우유 단백질 유발성 장염 증후군의 병리 기전으로 세포 자멸사와 TNF-${\alpha}$, TRAIL receptor 1 (DR4)의 발현 증가

황진복,김상표,강유나,이성룡,서성일,권택규,Hwang, Jin-Bok,Kim, Sang-Pyo,Kang, Yu-Na,Lee, Seong-Ryong,Suh, Seong-Il,Kwon, Taeg-Kyu 대한소아청소년과학회 2010 Clinical and Experimental Pediatrics (CEP) Vol.53 No.4

목 적: 융모 위축을 보이는 FPIES 환자의 소장 점막에는 TNF-${\alpha}$의 발현이 증가한다. TNF-${\alpha}$는 상피 세포의 세포 자렴사를 유발하는 것으로 알려져 있다. 저자들은 FPIES 병리생리의 특성을 알아보고자 십이지장 점막 조직에서 TNF family와 TNF-수용체 family의 세포 자멸사를 연구하였다. 방 법: 표준화된 경구 유발 시험을 통하여 FPIES로 진단된 15례의 환자와 5례의 대조군을 대상으로 연구하였다. 세포 자멸사를 확인하기 위하여 terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) 염색을 시행하였다. 세포 자멸의 기전을 알아 보기 위해 TNF family의 TNF-${\alpha}$, Fas ligand (FasL)와 TNF-수용체 family의 TNF-related apoptosis-including ligand (TRAIL) receptor 1 (DR4), TRAIL receptor 2 (DR5), Fas를 면역조직화학으로 염색하였다. 결 과: $TUNEL^+$ 세포는 대조군에 비하여 FPIES 환자군의 십이지장 점막에서 의미 있게 높게 발현하였다($P$=0.043). TNF-${\alpha}$ ($P$=0.0001)와 DR4 ($P$=0.003)도 대조군에 비하여 FPIES군에서 의미 있게 높게 발현하였다. FasL, Fas, DR5의 발현은 두 군 모두에서 낮았으며, 두 군간에 의미 있는 차이를 보이지도 않았다. 결 론: FPIES의 병리생리는 세포 자멸사에 의하여 발생하며, TNF-${\alpha}$의 발현과 DR4 경로가 세포 자멸사에서 중요한 역할을 하는 것으로 추정된다. Purpose : Expression levels of tumor necrosis factor (TNF)-${\alpha}$ expression on the mucosa of the small intestine is increased in patients with villous atrophy in food protein-induced enterocolitis syndrome (FPIES). TNF-${\alpha}$ has been reported to induce apoptotic cell death in the epithelial cells. We studied the TNF family and TNF-receptor family apoptosis on the duodenal mucosa to investigate their roles in the pathogenesis of FPIES. Methods : Fifteen infants diagnosed as having FPIES using standard oral challenge test and 5 controls were included. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining was performed to identify the apoptotic cell death bodies. Immunohistochemical staining of TNF-${\alpha}$, Fas ligand (FasL) for TNF family and TNF-related apoptosis-including ligand (TRAIL) receptor 1 (DR4), TRAIL receptor 2 (DR5), and Fas for TNF-receptor family were performed to determine the apoptotic mechanisms. Results : $TUNEL^+$ was significantly more highly expressed in the duodenal mucosa of FPIES patients than in controls ($P$-0.043). TNF-${\alpha}$ ($P$=0.0001) and DR4 ($P$=0.003) were significantly more highly expressed in FPIES patients than in controls. Expression levels of FasL, Fas, and DR5 were low in both groups and were not significantly different between the 2 groups. Conclusion : These results suggest that FPIES pathogenesis is induced by apoptosis, and that TNF-${\alpha}$ expression and DR4 pathway may have an important role in apoptosis.

