• Title/Summary/Keyword: Liver, disease

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Ceftriaxone Associated Biliary Pseudolithiasis (Ceftriaxone 사용후 발생된 Pseudolithiasis)

  • Kim, Jae-Young;Ko, Jae-Sung;Lee, Hwan-Jong;Ko, Young-Ryul;Seo, Jeong-Kee
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.1 no.1
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    • pp.100-106
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    • 1998
  • Purpose: Ceftriaxone, a potent parenteral third-generation semisynthetic cephalosporin is widely used for the treatment of a variety of bacterial infections in both children and adult. Review of recent data indicates that ceftriaxone treatment has been associated with the development of reversible biliary pseudolithiasis and that is thought by many to be a benign process. Despite, several reports describe patients with ceftriaxone pseudolithiasis who required cholecystectomy for presumed acute cholecystitis. In this study we evaluated the incidence, risk factors, and prognosis of gallbladder pseudolithiasis after ceftriaxone treatment. Methods: Between march, 1997 and January, 1998, any child admitted to the Children's hospital of National University of Seoul and prescribed ceftriaxone for probable or definite bacterial infection were eligible for the study. 21 of them had ultrasound examination on the 2~12 days later after the start of ceftriaxone treatment, 8 of whom documented gallbladder precipitates or pseudolithiasis during treatment by serial abdominal ultrasound. Repeat abdominal ultrasound was performed 10~80 days later after the end of ceftriaxone treatment. The children with underlying liver disease or decreased renal function were excluded in this study. Results: 1) 21 children had ultrasound examinations of gallbladder during ceftriaxone treatment and 8 (38%) of them acquired pseudolithiasis. 2) The patients who developed gallbladder pseudolithiasis were significantly older ($6.3{\pm}2.9$ yr. vs $2.2{\pm}3.1$ yr.)(p<0.05), and older than 24 months were probably the significant risk associated with this phenomenon (p<0.05). However, no significant differences in sex, type of infection, fasting, and ceftriaxone treatment regimen (dose, duration of therapy). 3) The abnormality found on gallbladder ultrasonography was a strikingly hyperechogenic material with post-acoustic shadowing in 5 patients without post-acoustic shadowing in 3 patients 4) Follow up of gallbladder ultrasound was performed in 6 patients after cessation of ceftriaxone treatment. Sonographic abnormalities completely resolved within 14 days post cessation of therapy in 2 patients; 30 days, 1 patient; 80 days, 3 patients. Conclusions: We suggest that routine abdominal ultrasound should be considered in all children who received high dose ceftriaxone in more than 24 months of age and developed hepatobiliary symptoms during or just after ceftriaxone treatment.

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Radiation Therapy for Bone Metastases from Hepatocellular Carcinoma: Effect of Radiation Dose Escalation (간세포암에 의한 뼈전이의 방사선치료: 고선량 방사선치료의 효과)

  • Kim, Tae-Gyu;Park, Hee-Chul;Lim, Do-Hoon;Kim, Cheol-Jin;Lee, Hye-Bin;Kwak, Keum-Yeon;Choi, Moon-Seok;Lee, Joon-Hyoek;Koh, Kwang-Cheol;Paik, Seung-Woon;Yoo, Byung-Chul
    • Radiation Oncology Journal
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    • v.29 no.2
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    • pp.63-70
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    • 2011
  • Purpose: To evaluate the extent of pain response and objective response to palliative radiotherapy (RT) for bone metastases from hepatocellular carcinoma according to RT dose. Materials and Methods: From January 2007 to June 2010, palliative RT was conducted for 103 patients (223 sites) with bone metastases from hepatocellular carcinoma. Treatment sites were divided into the high RT dose and low RT dose groups by biologically effective dose (BED) of 39 $Gy_{10}$. Pain responses were evaluated using the numeric rating scale. Pain scores before and after RT were compared and categorized into 'Decreased', 'No change' and 'Increased'. Radiological objective responses were categorized into complete response, partial response, stable disease and progression using modified RECIST (Response Evaluation Criteria In Solid Tumors) criteria; the factors predicting patients' survival were analyzed. Results: The median follow-up period was 6 months (range, 0 to 46 months), and the radiologic responses existed in 67 RT sites (66.3%) and 44 sites (89.8%) in the high and low RT dose group, respectively. A dose-response relationship was found in relation to RT dose (p=0.02). Pain responses were 75% and 65% in the high and low RT dose groups, respectively. However, no statistical difference in pain response was found between the two groups (p=0.24). There were no differences in the toxicity profiles between the high and low RT dose groups. Median survival from the time of bone metastases diagnosis was 11 months (range, 0 to 46 months). The Child-Pugh classification at the time of palliative RT was the only significant predictive factor for patient survival after RT. Median survival time was 14 months under Child-Pugh A and 2 months under Child-Pugh B and C. Conclusion: The rate of radiologic objective response was higher in the high RT dose group. Palliative AT with a high dose would provide an improvement in patient quality of life through enhanced tumor response, especially in patients with proper liver function.

