• 대한바이러스학회지
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• 제26권1호
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• pp.47-58
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• 1996

Histopathological vascular changes in hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus include increased vascular permeability, disseminated intravascular coagulation, thrombocytopenia and changes in coagulation activity. Although vascular endothelial cells of main target organs such as kidney infected with Hantaan virus are not damaged but swelling of endothelial cells, perivascular exudates and infiltration of mononuclear cells and fresh interstitial hemorrhages are common. However, the pathogenesis of cell infiltration and hemorrhages around vascular endothelial cells are not well understood. Some endothelial cell molecules or vascular adhesins that acts as adhesion moleulces for leukocyte are expressed on endothelial cells close to site of inflammation. However, whether the expression of endothelial adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule (ICAM-1) and endothelial leukocyte adhesion molecule (ELAM) on vascular endothelial cells are increased by infection with Hantaan virus has not been studied. In this study, the relationship between the expression of VCAM-1, ICAM-1 and ELAM and adhesion of mononuclear cells on endothelial cells of human blood vessels infected with Hantaan virus was investigated. The endothelial cells of umbilical vein was passaged three times in culture medium and the monolayered cells were infected with $10^5\;pfu/ml$ of Hantaan virus grown in Vera E6 cell cultures. The multiplication of virus in cultured endothelial cells was monitored by immunohistochemistry and the expression of adhesion molecules was demonstrated by immunohistochemistry using monoclonal antibodies against VCAM-1, ICAM-1 and ELAM. And in situ hybriditation against ICAM-1 was also performed. The endothelial adhesion molecules, VCAM and ICAM, were expressed after 6 hours postinfection, respectively, and their expressions lasted for 72 hours. Similar expression of VCAM and ICAM appeared on endothelial cells by infection with virus, but the expression of ELAM was not recognized up to 72 hours postinfection. Microscopically, it was noted that many monocuclear cells adhered on endothelial cells infected with viruses. In an electronmicroscopic study, the transendothelial migration of mononuclear cells was observed on monolayered endothelial cells infected with virus. This results suggested that the endothelial adhesion molecules, particulary VCAM and ICAM, might be expressed on endothelial cells by infection with Hantaan virus and these molecules play a key role in the adhesion and extravasation of inflammatory cells around blood vessels.

• Pediatric Infection and Vaccine
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• 제21권2호
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• pp.104-113
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• 2014

목적: 본 연구는 최근 10년 동안 전주 예수병원에 쯔쯔가무시병으로 입원한 환자를 조사하여 소아와 성인의 임상 양상을 비교하고자 하였다. 방법: 2003년 1월부터 2012년 12월까지, 쯔쯔가무시병의 진단 기준에 포함되는 768명의 환자를 후향적으로 검토하여, 소아 49명, 성인 719명의 임상적 특징과 검사소견 및 합병증 등을 분석 비교하였다. 결과: 연도별 환자의 증가 추세는 소아와 성인 모두에서 뚜렷하게 보이지 않았고, 10월과 11월에 환자가 가장 많이 발생하였다. 남녀비에서 소아는 남아가 많은 반면에, 성인은 여자가 많았고, 거주 지역은 소아가 성인에 비해 도시가 더 많았다. 증상은 소아에서 발진과 가피가 많았고, 근육통은 성인에서 더 많았다. 검사상 소아는 빈혈이 많은 반면에, 혈소판, 간기능, 신기능의 이상 소견이 적었다. 입원 기간과 합병증에서는 성인보다 양호한 결과를 보였다. 소아에서 독시사이클린과 마크로라이드계열 항생제의 치료 효과를 비교하였을 때, 두 약제 간에 유의한 차이는 보이지 않았다. 결론: 쯔쯔가무시병 환자에서 소아는 남아에서 많았고, 발진 및 가피의 발생이 더 많았다. 검사상 이상 소견은 성인에 비해 경하였으며, 입원 기간이 짧고, 합병증이 적으며, 마크로라이드계열 항생제에도 동일한 치료 효과를 보였다. 따라서 유행 시기에, 소아에서 쯔쯔가무시병이 의심될 때에는, 세밀한 이학적 진찰과 혈청학적 검사를 실시하여 빠른 진단을 내릴 수 있도록 노력해야 하며, 상대적으로 부작용이 적은 마크로라이드계 항생제로도 좋은 치료 결과를 기대해 볼 수 있다.