Is This Symptom Even a Food Allergy?: Clinical Types of Food Protein-induced Enterocolitis Syndrome

황진복 대한소아소화기영양학회 2014 Pediatric gastroenterology, hepatology & nutrition Vol.17 No.2

Food protein-induced enterocolitis syndrome (FPIES) is an under-recognized non-IgE-mediated gastrointestinal food allergy. The diagnosis of FPIES is based on clinical history, sequential symptoms and the timing, after excluding other possible causes. It is definitively diagnosed by an oral food challenge test. Unfortunately, the diagnosis of FPIES is frequently delayed because of non-specific symptoms and insufficient definitive diagnostic biomarkers. FPIES is not well recognized by clinicians; the affected infants are often mismanaged as having viral gastroenteritis, food poisoning, sepsis, or a surgical disease. Familiarity with the clinical features of FPIES and awareness of the indexes of suspicion for FPIES are important to diagnose FPIES. Understanding the recently defined clinical terms and types of FPIES is mandatory to suspect and correctly diagnose FPIES. The aim of this review is to provide a case-driven presentation as a guide of how to recognize the clinical features of FPIES to improve diagnosis and management of patients with FPIES.

What is the 'objective' differential factor of diarrhea in infancy?: Normal state versus diarrheal illness in infants with chronic frequent and loose stool

황진복,강경지,이중정,김애숙 대한소아청소년과학회 2010 Clinical and Experimental Pediatrics (CEP) Vol.53 No.12

Purpose: This study aimed to identify 'objective' differential factors for normal frequent loose stool (NFLS) and diarrheal illness with dehydration and nutritional deficiency (DIDN) among infants with chronic frequent loose stool (CFLS). Methods: Data were analyzed from infants under 2 years of age with CFLS who had been transferred from general pediatricians. These 46patients were divided into 2 groups (NFLS versus DIDN). Nocturnal stool was defined as evacuation between 10 pm and 6 am. Maximal stool amount/day (measured using the mother's hand) was specified as the highest score during the period of CFLS obtained by adding up each evacuation's score (range, 0-2 points). Results: There were 36 cases of NFLS and 10 of DIDN. A failure to gain weight (P=0.0001), fever (P=0.0079), colic/abdominal pain (P=0.0014), gross blood in stool (except allergic proctocolitis) (P=0.0113), nocturnal stool (P=0.0001), and the score of stool amount (P =0.0001) were found to significantly differentiate the groups. A failure to gain weight was observed in 39% of even NFLS. The frequency,mucus content, and microbiological findings of stools, as well as diaper dermatitis were not found to significantly differentiate the groups. Conclusion: NFLS was more common than DIDN in infants with CFLS. The most 'objective' differential factors were nocturnal stool and the score of stool amount (≥7 points/day).

영유아 만성설사의 감별 진단을 위한 객관적 설사의 정의

황진복 대한의사협회 2012 대한의사협회지 Vol.55 No.6

Among infants and toddlers with chronic frequent loose stool, normal frequent and loose stool (NFLS) is more common than diarrheal illness with dehydration and nutritional deficiency (DIDN). To identify more objective factors for differentiating between NFLS and DIDN is important. The frequency, mucus content, and microbiological findings of stools, as well as diaper dermatitis are not important factors to significantly differentiate the groups. Instead, a failure to gain weight, fever, colic/abdominal pain, gross blood in stool (except allergic proctocolitis),nocturnal stool, and the score of the stool quantity are important factors to significantly differentiate the groups. A failure to gain weight is also observed even in NFLS, which may come from iatrogenic diet manipulation with nutritionally deficient food. The most objective differential factors are nocturnal stool and the score of stool amount (≥7 points/day). The use of these objective factors could lessen parental anxiety and distress, iatrogenic undernutrition of patients,and socioeconomic loss due to improper medical investigations or inappropriate management of NFLS.