An Epidemiologic Study of Metastatic Bone Tumor (전이성 골종양의 역학적 연구)

  • Kim, Jae-Do;Lee, Duk-Hee;Park, Jeong-Ho;Son, Young-Chan;Hong, Yonng-Gi;Son, Jeong-Hwan
    • The Journal of the Korean bone and joint tumor society
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    • v.1 no.1
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    • pp.38-44
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    • 1995
  • Metastatic bone tumor is the most common bone tumor and 32.5% of all primary malignant tumors are eventually metastasize to bone. Metastatic bone tumor has been more frequently encountered disease in the orthopedic fields due to the greater longevity of life of the patients with primary visceral cancers by major advances in early detection, diagnosis, and surgical/radiotherapeutic/chemotherapeutic treatment of primary and metastatic lesions. Therefore, the epidemiologic data about the incidences and the patterns of bone metastasis is important. We reviewed 417 patients who were diagnosed and treated for metastatic bone tumor at Kosin University Medical Center from 1985 to 1993 to analyse the primary lesion, age and sex distributions, location of bone metastasis, patterns of metastasis according to the primary. The results were as follows : 1. The common origin of bone metastasis were lung(29.5%), stomach(15.3%), breast(11.3%), unknown(7.7%), cervix(5.3%), liver(4.8%) in order of frequency. 2. There were 251 men and 166 women and their mean age was 54.8 years and the peak age incidence was in 6th decades. Most cases(85.3%) were occured beyond 5th decades. 3. The preferred sites of metastatic deposits were spine(64.0%), pelvis(40.5%), rib(38.8%), femur(36.7%), skull(21.1%), humerus(13.9%), scapula(13.0%) in order of frequency. In the spine, thoracic(42.1%), lumbar(39.1%), cervical(13.2%), sacral(5.6%) vertebrae were involved in order of frequency. 4. Multiple bone metastases were more common(73.1%) than single metastasis(26.9%). 5. In the lung cancer, the peak age incidence was 6th decades, and the preferred sites of bone metastasis were spine, pelvis, femur. 6. In the stomach cancer, the peak age incidence was 6th decades, and the preferred sites of bone metastasis were spine, femur, pelvis. 7. In the breast cancer, the peak age incidence was 5th decades, and the preferred sites of bone metastasis were spine, rib, pelvis. 8. In the bone metastasis with unknown primary site, the peak age incidence was 7th decades, the preferred sites of bone metastasis were spine, femur, pelvis, and the common histologic types were adenocarcinoma and squamous cell carcinoma.

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Anti-Thrombogenic and Anti-Inflammatory Effects of Solvent Fractions from Leaves of Zanthoxylum Schinifolium (Sancho Namu) in Rats Fed High Fat Diet (고지방식이 흰쥐에서 산초나무 Butanol 및 Methylene Chloride 분획의 항혈전 및 항염증 작용)