• Pediatric Infection and Vaccine
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• 제26권3호
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• pp.199-205
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• 2019

엔테로바이러스 감염은 신생아에게 흔히 일어나며, 경한 감염에서부터 다기관 부전이나 사망에까지 이를 수 있다. 특히, 출생 시 모체로부터 수직 감염된 신생아들의 경우 심각한 질환에 이르게 될 수 있다. 본 증례의 환아는 모체에게서 엔테로바이러스의 수직 감염이 일어났으며, 파종 혈관내 응고장애, 간염, 그리고 심근염으로 빠르게 진행하였다. 환아가 태어난 시기가 엔테로바이러스의 유병률이 높은 6월인 점, 환아의 어머니와 형제에게서 고열이 있었던 점, 임상 증상 등을 고려하여 저자들은 환아가 엔테로바이러스의 수직 감염 가능성이 있다고 보고 검사와 치료를 진행하였다. 이 환아는 빈맥을 동반한 다양한 형태의 부정맥을 보였으며, 일반적인 치료에 반응을 잘 하지 않았으나, 엔테로바이러스 감염을 조기에 의심하고 치료하여 완전히 회복할 수 있었다. 신생아의 엔테로바이러스 감염에서, 응고장애를 동반한 간염과 심근염이 동시에 오는 경우는 드물다. 본 증례에서, 저자들은 응고장애를 동반한 간염과 다양한 형태의 부정맥을 동반한 엔테로바이러스 수직 감염을 조기에 진단하고 성공적으로 치료하였기에 보고하는 바이다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.215-217
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• 2016

Background: Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in Europe and North America, and it mainly affects older individuals. Many approaches are implemented in the management of CLL from a watch and wait (W&W) strategy to chemotherapeutic regimens. We here reviewed our clinical practice for the relevance of the W&W strategy in Lebanese CLL patients. Materials and Methods: A total of 95 patients with CLL diagnosed in four institutions in Lebanon, between 1992 and 2013, were selected and their files were reviewed. Characteristics of these patients were noted including age, sex, RAI and Binet scores, CBC values, presence of hepatomegaly or splenomegaly, performance of bone marrow biopsy or peripheral blood flux cytometry for diagnosis, adoption of W&W strategy, different chemotherapeutic regimens and the indications for treatment. Results: Some 38 patients (40%) diagnosed with CLL were women and 57 (60%) were men with a mean age of 65.1 years [36-89]. Of the total, 50.5%, 17.2%, 14%, 7.5% and 10.8% had an RAI score at diagnosis of 0, 1, 2, 3 and 4, respectively, while 65.6%, 17.2% and 17.2% had Binet scores of I, II and III. The mean lymphocyte count at diagnosis was $39885/mm^3$ [1596-290000], the mean hemoglobin level was 12.7 g/dl [6.2-17] and the mean platelet count was $191255/mm^3$ [14000-458000]. While 26.3% of patients with CLL had splenomegaly, only 7.4% had hepatomegaly. Some 33.7% had undergone a bone marrow biopsy, 66.3% flow cytometry of circulating blood and 5.3% a lymph node biopsy. Overall, the W&W was adopted in 62.4% (58) of patients with a mean duration of 37.7 months [3-216]. The W&W was used in 82.6%, 73.3%, 46.2%, 14.3% and 0% of patients having RAI scores of 0, 1, 2, 3 and 4, respectively, and, it was used in 80%, 46.7% and 6.25% with Binet scores of I, II and III. The most frequent indication for treatment was anemia and thrombocytopenia, accounting for 32.7% of cases. The most frequently used chemotherapeutical regimens were chlorambucil until the end of the last century and flufarabine-cyclophosphamide-rituximab during the last decade. Conclusions: This retrospective review of CLL clinical practice showed an important implementation of the W&W strategy with a long duration, especially in early stage cases with low RAI or Binet scores.