영유아 식품알레르기의 임상적 조망

황진복,Hwang, Jin-Bok 대한소아소화기영양학회 2011 Pediatric gastroenterology, hepatology & nutrition Vol.14 No.2

Food allergies affect 7~8% of infants and young children, and their prevalence appears to have increased in recent years. Food allergy refers to an abnormal immunological reaction to a specific food. These reactions can be recurrent each time the food is ingested. Food allergy manifests itself with a wide spectrum of clinical characteristics including IgE-mediated diseases as immediate reactions, non-IgE-mediated disorders as delayed reactions, and mixed hypersensitivities. As a consequence, the clinical picture of a food allergy is pleomorphic. A well-designed oral food challenge is the most reliable diagnostic test for infants and young children whose clinical history and physical examination point towards a specific food allergy. Food specific IgE antibody tests (RAST, MAST, skin prick test, Uni-CAP, etc) are an alternative tool to determine oral food challenge for IgE-mediated disorders, but not for non-IgE-mediated allergies. Moreover, parents often impose their children on unnecessary diets without adequate medical supervision. These inappropriate dietary restrictions may cause nutritional deficiencies. This review aims to introduce clinical perspectives of food allergy in infants and young children and to orient clinicians towards different strains of diagnostic approaches, dietary management, and follow-up assessment of tolerance development.

새로운 분류법에 따른 소아 위장관 우유 알레르기 질환에 관한 임상적 고찰

황진복,최선윤,권태찬,오훈규,감신,Hwang, Jin Bok,Choi, Seon Yun,Kwon, Tae Chan,Oh, Hoon Kyu,Kam, Sin 대한소아소화기영양학회 2004 Pediatric gastroenterology, hepatology & nutrition Vol.7 No.1