  • Jang, Hyun-Seo;Rhee, Soon-Jae;Woo, Mi-Hee;Cho, Sung-Hee
    • Journal of Nutrition and Health
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    • v.40 no.7
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    • pp.606-615
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    • 2007
  • This study was performed to investigate anti-thrombogenic, anti-inflammatory effects of n-BuOH (B) and $CH_2Cl_2$ (MC) fractions extracted from Sancho (Zanthoxylum. schinifolium) leaves in rats fed high fat diets. The experimental animal groups were consisted of eight including one 5% fat (N) and one 20% fat (H) without the test materials in diets and six H groups of feeding three levels (50, 100 and 150 mg/day) of the B and the MC fractions from Z. schinifolium, respectively. Plasma activated partial thromboplastin times and thrombin times of H group were decreased compared to the N group, but they were increased by feeding the MC fraction of 50 mg and over. Polymorphonuclear leukocyte 5#-lipo-xygenase activities and leukotriene $B_4$ contents of the H group were significantly increased compared to the N group, but they were decreased in the 100 mg and 150 mg of B fraction or the 150 mg of MC fraction fed groups. Liver cytochrome $P_{450}$, $O_2^-$, $H_2O_2$ and GSSG contents were increased by the high fat diet but decreased by feeding the B fraction or the MC fraction, while GSH content and glutathione S-transferase activity lowered by high fat diet were increased by feeding the two solvent fractions. The effects of the solvent fractions were evident at the level of 100 mg/day and over. The present results confirmed that two solvent fractions from the leaves of Z, schinifolium have enhancing effects on anti-thrombosis and anti-inflammation partly by antioxidant action and partly by direct modulation of the respective processeds. In conclusion, the n-BuOH and $CH_2Cl_2$ fractions from leaves of Z, schinifolium can be utilized as the proper ingredients of functional foods for preventing chronic degenerative disease.

Effect of Taeeumjoweetang on the Body Composition, Serum Lipid Level and Antioxidant Enzyme Activity of Obese Female College Students (태음조위탕의 적용이 태음인 비만여대생의 신체조성, 혈청지질농도 및 혈중 항산화 효소에 미치는 효과)

  • Kim, Hye-Ju;Ahn, Hong-Seok;Oh, Eun-Ha;Kim, Young-Locke
    • Journal of Sasang Constitutional Medicine
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    • v.23 no.3
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    • pp.391-401
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    • 2011
  • 1. Objectives: Though the eating habits have improved and the living method has become convenient according to the economic growth thanks to the modern industrialization, because of the lack of exercise, obesity, wrong eating habits and stress etc, various symptoms of disease of adults are on the rise. This is the phenomenon that happens as the eating life has become life in the West along with the inundation of the western culture in our society. In this perspective, there has been many various clinical research that's been proceeded so far about the physical constitution and obesity, but there has been little research on the objective analysis of the clinical research about the alimentotherapy using taeeumjoweetang. 2. Methods: In this research we have checked the weights, fat rates, fat weight, abdominal fat rate, blood pressure, and BMI over the objects of the women that were diagnosed as lunisolar system as their physical constitution, and assessed the paramecium lipid, in-blood antioxidation enzyme and the damage of oxidization in the urine by physical constitution-specific of the body shapes that were determined by BMI. The statistical analysis of the current research was processed by using of SPSS 17.0 program. We have figure out statistical amounts such as the arithmetic average, average deviation rate and percentage number. Fro the verification of he significancy of each elements, we have used the paired t-test, ANOVA, Chi-square test at the level of p<0.05. 3. Results and Conclusions: Their characteristics are age $21.20{\pm}1.35$, height $160.30{\pm}6.11cm$, weight $64.66{\pm}8.72kg$, fat rates are $35.97{\pm}4.87%$, fat amount $23.40{\pm}5.48$, abdominal fat rate $0.823{\pm}0.03$, BMI $25.12{\pm}2.79kg/m^2$, and systolic blood pressure $111.60{\pm}10.28mmHg$ and diastolic blood pressure $68.60{\pm}7.43mmHg$ and we have let them take the medicine twice a day for 8 weeks. The clinical result for the Cholesterol, Triglyceride, HDL-cholesterol, LDL-cholesterol, SGOT, SGPT, of the object people was that for the function of the liver, the result of the SGOT and SGPT test was $17.16{\pm}3.05$, $15.00{\pm}2.99IU/L$, which was a decrease, and had statistical meaning, but for the SGOT, though the figure reduced to $11.92{\pm}4.61$, $10.80{\pm}3.07$, it had no statistical meaning. For the whole cholesterol level, the figure reduced to $169.00{\pm}19.95$, $160.08{\pm}22.52$ mg/dL and had statistical significance(p<0.05). Neuter fat number, Triglyceride has slightly increased to $67.52{\pm}36.32$, $68.08{\pm}47.33$ mg/dL but did not have any statistical meaning. The antioxdant enzyme marker standard marker, SOD has increased to $2.52{\pm}0.73$, $2.86{\pm}0.60U/ml$, and had statistical significance(p<0.01). Catalase also increased by $0.63{\pm}0.18$, $1.07{\pm}0.25mmol/ml$ and had statistical meaning(p<0.01). GPx also increased to $204.76{\pm}32.64$ nmol/ml and had statistical meaning(p<0.01). But, for the Total antioxidant, though it has raised to $1.51{\pm}0.26$, $1.57{\pm}0.17nmol/{\mu}l$, it did not have any statistical meaning. MDA of oxidative stress marker has decreased to $1.70{\pm}0.68{\mu}g/ml$, $1.21{\pm}0.50{\mu}g/m$ and had statistical significance(p<0.01). 8-OHdG also decreased $3.35{\pm}0.95ng/ml$, $2.21{\pm}0.50ng/ml$ and had statistical meaning(p<0.01). In this research, we have analyzed the various markers relating to BFM and changes in oxidative enzyme in blood by takingtaeeumjoweetang. Taeeumjoweetang has the positive effect on inbody antioxidant system and reducing the content of cholesterol, which is proven to help losing weight and improving hyperlipidemia statistically. With this research, we hope to improve the lifestyle of those who are either obese or need to manage their dietary habits, and also to become the touchstone of integrating Oriental Medicine with the science of food & nutrition.