• 대한의생명과학회지
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• 제3권2호
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• pp.83-88
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• 1997

범발성 혈관내 응고증은 패혈증 환자들에 있어 빈번히 발생하며 여러 가지 위급한 질병 상태에 관계하는 병리학적 상황이다. 범발성 혈관내 응고증은 기존의 복잡한 임상 상황을 더욱 어렵게 만들어서 높은 사망률의 원인이 된다. 그럼에도 불구하고 그것의 병인적 기전들은 완전히 규명되지 않았다. 본 연구는 범발성 혈관내 응고증의 발생에 관여하는 병인적 기전들의 이해를 위해 전향적으로 계획되었다. 15마리의 쥐를 대상으로 해서 연구목적에 따라 세 군으로 나누었다：I 군은 대조군으로서 내독소를 투여하지 않은 쥐들이고 (n=5), II 군은 내독소 투여 후 12시간이 경과한 쥐들이며 (n=5), III군은 내독소 투여 후 24시간이 경과한 쥐들이었다 (n=5). 실험적 범발성 혈관내 응고증은 일정량의 내 독소를 한번에 투여하여 유도하였다 (1mg/kg, E. coli serotype 055:B5). 실험대상 쥐들의 심장으로부터 직접 채혈하여 혈소판수, 섬유소원 농도, plasminogen 농도, 항트롬빈 III 농도, D-dimer, 보체성분 (C3 및 C4)을 측정하였다. 내독소를 투여한 II 군과 III 군에 있어 혈소판수, 섬유소원 (III 군의 경우는 오히려 증가), plasminogen, 항트롬빈 III, 그리고 C3등의 혈중 농도들이 대체로 감소하였고 D-dimer 농도는 증가함으로써 명백한 범발성 혈관내 응고증이 관찰되었다. 본 연구 결과들은 내독소에 의해 응고계, 섬유소용해계, 그리고 보체계와 같은 여러경로의 활성화가 유도될 수 있으며, 이로해서 범발성 혈관내 응고증 및 이차적인 중복 장기기능 부전이 발생하리라는 점을 시사하고 있다. 결국, 이와같은 실험적인 내독소 유도 범발성 혈관내 응고증에 있어 응고계 및 섬유소 용해계의 활성을 일으키는 다양한 기전에 관한 축척된 지식들은 그와 같은 질병의 예방 혹은 치료방법을 제공해 줄 것이다.

• Neonatal Medicine
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• 제18권1호
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• pp.14-22
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• 2011

신생아 출혈은 신생아실에서 흔하게 경험하는 증상 중 하나이며 신생아중환자실에서는 특히 미숙아에게 종종 발생하므로 신속한 진단 및 즉각적인 치료가 필수적이다. 신생아 출혈은 이환율과 사망률의 중요한 원인이 되며 심한 경우 생명을 위협할 수 있다. 특히 최근 들어 비약적인 신생아학의 발달로 인해 초극소저체중출생아를 포함한 미숙아들의 생존율이 높아지고 있어 혈액응고질환의 진단 및 치료의 중요성은 날로 높아져 간다고 하겠다. 출혈이 의심되는 신생아의 정확한 진단을 위해서는 출혈의 가족력, 산모의 병력, 과거 임신력, 신생아 및 산모의 약물복용여부를 포함한 자세한 병력청취가 무엇보다 주의 깊게 시행되어야 하고 특정부위에 국한되어 증상을 보이는지 아니면 광범위한 출혈인지 감별을 해야 한다. 혈소판감소증만 단독으로 보이는 신생아의 경우 자반증(petechiae)과 반상출혈(ecchymoses), 점막출혈 등이 동반될 수 있으나 대부분은 건강해 보이며 비타민 K 결핍출혈, 혈우병 같은 선천성 응고장애를 의심해 볼 수 있으며, 아파 보이는 신생아에서 폐, 위장관, 비뇨생식기계, 천자부위 등에서 출혈이 일어나는 경우는 파종성 혈관내응고증후군을 포함한 후천성 응고이상을 의심해 볼 수 있다. 특별히 외상의 흔적이나 난산의 병력이 없는 만삭아나 준미숙아 등에서 두개 내 출혈이 보이는 경우에도 반드시 혈액응고이상 질환을 의심해봐야 한다. 저자는 본 종설을 통해 신생아출혈을 유발하는 혈액응고질환에 대해 임상유형 및 발생기전에 따라 대해 1차성 및 2차성 응고이상질환으로 나누어 알아보고 이를 다시 선천성 응고장애질환과 후천성 응고장애질환으로 나눠 각각에 대해 최신지견을 토대로 자세히 살펴보고자 한다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.985-989
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• 2015