목 적: 효율적인 진단과 치료 및 적절한 의학적 교류를 목적으로 소아 위장관 알레르기 질환의 새로운 분류법이 발표되었다(J Pediatr Gastroenterol Nutr 2000;30:S87-94). 그러나 명칭과 분류의 변경으로 이미 알려진 질환들이 새로운 질환으로 보고되기도 하는데, 저자들은 새로운 분류법에 따른 소아 위장관 알레르기 질환의 질병군에 관하여 알아보고, 국내에서 이미 보고된 관련 문헌을 함께 고찰하여 의학적 교류에 혼선을 최소화 하고자 한다. 방 법: 2003년 3월부터 7월까지 계명대학교 의과대학 소아과를 방문하여, 우유 유발 및 제거시험, 내시경을 이용한 조직생검 등을 이용하여 소아 GI-CMA로 진단된 37례(남 19, 여 18)를 대상으로 후향성 조사하였다. 새로운 분류에는 포함되지 않았으나 위식도역류 관련 알레르기를 추가하였다. 국내 문헌은 소아과학회지, 소아소화기영양학회지, 소아알레르기호흡기학회지를 근거로 고찰하였다. 결 과: 1) 대상 환아의 연령은 2주~15개월, 평균 $5.4{\pm}4.8$개월이었다. 2) 출생체중은 전례에서 10~90백분위수를 차지하였으며, 25~75백분위수가 25례(68%)를 차지하였다. 내원 당시 체중은 3백분위수 이하가 18례(49%)이었다. 3) 증상발현에서 진단까지 걸린 시간은 2주~12개월, 평균 $2.4{\pm}3.3$개월이었다. 4) IgE 군인 IgE 매개형 우유알레르기(IGE) 6례(16%), IgE와 Non-IgE 혼합군인 호산구성 위장관염(EOS) 2례(5%), Non-IgE군인 전형적 우유 단백질 유발 장관염(CMPIE-T) 7례(19%), 비전형적 우유 단백질 유발 장관염(CMPIE-AT) 5례(14%), 알레르기성 대장염(AC) 12례(32%)이었다. 위식도역류증 관련 우유 알레르기(GERA)는 5례(14%)이었다. CMPIE-T 전례에서 소장 조직생검상 장병증이 관찰되었다. 5) 진단 당시 연령은 IGE $4.3{\pm}0.8$개월, EOS 생후 2주와 14개월, CMPIE-T $3.8{\pm}4.6$개월, CMPIE-AT $10.4{\pm}3.8$개월, AC $3.4{\pm}3.9$개월, GERA $7.8{\pm}5.7$개월로 질환군간 유의한 차이를 보였다(p<0.05). 6) 내원 당시 3백분위수 이하를 보인 경우가 IGE 17%, EOS 0%, CMPIE-T 86%, CMPIE-AT 60%, AC 25%, GERA 100%로 질환군간 유의한 차이를 보였다(p<0.05). 7) 국내 문헌을 고찰하여 소아 위장관 우유 알레르기 질환은 만성설사, 난치성설사, 우유 불내성, 우유 알레르기, 위장관 알레르기, 우유 과민성 장병증, 호산구성 위장관염, 알레르기성 대장염 등의 용어로 보고되었다. 결 론: 새로운 분류법에 따른 소아 위장관 우유 알레르기 질환은 연령, 임상 증상, 위장관 침범 부위에 따라 특징적인 유형으로 구분할 수 있으며, 임상적으로 드물지 않다. 국내의 문헌을 통하여 다양한 용어로 각 유형의 알레르기 질환들은 연구 보고되어 왔다. Purpose: A new classification of gastrointestinal food allergy was published, but the changes of terminology between previously reported terms and the new ones were in a state of disorder. This has resulted in confusion between medical communication and diagnostic and therapeutic approaches. The clinical observations of infants presenting with gastrointestinal cow milk allergy (GI-CMA) were performed, and the changes in the terminology reviewed through the published Korean literature. Methods: Between March 2003 and July 2003, data from 37 consecutive infants with GI-CMA, aged 2 weeks to 15 months, were reviewed. The challenge and elimination test of cow milk, and the endoscopic and histologic findings, were used for the seven subdivisions of GI-CMA according to a new classification on the basis of patients' ages, clinical manifestations and location of gastrointestinal lesions. Results: The 37 patients had a mean age of $5.4{\pm}4.8$ months, with those observed in 26 (70.3%) of patients being below 6 months of age. The seven final diagnoses were; cow milk protein-induced enterocolitis (CMPIE) in 12 (32.4%), cow milk protein proctitis (PROC) in 12 (32.4%), IgE-mediated (IGE) in 6 (16.2%), gastroesophageal reflux-associated cow milk allergy (GERA) in 5 (13.5%) and eosinophilic gastroenterocolitis in 2 (5.4%). CMPIE was revealed as the typical type in 7 (18.9%) and the atypical type in 5 (13.5%), and all of typical CMPIE revealed cow milk protein-induced enteropathy. The mean age at symptom onset was $4.3{\pm}0.8$ months, and for those with typical and atypical CMPIE, and PROC and GERA were $3.8{\pm}4.6$, $10.4{\pm}3.8$, $3.4{\pm}3.9$ and $7.8{\pm}5.7$ months, respectively (p<0.05). The period from onset of symptom to diagnosis was $2.4{\pm}3.3$ (0.5~12) months, with those observed in atypical CMPIE and GERA being over 3months. Although the birth weights in all patients were within the 10~90 percentile range, the body weights on diagnoses were below the 3 percentile in 48.6%; IGE 16.7%, EOS 0%, typical CMPIE 85.7%, atypical CMPIE 60.0%, PROC 25.0% and GERA 100% (p<0.05). Through the review of the Korean literature, 8 case reports and 14 original articles for GI-CMA were found. Conclusion: GI-CMA is not a rare clinical disorder and is subdivided into seven categories on the basis of the patient's age, clinical manifestations and location of the gastrointestinal lesions. The terms for GI-CMA are changing with new classifications, and careful approaches are necessary for medical communications.

효과적인 의학 논문 작성을 위한 요령

황진복,Hwang, Jin-Bok 대한소아소화기영양학회 2010 Pediatric gastroenterology, hepatology & nutrition Vol.13 No.2

This paper aims to give beginners an introductory course on how to write a medical paper more effectively. Bear in mind the reviewer and the reader will be reading your paper for the first time, so you should write it easily. Everything in your paper must be coherent. Use of the active voice is usually shorter and clearer. Organize your story carefully and logically, and then you can avoid unnecessary repetition in different sections. Think hard, because research is made by the mind, not by the hands. Write technically and powerfully. Above all, you have to meet the submission regulation of the target journal exactly.