Treatment Outcome of Postoperative Radiotherapy in Extrahepatic Bile Duct Cancer (간외담관암의 수술 후 방사선치료 성적)

  • Choi, Young-Min;Cho, Heung-Lae
    • Radiation Oncology Journal
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    • v.21 no.1
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    • pp.27-34
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    • 2003
  • Purpose : To evaluate the efficacy of radiotherapy, and the factors affecting survival in patients of extrahepatic bile duct cancer, by analyzing the results of postoperative radiotherapy Materials and Methods : Between October 1991 and July 2001, 21 patients with extrahepatic bile duct cancer, who received radiotherapy after a radical resection, were retrospectively reviewed. The patients' ages ranged from 39 to 75 years, with a median of 61 years, and a male to female ratio of 16 to 5. The numbers of patients with proximal and distal bile duct cancer were 14 and 7, respectively. From the postoperative pathological examination, 19 of the patients were found to have microscopic residues, and 7 to be lymph node positive. Patients with AJCC stages I, II and III were 10, 10 and 1, respectively. The total radiation dose administered was 4,500$\~$6,300 cGy, with a median dose of 5,040 cGy. The follow up period was 20$\~$81 months, with a median of 57.5 months. Results : The overall and disease free survival rates at 3 and 5 years were 41.0 and 29.3$\%$, and 41.6 and 29.7$\%$, respectively. The influences of age, sex, tumor location, differentiation, microscopic residue, neural invasion, 7 and N stage, the stage itself, the dose of radiation and chemotherapy, on survival were evaluated. The T stage and the stage itself were found to be significant from a univariate analysis (p<0.05), but the degree of significance was limited by the small number of patients. A recurrence occurred in 12 patients (57.1$\%$), 5 in locoregional sites, 4 in distant sites and 3 in a combination of locoregional and distant sites, and the sites of distant metastasis were the liver, 6, and the bone, 1 Grade 2 or 3 acute leucopenias occurred in 2 patients and grade 2 chronic peptic ulcers occurred in 4, who were all recovered by conservative management. Conclusion : Postoperative radiotherapy is feasigbls in extrah데atic bile duct cancer, with tolerable toxicity, but prospective studies, with a large patient enrollment, are needed for the evaluation of the effects of postoperative radiotherapy and the related prognostic factors.

