.3 (0.4-30.6) months and sequential therapy 7.4 (1.8-25.7) months (P=0.364). However, median TTP were longer in sequential therapy group: monotherapy 2.6 (0.9-9.3) months and sequential therapy 4.6 (1.0-25.7) months (P=0.003), and the median PFS were also better in the sequential therapy group: monotherapy 2.6 (0.4-9.3) months and sequential therapy 4.6 (1.0-25.7) months (P=0.015). The disease control rate were better in sequential therapy group: monotherapy 40.7% and sequential therapy 71.0% (P=0.020). Conclusions: The TACE-sorafenib sequential therapy would be a better strategy than sorafenib monotherapy for the treatment of HCC patients with EHM, especially, in controlling tumour progression.

Comparison of Efficacy of Cefotaxime, Ceftriaxone, and Ciprofloxacin for the Treatment of Spontaneous Bacterial Peritonitis: A Randomized Controlled Trial

( Hyung Joon Yim ),( Sang Jun Suh ),( Young Kul Jung ),( Moon Young Kim ),( Soon Koo Baik ),( Hong Soo Kim ),( Young Seok Kim ),( Soo Young Park ),( Byung Ik Kim ),( Jun Yong Park ),( Heo Jung ),( Kwa 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: For the treatment of spontaneous bacterial peritonitis (SBP), intravenous antibiotics such as cefotaxime, ceftriaxone, or ciprofloxacin has been used as the first-line agents for a period of time. However, considering the increasing rate of antibiotic resistance, it is unclear which of these drugs is still effective. The aim of study is to compare the efficacy of the three current antibiotics for the treatment of SBP in patients with liver cirrhosis and ascites. Methods: This is a multicenter prospective randomized controlled trial. The primary hypothesis is that the efficacy of all the antibiotics would not be significantly different. This is a non-inferiority trial, and 87 patients for each group were needed to demonstrate it. Inclusion criteria were 16-70 years old liver cirrhosis patients with ascites, of which polymorphonuclear (PMN) cell count >250/mm³. Patients with any evidence of secondary peritonitis were excluded. We administered antibiotics after randomization, and performed follow-up paracentesis at 48 hours (day 2) and 120 hours (day 5) of treatment for the assessment of resolution rates: decrease of PMN cell count in the ascetic fluid less than <250/mm³ at day 5 was the primary efficacy endpoint. Results: This study was conducted at 9 tertiary hospitals of 7 universities. A total of 261 liver cirrhosis patients who developed SBP were enrolled. The resolution rates of SBP at day 5 were 69.1%, 76.2%, and 76.1% in cefotaxime, ceftriaxone, and ciprofloxacin group, respectively. The efficacy was not different between the groups (P = 0.565). The early resolution rate of SBP at 48 hours were 54.5%, 53.1% and 51.9% (P = 0.946). The 1 month mortality after SBP was similar between the groups (P = 0.628). MELD score (OR 1.074, CI 1.009-1.144, P = 0.026) and the resolution at day 5 (OR 0.251, CI 0.094-0.670, P = 0.006) were significant factors for survival. Conclusions: The efficacy of primary antibiotics such as cefotaxime, ceftriaxone, and ciprofloxacin were not significantly different. It is considered that these antibiotics are still efficacious as an initial treatment. MELD score and the resolution of SBP at day 5 were most important factors for short term survival.