• Journal of Nutrition and Health
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• 제42권8호
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• pp.673-681
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• 2009

Diabetes mellitus is a multifactorial disease. Particularly, diabetic nephropathy is a serious complication for diabetic patients, yet the precise mechanisms that underline the initial stage of diabetic renal inflammation remain unknown. However, oxidative stress induced by hyperglycemia in diabetes is implicated in diabetic renal disease. We hypothesized that dietary supplementation of antioxidants either VCE (0.5% VC + 0.5% VE) or Comb (0.5% VC + 0.5% VE + 2.5% N-acetylcysteine) improves acute diabetic renal inflammation through modulation of blood glucose levels and antioxidant and anti-inflammatory responses. Experimental animals (5.5 weeks old female ICR) used were treated with alloxan (180 mg/kg) once. When fasting blood glucose levels were higher than 250 mg/dL, mice were divided into 3 groups fed different levels of antioxidant supplementation, DM (diabetic mice fed AIN 93G purified rodent diet); VCE (diabetic mice fed 0.5% vitamin C and 0.5% vitamin E supplemented diet); Comb (diabetic mice fed 0.5% vitamin C, 0.5% vitamin E and 2.5% N-acetylcysteine supplemented diet), for 10 days and then sacrificed. Body weights were measured once a week and blood glucose levels were monitored twice a week. Lipid peroxidation products, thiobarbituric acid reacting substances were measured in kidney. NF-${\kappa}B$ activation was indirectly demonstrated by pI${\kappa}B$-${\alpna}$ and expressions of selective inflammatory and oxidative stress markers including antioxidant enzymes were also determined. Dietary antioxidant supplementation improved levels of blood glucose as well as kidney lipid peroxi-dation. Dietary antioxidant supplementation improved NF-${\kappa}B$ activation and protein expression of HO-1, but not mRNA expression levels in diabetic mice fed Comb diet. In contrast, the mRNA and protein expression of CuZnSOD was decreased in diabetic mice fed Comb diet. However, antioxidant supplementation did not improve mRNA and protein expressions of IL-$1{\beta}$ and MnSOD in diabetic mice. These findings demonstrate that acute diabetic renal inflammation was associated with altered inflammatory and antioxidant responses and suggest that antioxidant cocktail supplementation may have beneficial effects on early stage of diabetic nephropathy through modulation of blood glucose levels and antioxidant enzyme expressions.

• 한국의료질향상학회지
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• 제9권2호
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• pp.116-133
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• 2002

Background : It is very common in Korea to take care of non-acute patients in an acute setting, due to the lack of long-term facilities. Long term hospitalization increase medical expenses and decreases the bed utilization, which can affect the urgent and emergent admissions, and eventually jeopardize the hospital financially. In this study, strategies for effective transfers to the lower levels of care, and to decrease the length of stay were presented by surveying and analyzing the patient's knowledge of the transfer needs, and the willingness to transfer those whose hospital length of stay was more than 30days. Method : The survey is subject to a group of 251 patients who have been hospitalized over 30 days in a general hospital in Seoul. Excluding those that were in the Intensive Care Unit and psychiatric ward, 214 in-patients were used as participants. They were surveyed from April 9, 2002 to April 17, 2002. One hundred and thirty seven out of 214 were responded which made the response rate 64%. Data were analyzed by SAS and SPSS. Result : Multi-variable Logistic Regression Analysis showed a significant effect in medical expenses, knowledge of referral system and the information of the receiving hospital. The financial burden in medical expenses made the patient 10.7 times more willing to be transferred, knowledge of the referral system made them 5 times more willing to be transferred, and the information of receiving hospital makes 6.5 times more willing to be transferred. Reasons for willing to be transferred to a lower level of care were the phase of physical therapy, the distance from home, the attending physician's advice and being unable to be treated as an out patient. Reasons for refusing to be transferred were the following. The attending physician's competency, not being ready to be discharged, not trusting the receiving hospital's competency due to the lack of information, or never hearing about the referring system by the attending physician. Conclusion : Based on this, strategies for the effective transfer to the lower levels of care were suggested. It is desirable for the attending physician to be actively involved by making an effort to explain the transfer need, and referring to the Healthcare Coordinating Center, which can help the patient make the right decision. Nationwide networking for the referral system is the another key factor that may need to be suggested as an alternative to decrease the medical expenses. Collaborating with the Home Health Agency for the early discharge planning and the Social Service Department for financial aid are also needed. It is recommended that the hospital should expedite the transfer process by prioritizing the cost and the information as medical expenses, knowledge of referring system and the information of the receiving hospital, are the most important factors to the willingness to transfer to a lower level of care.