Clinical Characteristics of Pneumococcal Bacteremia in Adults : The Effect of Penicillin Resistance on the Mortality of Patients with Pneumococcal Bacteremia (폐렴구균 균혈증에서 폐렴구균의 페니실린 내성 여부가 사망률에 미치는 영향)

  • HwangBo, Bin;Yoon, Ho-Il;Lee, Sang-Min;Choi, Seung-Ho;Park, Gye-Young;Yoo, Chul-Gyu;Lee, Choon-Taek;Kim, Young-Whan;Han, Sung-Koo;Min, Kyung-Up;Kim, You-Young;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.2
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    • pp.184-194
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    • 1999
  • Backgrounds : The advent of penicillin has led to the marked reduction in the mortality from pneumococcal bacteremia, however, the mortality is still relatively high in this post-antibiotic era. Actually the prevalence of infection due to penicillin-resistant penumococci is increasing worldwide, and it is especially high in Korea due to irrelevant use of antibiotics. So, the high mortality of pneumococcal sepsis might be related to the emergence of penicillin-resistant strains, however, many other antibiotics, which eradicate pneumococci effectively, are available in these days. This has led us to suspect the role of penicillin-resistance in the high mortality rate. In this study, we evaluated the effect of penicillin resistance on the mortality of patients with penumococcal bacte remia. Methods: The study population consisted of 50 adult patients with penumococcal bacteremia who were admitted between Jan, 1990 and July, 1997. Medical records were analyzed retrospectively. Results: Most of the patients (96%) had underlying diseases. The most common local disease associated with pneumococcal bacteremia was pneumonia (42%), which was followed by spontaneous bacterial peritonitis (14%), cholangitis (10%), meningitis (8%), liver abscess (4%), pharyngotonsillitis (4%), sinusitis (2%) and cellulitis (2%). While the overall case-fatality rate in this study was 24%, it was higher when peumococcal bacteremia was associated with pneumonia (42%) or meningitis (50%). The rate of penicillin resistance was 40%, which was increased rapidly from 1991. The rate of penicillin resistance was significantly higher in patients with the history of recent antibiotics use and hospitalization within 3 months respectively. The clinical manifestations, that is, age, severity of underlying diseases, nosocomial infection, associated local diseases, and the presence of shock or acute renal failure were not statistically different between the patients with penicillin-resistant and -sensitive pneumococcal bacteremia. The mortality of patients infected with penicillin-resistant pneumococci was not statistically different from those with penicillin-sensitive pneumococcal bacteremia. Conclusion: Penicillin resistance is not associated with high mortality in adult patients with pneumococcal bacteremia. As the overall mortality is high, active penumococcal vaccination is recommended in patients with high risk of infection.

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Beneficial Effects of Acanthopanax senticosus Extract in Type II Diabetes Animal Model via Down-Regulation of Advanced Glycated Hemoglobin and Glycosylation End Products (제2형 당뇨 동물모델에서 가시오가피 추출물의 당화혈색소 및 최종당화산물 억제를 통한 혈당조절 효과)

  • Kwon, Han Ol;Lee, Minhee;Kim, Yong Jae;Kim, Eun;Kim, Ok-Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.7
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    • pp.929-937
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    • 2016
  • The purpose of this study was to investigate the effect of Acanthopanax senticosus extract (ASE) (ethanol : DW=1:1, v/v) on inhibition of type 2 diabetes using an OLETF rat model via regulation of HbA1c and AGEs levels. Supplementation with ASE 0.1% and 0.5% effectively lowered levels of glucose, insulin, oral glucose tolerance test, and Homa-insulin resistance, suggesting reduced insulin resistance. Blood levels of HbA1c and AGEs were significantly reduced in a dose-dependent manner. As oxidative stress plays a key role in accelerating production of HbA1c and AGEs, which worsen symptoms of type 2 diabetes, levels of malonaldehyde and pro-inflammatory cytokines were measured. Lipid peroxidation in both blood and liver tissues was significantly reduced, and induction of pro-inflammatory cytokines interleukin-${\beta}$ and tumor necrosis factor-${\alpha}$, which elevate production of HbA1c and AGEs, was inhibited (P<0.05). To evaluate the possible cellular events after AGEs receptor activation, genetic expression of protein kinase C (PKC)-${\delta}$ and transforming growth factor (TGF)-${\beta}$ was measured by real-time polymerase chain reaction. Supplementation with both ASE 0.1% and 0.5% significantly inhibited mRNA expression of PKC-${\delta}$ and TGF-${\beta}$, indicating that ASE may have beneficial effects on preventing insulin-resistant cells or tissues from progressing to diabetic complications. Taken together, ASE has potential to improve type 2 diabetes by inhibiting insulin resistance and protein glycosylation, including production of HbA1c and AGEs. Anti-oxidative activities of ASE are a main requisite for reducing production of HbA1c and AGEs and are also related to regulation of the PKC signaling pathway, resulting in suppression of TGF-${\beta}$, which increases synthesis of collagen, prostaglandin, and disease-related proteins.