The Significance of Gastric Juice Analysis for a Positive Challenge by a Standard Oral Challenge Test in Typical Cow’s Milk Protein-Induced Enterocolitis

황진복,Jeong Yoon Song,강유나,김상표,서성일,감신,Won Joung Choi 대한의학회 2008 Journal of Korean medical science Vol.23 No.2

This study was performed to investigate the significance of gastric juice analysis (GJA) as a diagnostic criterion of a positive challenge in a standard oral cow’s milk challenge (OCC) to confirm typical cow’s milk protein-induced enterocolitis (CMPIE). Data from 16 CMPIE patients (aged 14 to 44 days) were analyzed. A standard OCC was openly executed using 0.15 g/kg of protein. Three symptoms (vomiting, lethargy, and bloody or pus-like stool), and four laboratory findings (GJA [3 hr], changes in peripheral blood absolute neutrophil count [ANC] [6 hr], C-reactive protein [6 hr], and stool smear test for occult blood or leukocytes) were observed after OCC. Before OCC, baseline studies were conducted; a stool smear test, blood sampling, and GJA. Positive OCC results were; vomiting (87.5%) (observed 1-3 hr after OCC), lethargy (62.5%) (1-3 hr), bloody or pus-like stool (43.8%) (6-10 hr), abnormal GJA (93.8%), an ANC rise >3,500 cells/ L (93.8%), and an abnormal stool smear test (75.0%). A single GJA test after a standard OCC is a sensitive diagnostic criterion of a positive challenge, and may provide an early confirmatory diagnosis of CMPIE. An investigation of positive OCC outcomes helps to find out a diagnostic algorithm of criteria of a positive challenge in CMPIE.

주기성 구토증(cyclic vomiting syndrome)의 장기 추적 관찰 -이형 편두통(migraine variant)으로의 이행 과정인가?-

황진복,오희종,최광해,Hwang, Jin-Bok,Oh, Hee-Jong,Choi, Kwang-Hae 대한소아소화기영양학회 2000 Pediatric gastroenterology, hepatology & nutrition Vol.3 No.1

저자들은 주기성 구토증으로 진단된 3명의 소아에서 6년 이상의 장기 추적관찰을 통하여 임상양상의 다양한 변화과정을 관찰하여 보고, 뇌파검사의 이상소견을 근거로 이형 편두통의 형태로 진행하여 가는 과정을 관찰하였다. 시간의 경과에 따라 구토 발병 주기, 기간의 변화와 함께 위배출능 저하, 두통의 발현, 뇌파의 이상 등 다양한 임상 양상의 변화를 보여주며, 2례에서는 증상의 소실이 관찰되었다. 특히, 뇌파 검사상 증상 발현시 발생하는 서파는 편두통의 발생 직전에 뇌혈류의 감소로 발생하는 양상과 매우 유사하며, 주기성 구토증과 편두통의 관련성을 시사하여 주는 소견으로, 진단 및 치료적 접근시 반드시 고려하여야 한다. 주기성 구통증은 이형 편두통으로의 이행 과정인가? Cyclic vomiting syndrome(CVS) is a disorder of unknown etiology that is characterized by its clinical pattern of intermittent episodes of severe vomiting, similar in time of onset and duration, with no symptoms during the intervening period. By definition, CVS is an idiopathic disorder that requires exclusionary laboratory testing. Not only can it be mimicked by many specific disorders, eg, surgical, neurologic, endocrine, metabolic, renal, but within idiopathic CVS there may be specific subgroups that have different mechanisms. It has been reported that CVS usually begins in toddlers and resolves during adolescence. Migraine is also self-limiting episodic condition of children and the clinical features of migraine and CVS show considerable similarity. It is proposed that CVS is a condition related to migraine. This paper reports clinical courses of long term follow-up and reversible EEG changes in three patients whose history included CVS. Clinical situations of attack interval, duration and associated symptoms had changed variablely in each patients through long term follow-up period. Cyclic vomiting subsided in two cases. Abnormal delta activity was seen during episodes and resolved at follow-up, when the patient asymptomatic. The brain wave changes support the interpretation of CVS as a migraine variant.