• Radiation Oncology Journal
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• 제20권2호
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• pp.116-122
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• 2002

목적 : 국한성병기 소세포폐암의 교대 방사선-항암제 병행치료(alternating radio-chemotherapy)에서 방사선치료의 시기의 차이에 따른(조기 혹은 지연) 치료반응률, 생존율, 재발양상, 치료에 따른 부작용을 비교하기 위해 전향적 무작위 비교연구를 시행하였다. 대상 및 방법 : 1993년 8월부터 1996년 8월까지 국한성병기 소세포폐암으로 진단받은 환자들은 연세암센터에서 조기(early arm) 혹은 지연(delayed arm) 교대 방사선-항암제치료군으로 무작위 분류되었다. 총 56명의 환자 중 44명이 비교분석 되었다. 환자들의 특성은 양군간에 차이가 없었다. 교대 방사선-항암제치료는 항암제치료기간 중 방사선 치료를 쉬는 방법으로 교대로 쉬지 않고 치료를 하는 방법으로 조기방사선치료군(N=22)은 항암제 1차치료 후 방사선치료를 시작하였고 지연방사선치료군(N=22)은 3차 항암제치료후 방사선치료를 시작하였다. 방사선치료는 1.8 Gy/fr으로 54 Gy/30 fr을 조사하였고 항암제치료는 Ifosfamide $1.5\;g/m^2$, 정맥주사로 제1일에서 5일까지 투여하였고 Carboplatin AUC (area under the concentration-time eurve) 5/day, 정맥주사로 제 2일째 투여하였으며 4주 간격으로 총6회 시행하였다. 관해율은 방사선치료 종료 한달 뒤 판정하였고 부작용의 빈도와 정도는 RTOG 등급체계를, 생존율은 Kaplan-Meier 법을 사용하였고, 비교는 Log-rank test를 이용하였다. 결과 : 치료에 대한 반응률은 조기군 $86\%$, 지연군 $85\%$로 차이가 없었다. 전체환자의 2년 생존율은 $18.9\%$, 중앙생존기간 15개월이었다. 치료시기별 2년 생존율, 중앙생존기간은 조기군 $22.7\%$와 15개월, 지연군 $14.9\%$와 17개월로 통계적으로 유의한 차이가 없었다(p=0.47). 2년 무재발생존율은 조기군 $19.1\%$, 지연군 $19.6\%$로 차이가 없었다(p=0.52), 국소재발은 조기군 $43\%$, 지연군 $45\%$로 차이가 없었고, 원격전이는 조기군 $81\%$, 지연군 $70\%$으로 재발양상에서도 차이가 없었다. 첫 재발부위로 뇌전이는 조기군 $23\%$, 지연군 $35\%$로 차이가 없었다(p=0.51). 치료에 따른 부작용(RTOG 등급 $3\~4$)도 양군간에 차이가 없었다. 치료에 대한 순응도를 비교해볼 때 항암제치료를 6회 이상 시행받은 환자가 조기군 $82\%$, 지연군 $77\%$, 방사선치료를 45 Gy 이상 받은 환자가 조기군 $82\%$, 지연군 $91\%$로 양군간에 차이가 없었고 양군에서 대부분의 환자들은 치료에 잘 순응하였다. 결론 : 국한성병기 소세포폐암의 교대 방사선-항암제치료시 방사선치료를 조기 혹은 지연하여 시행하였을 때 치료 반응률, 생존율, 재발양상, 부작용에는 차이가 없었으며 교대 방사선-항암제치료에 대한 환자들의 순응도는 높았다.