Clinical Characteristics of Pulmonary Histiocytosis X (폐조직구증식증의 임상적 특징)

  • Hwang, Yong-Ii;Park, Gun-Min;Yim, Jae-Joon;Yoo, Chul-Gyu;Lee, Choon-Taek;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.4
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    • pp.346-353
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    • 2001
  • Background : Pulmonary Langerhans cell histiocytosis forms part of a spectrum of diseases that are characterized by a monoclonal proliferation and infiltration of organs by Langerhans cells. Several organ systems may be involved in Langerhans cell histiocytosis, including the lungs, bone, skin, pituitary gland, liver, lymph nodes and thyroid. Pulmonary histiocytosis X represents 2.8% of interstitial lung disease. Here we present the clinical, radiological, therapeutic aspects of pulmonary histiocytosis X. Method : Fourteen cases of biopsy-proven pulmonary histiocytosis X patients who were diagnosed in Seoul National University Hospital during the period from January 1990 to December 1998 were analyzed retrospectively. Result : There were 12 men and 2 women in this study. The initial presenting symptoms were dyspnea, cough, chest pain, which was associated with the pneumothorax, and chest radiography abnormalities. Only 8 patients (57%) were smokers. There were 5 patients with extra-pulmonary histiocytosis (pituitary, bone, skin). Eight patients had received the chemotherapy. There were no mortalities and only one patient experienced an aggravation of symptom during the follow-up period. Conclusion : In contrast to previous reports from other countries, the patients with pulmonary histiocytosis X in this study presented with several different clinical characteristics, such as a male predominance, relatively low smoker's rate, and a better prognosis.

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Risk Factors of Non-alcoholic Steatohepatitis in Childhood Obesity (비만아에서 비알코올성 지방간염의 위험요인)

  • Yun, Eun-Sil;Park, Yong-Hun;Choi, Kwang-Hae
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.10 no.2
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    • pp.179-184
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    • 2007
  • Purpose: Obesity has recently emerged as a significant health problem in the pediatric population, and the prevalence of non-alcoholic fatty liver disease is increasing in tandem with a significant rise in childhood obesity. Therefore, this study was conducted to clarify the risk factors of non-alcoholic steatohepatitis in obese children. Methods: We enrolled 84 obese children who visited the pediatric obesity clinic at Yeung-Nam university hospital. The patients were divided into two groups based on their alanine aminotransferase (ALT) level (separated at 40 IU/L), and the mean of ages, total cholesterol levels, HDL-cholesterol levels, LDL-cholesterol levels, triglyceride (TG) levels, as well as the mean obesity index, and body fat percentage of the two groups were then compared. Results: When the mean of ages ($10.5{\pm}1.6$ vs. $10.7{\pm}2.0$ years), total cholesterol levels ($183.0{\pm}29.1$ vs. $183.7{\pm}31.3$ mg/dL), HDL-cholesterol levels ($53.0{\pm}10.2$ vs. $55.7{\pm}13.0$ mg/dL), LDL-cholesterol levels ($113.4{\pm}30.2$ vs. $113.0{\pm}30.0$ mg/dL), triglyceride levels ($99.4{\pm}62.9$ vs. $114.2{\pm}47.3$ mg/dL), obesity indexes ($44.7{\pm}12.2$ vs. $47.9{\pm}15.1%$), and body fat percentages ($32.7{\pm}5.0$ vs. $34.0{\pm}4.8%$) of group 1 (ALT${\leq}$40 IU/L) were compared with those of group 2 (ALT${\geq}$41 IU/L), no significant differences were observed (p>0.05). However, hypertriglyceridemia (TG${\geq}$110 mg/dL) was more frequent in group 2 than in group 1 (p=0.023). Conclusion: TG may be an important risk factor in non-alcoholic steatohepatitis and further study regarding the risk factors in non-alcoholic steatohepatitis is required.

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