내독소로 활성화된 호중구가 폐포모세혈관 내피세포에 미치는 영향

황진복,신현호,이경호,손윤경,서인수 慶北大學校 醫科大學 1991 慶北醫大誌 Vol.32 No.4

내독소에 의한 폐상해에서 호중구와 폐포 모세혈관 내피세포의 상호 작용에 대하여 알아보기 위하여 저자는 실험동물을 폐동맥을 통하여 폐포 모세혈관을 미리 관류 세척한 후 체외에서 내독소로 활성화시킨 호중구와 활성화시키지 않은 호중구를 폐동맥으로 관류시켜 투여한 실험군과 폐포 모세혈관을 관류 세척한 후 폐동맥으로 내독소로 주사하여 내피세포를 미리 전처치한 다음 활성화시킨 호중구 및 활성화시키지 않은 호중구를 주입한 실험군 등으로 나누어 실험하였다. 각 군의 실험동물들은 실험이 완료된 후 생리식염수로 1시간 동안 관류한 다음 폐를 적출하여 광학현미경 및 전자현미경으로 관찰하였다. 성적을 요약하면 폐포 모세혈관을 세척한 후 폐동맥으로 내독소를 먼저 주사하여 내피세포를 전처치한 후 다음 체외에서 내독소로 활성화시킨 호중구를 폐동맥으로 투여한 실험군에서 현저하게 많은 수의 호중구가 폐포 모세혈관내벽에 유착이 일어나 있었으며 폐포 간질내의 호중구 은둔도 있었다. 그리고 전반적인 폐조직의 형태학적 변화가 현저하게 초래되었으며 폐포 탐식구의 증가도 뚜렷하였다. 내독소로 내피세포를 전처치시키지 않고 체외에서 내독소에 의하여 활성화된 호중구를 투입한 실험군과 관류세척 후 폐동맥으로 내독소를 먼저 주입하여 내피세포를 전처치한 다음 내독소로 활성화시키지 않은 호중구를 투여한 실험군 모두에서 폐포 모세혈관내에 호중구의 유착과 폐포 간질내로의 호중구 은둔도 곤찰되었다. 그러나 내피세포를 내독소로 전처치하지 않고 역시 내독소에 위하여 활성화를 시키지 않은 호중구를 투여한 실험군에서는 폐포 모세혈관내 호중구가 거의 관찰되지 않았고 폐포 간질내로의 은둔도 볼 수 없었다. 이상의 성적으로 미루어 내독소는 호중구와 폐포 모세혈관 내피세포에 모두 작용하여 폐포 모세혈관에서의 호중구의 유착과 폐포 간질내의 호중구 은둔을 일으키며, 이러한 호중구의 활성화가 내독소에 의한 폐부종의 원인이 될 것으로 생각된다. The authors studied the interactions between neutrophils and alveolar capillary endothelial cells on the endotoxin induced pulmonary injury. The experimental groups were listed below; group 1, inactivated neutrophils were injected through pulmonary artery after perfusion washing of the lung; group 2, activated neutrophils were administered after perfusion washing of the lung; group 3, endotoxin was administered through pulmonary artery after perfusion washing of the lung for the purpose of endotoxin pretreatement of pulmonary endothelial cells and then inactivated neutrophils were injected; group 4, endotoxin pretreatement of pulmonary endothelial cells and then activated neutrophils were injected. The lungs of experimental animals were extracted 1 hour after neutrohil injection and examined by light and electron microscopes. The results obtained were summarized as follows: In the group 4(endothelial-pretreated and activated neutrophil injected group), marked intracapillary adherence and interstitial sequestration of neutrophils was noted. Deterioration of alveolar structure and increase of alveolar macrophages was also present. Both in the group 2(activated neutrophil injected group) and group 3(endothelial-pretreated group) intracapillary adherence and neutrophils sequestration was seen. The lungs of group 1 revealed no remarkable change without neutrophilic adherence or sequestration. These results suggested that the mechanism of plumonary sequestration of ARDS may be due to activation and/or modification of both neutrophils and alveolar capillary endothelial cells in endotoxemia. The activated neutrophils act as an important on the endotoxin induced pulmonary edema.