• 대한두경부종양학회지
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• 제17권1호
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• pp.59-62
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• 2001

Objectives: We report an interim result of conformal radiotherapy in a patient with early stage cancer at the base of the tongue, which developed in a previously irradiated area. Materials and Methods: A 64-year-old male patient was diagnosed with T4N0M0 supraglottic cancer. He received 72Gy of radiation therapy from 21 November 1988 to 24 February 1989. He had local failure and underwent a salvage total laryngectomy on 28 August 1989. Subsequently, he did well. In early 1999, he suffered from throat pain. He had a 2.5cm ulcerative mass at the base of his tongue, in the area that had been irradiated previously. Biopsy showed squamous cell carcinoma. After workup, he was diagnosed with base of tongue cancer with T2N0M0. Surgery was not feasible because the morbidity was not acceptable. Since it was difficult to re-irradiate the area with a curable dose using conventional 2D radiation therapy with an acceptable morbidity, we decided to try conformal radiotherapy. We used 7 static beam ports with field sizes from $7x6.4\;to\;8x8cm^2$, using 6 and 10MV photons. The fractionation regimen was 1.8Gy, 5 times per week. He received 64.8Gy in 36 fractions from 9 April 1999 to 1 June 1999. Results: In the 21 months since radiotherapy, the patient has not experienced any acute or chronic complications, such as xerostomia. He experienced relief of pain shortly after the start of radiotherapy, showed a complete response, and is still doing well. Conclusion: Conformal radiotherapy can be used to treat cancer that develops within a previously irradiated field, with curative intent.

• 대한두경부종양학회지
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• 제19권1호
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• pp.9-15
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• 2003

Purpose: To introduce our early experience with intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma. Methods and Materials: Eight patients who underwent IMRT for no disseminated nasopharyngeal carcinoma at the Asan Medical Center between September 2001 and November 2002 were evaluate by prospective analysis. According to the 1997 American Joint Committee on Cancer staging classification, 5 had Stage III, and 3 had Stage IVB disease. The IMRT plans were designed to be delivered as a 'Simultaneous Modulated Accelerated Radiation Therapy' (SMART) using the 'step and shoot' technique with a MLC (multileaf collimator). Daily fractions of 2.2-2.5Gy and 1.9-2Gy were prescribed and delivered to the GTV and CTV and clinically negative neck node, respectively. The prescribed dose was 70A-79.0Gy to the gross tumor volume (GTV), 60Gy to the clinical target volume (CTV) and metastatic nodal station, and 46Gy to the clinically negative neck. All patients also received weekly cisplatin during radiotherapy. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Results: Follow-up period was ranging from 5 to 18 months. All patients showed complete response and loco-regional control rate was 100% but one patient died of malnutrition due to treatment related toxicity. There were no Grade 3 or 4 xerostomia and all patients had experienced improvement of salivary gland function. Conclusion: 'Simultaneous Modulated Accelerated Radiation Therapy' (SMART) boost intensity-modulated radiotherapy technique allows parotid sparing as evidenced both clinically and by dosimetry. Initial tumor response and loco-regional control was promising. It is clinically feasible. A larger population of patients and a long-term follow-up are needed to evaluate ultimate tumor control and late toxicity.

• Radiation Oncology Journal
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• 제19권4호
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• pp.301-305
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• 2001

목적 : 초기 성문암의 방사선치료에 있어 소분할 치료(hypofractionated radiation therapy)의 용이성과 그 부작용의 정도를 파악하고자 하였다. 대상 및 방법 : 1999년 2월부터 2000년 2월까지 서울대학교 병원 치료방사선과에 내원하여 조직학적으로 확진된 I, II 병기의 초기 성문암환자 20명을 대상으로 전향적 연구를 진행하였다. 환자군의 성별분포는 18명이 남자, 2명이 여자였으며, 연령의 중앙값은 59세였다. 병기의 분포는 T1aN0 - 16명, T1bN0 - 1명, T2N0 3명이었다. 18명의 환자는 후두미세수술을 통한 조직생검을 시행하였으며 2명의 환자는 레이저 절제술을 시행받았다. 모든 환자는 근치적 방사선치료를 2.5 Gy의 분할조사선량으로 총 50 Gy의 방사선을 24회 분할하여 시행받았다. 치료 기간의 중앙값은 36일 이었다(범위 $31\~45$일). 결과 : 방사선치료 기간 중 급성 반응으로 치료를 중단한 환자는 없었다. 주된 급성 부작용은 식도염과 애성이었으며 치료 후에는 호전되었다. RTOG grade 3의 식도염으로 인한 연하통을 보인 환자가 1례에서 있었고, 6례에서 grade 3의 애성을 보였다. 방사선치료에 대한 반응은 치료 종료 1개월 후에 판정하고 모든 환자에서 완전관해를 보였다. 20명의 환자 중 3명에서 재발이 관찰되었는데, 2례는 방사선치료 후 10개월과 13개월의 시점에서 국소재발이 관찰되었고, 1례는 방사선치료 후 2개월의 시점에서 경부 림프절에서의 재발이 관찰되었고 4개월 후 원격전이가 관찰되었다. 결론 : 소분할 방사선치료는 시행상의 큰 어려움 없이 진행되었으며 질병의 관해에 효과적인 것으로 나타났다. 하지만 방사선치료기간의 단축이 종양의 치료 결과에 미치는 영향과 만성 부작용을 파악하기 위해서 보다 오랜 기간의 추적 관찰이 필요할 것으로 생각된다.X>은 필름에 비해 2 mm 가량 크며, 최소 beamlet 크기가 5 mm 임을 감안할 때 부적합한 것으로 판명되었다. RTP commissioning 후 계산 선량은 $1\times1\;cm^2$ 크기 소조사면에서의 측정치와 $2\%$ 범위 내에서 일치하였다. C자 형태의 PTV에 대한 9개의 세기변조된 조사빔에 대한 2회에 걸친 치료중심점에서의 절대선량 측정결과 개별 조사빔에 대하여는 $10\%$ 이상 차이를 보였으나 총 선량은 $2\%$ 이내에서 일치하였다. 필름을 이용한 선량분포도도 계산치와 비교적 잘 일치하였다. 실제 치료환자의 팬톰 내에서의 절대선량 측정 결과 총 선량은 $1.5\%$ 차이를 보였다. 각 조사빔에 대해 중심 leaf의 측방선량분포도를 필름 및 선형배열다중검출기를 사용하여 측정하였으며, 조사면 밖에서 계산선량이 $2\%$ 내외로 작게 나타났으나, 특정 위치를 제외하고는 $3\%$ 이내로 잘 일치함을 확인하였다. 결론 : 세기조절방사선치료를 위해서는 다엽콜리메이터의 위치에 대한 보다 정밀한 정도관리 절차가 개발되어야 될 것으로 판단되며, 조사빔내 세기패턴을 효율적으로 확인할 수 있는 정도보증 절차가 필요할 것으로 사료된다. 본원에서는 팬톰 내에서의 치료중심점과 같이 특정 지점에서의 절대선량 확인 및 필름 혹은 선형배열다중검출기를 사용한 세기분포 패턴의 확인 과정을 통하여, 이를 적절히 병행하여 사용함으로써 세기조절방사선치료에 적합한 정도관리를 시행할 수 있었다.용하여 방광 보존을 및 5년 생존율에 있어 만족할 만한 결과를 얻었다. 완전한 TURBT와 유도 MCV 항암요법과 cisplatin 방사선 병용요법에서 완전관해 여부가 방광보존가능성과 생존율에 영향을 미치는 요소로 생각되고 만약 완전관해를

• Archives of Pharmacal Research
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• 제29권10호
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• pp.911-920
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• 2006

Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around $10\;{\mu}M$. This in vivo concentration might offer some insights for the many in vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, ${\gamma}-GCS$, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slco1b2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate the in vivo pharmacokinetics of BHA, the in vivo activation of MAPK signaling proteins, as well as the in vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제24권1호
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• pp.7-18
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• 2021

Purpose: The long-term efficacy and safety of infliximab (IFX) in children with ulcerative colitis (UC) have not been well-evaluated. Here, we reviewed the long-term durability and safety of IFX in our single center pediatric cohort with UC. Methods: This retrospective study included 20 children with UC who were administered IFX. Results: For induction, 5 mg/kg IFX was administered at weeks 0, 2, and 6, followed by every 8 weeks for maintenance. The dose and interval of IFX were adjusted depending on clinical decisions. Corticosteroid (CS)-free remission without dose escalation (DE) occurred in 30% and 25% of patients at weeks 30 and 54, respectively. Patients who achieved CS-free remission without DE at week 30 sustained long-term IFX treatment without colectomy. However, one-third of the patients discontinued IFX treatment because of a primary nonresponse, and one-third experienced secondary loss of response (sLOR). IFX durability was higher in patients administered IFX plus azathioprine for >6 months. Four of five patients with very early onset UC had a primary nonresponse. Infusion reactions (IRs) occurred in 10 patients, resulting in discontinuation of IFX in four of these patients. No severe opportunistic infections occurred, except in one patient who developed acute focal bacterial nephritis. Three patients developed psoriasis-like lesions. Conclusion: IFX is relatively safe and effective for children with UC. Clinical remission at week 30 was associated with long-term durability of colectomy-free IFX treatment. However, approximately two-thirds of the patients were unable to continue IFX therapy because of primary nonresponse, sLOR, IRs, and other side effects.

• Pediatric Infection and Vaccine
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• 제29권1호
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• pp.28-36
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• 2022

목적: 5-11세 소아에서 코로나19 백신의 효능과 안전성을 평가하기 위해서 체계적 문헌고찰을 시행하였다. 방법: 2022년 1월 4일까지 Ovid-MEDLINE 및 medRxiv를 검색하여 문헌을 선정하고 자료를 추출하였다. 근거 수준을 평가하기 위해 GRADE 도구를 사용하였다. 결과: 총 1,675 건의 연구가 일차적으로 검색되었고 최종적으로 5편의 연구가 포함되었다. 서로 다른 4개의 코로나19 백신(BNT162b2, mRNA-1273, CoronaVac, BBIBP-CorV)에 대한 무작위 대조군 연구 결과들은 5-11세 연령에서 각 백신의 양호한 면역원성과 안전성을 보여주었다. 미국에서 5-11세 소아 연령에서 BNT162b2 백신 접종 후 이상사례 모니터링 연구에서는 승인 전 임상시험을 통해 예상되었던 국소반응 및 전신반응이 보고되었으나 중대한 이상사례는 거의 보고되지 않았다. 결론: 5-11세 연령에서 코로나19 백신 접종에 대한 데이터는 제한적이다. 이 연령에서 코로나19 백신의 안전성과 효과에 대한 체계적인 평가를 위해 지속적이고 포괄적인 모니터링이 필요할 것으로 보인다.

• Pediatric Infection and Vaccine
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• 제23권1호
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• pp.25-30
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• 2016

목적: 가와사끼병에서 C-반응 단백질(CRP)과 적혈구 침강속도(ESR)의 불일치 및 정맥내 면역글로불린(IVIG) 치료 후의 변화를 보고자 하였다. 방법: 총 123명의 가와사끼병 환자의 의무기록를 후향적으로 분석하였다. 염증성 지표들을 IVIG 치료 전과 치료 후 48-72시간에 검사하였다. 불일치는 $CRP{\geq}10mg/dL$와 ESR <50 mm/hr, 또는 CRP <10 mg/dL와 $ESR{\geq}50mm/hr$로 정의하였고 전자를 1 군으로, 후자를 2군으로 구분하였다. 결과: 전체 123명 중 36명(29.2%)에서 불일치를 보였는데 1군은 25명(20.3%)이었고, 2군은 11명(8.9%)이었다. 1군에서 15명은 발열기간이 5일 미만(초기 발현자)이었고, 10명은 5일 이상(후기 발현자)이었다. 2군에서는 6명이 초기 발현자, 5명이 후기 발현자였다. ESR 값은 초기 발현자보다 후기 발현자에서 더 높았다($26.3{\pm}19.3mm/hr$ vs. $34.3{\pm}21.0mm/hr$, P=0.029). IVIG 치료 후에는 증가된 CRP를 포함한 여러 염증성 지표들은 정상으로 돌아왔으나 ESR은 오히려 $37.4{\pm}21.9mm/hr$에서 $48.0{\pm}22.7mm/hr$로 증가하였다(n=36, P=0.051). 결론: CRP와 ESR 값의 불일치는 발열기간과 연관이 있으리라 추정된다. 이 두 중요 염증성 지표가 불일치할 수 있으므로 급성 가와사끼병의 치료 전 질병의 염증 활성도를 평가하기 위해서는 이 두 지표를 동시에 검사하는 것이 필요하며, IVIG 치료 후의 ESR은 치료 반응의 지표로 적합하지 않다.