Background: Docetaxel, cisplatin, 5-fluorouracil (DCF) given every three weeks is an effective, but palliative regimen and significantly toxic especially in patients who have a low performance score. Here, we aimed to evaluate the efficacy and tolerability of a weekly formulation of DCF in locally advanced and metastatic gastric cancer patients. Materials and Methods: 64 gastric cancer patients (13 locally advanced and 51 metastatic) whose ECOG (Eastern Cooperative Oncology Group) performance status (PS) was 1-2 and who were treated with at least two cycles of weekly DCF protocol as first-line treatment were included retrospectively. The weekly DCF protocol included $25mg/m^2$ docetaxel, $25mg/m^2$ cisplatin, and 24 hours infusion of $750mg/m^2$ 5-fluorouracil, repeated every week. Disease and patient characteristics, prognostic factors, treatment response, grade 3-4 toxicity related to treatment, progression free survival (PFS) and overall survival (OS) were evaluated. Results: Of the patients, 41 were male and 23 were female; the median age was 63 (29-82) years. Forty-one patients were ECOG-1 and 23 were ECOG-2. Of the total, 81.2% received at least three cycles of chemotherapy. Partial response was observed in 28.1% and stabilization in 29.7%. Overall, the disease was controlled in 57.8% whereas progression was noted in 42.2%. The median time to progression was 4 months (95%CI, 2.8-5.2 months) and median overall survival was 12 months (95%CI, 9.2-14.8 months). The evaluation of patients for grade 3-4 toxicity revealed that 10.9% had anemia, 7.8% had thrombocytopenia and 10.9% had neutropenia. Non-hematologic toxicity included renal toxicity (7.8%) and thrombosis (1.6%). Conclusions: In patients with locally advanced or metastatic gastric cancer who were not candidates for DCF administered every-3-weeks, a weekly formulation of DCF demonstrated modest activity with minimal hematologic toxicity, suggesting that weekly DCF is a reasonable treatment option for such patients.

• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.5119-5124
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• 2012

Purpose: The aim of this retrospective study was to determine response rates, progression-free survival (PFS), overall survival (OS) and toxicity of gemcitabine and paclitaxel combinations with advanced or metastatic non-small cell lung cancer patients (NSCLC) who have progressive disease after platinum-based first-line chemotherapy. Methods: We retrospectively evaluated the file records of patients treated with gemcitabine plus paclitaxel in advanced or metastatic NSCLC cases in a second-line setting. The chemotherapy schedule was as follows: gemcitabine $1500mg/m^2$ and paclitaxel 150 mg/m2 administered every two weeks. Results: Forty-eight patients (45 male, 3 female) were evaluated; stage IIIB/IV 6/42; PS0, 8.3%, PS1, 72.9%, PS2, 18.8%; median age, 56 years old (range 38-76). Six (12.5%) patients showed a partial response (PR), 13 (27.1%) stable disease (SD), and 27 (56.3%) progressive disease (PD). The median OS was 6.63 months (95% CI 4.0-9.2); the median PFS was 2.7 months (95% CI 1.8-3.6). Grade 3 and 4 hematologic toxicities, including neutropenia (n=4, 8.4%), and anemia (n=3, 6.3%) were encountered, but no grade 3 or 4 thrombocytopenia. One patient developed febrile neutropenia. There were no interruption for reasons of toxicity and no exitus related to therapy. Conclusion: The combination of two-weekly gemcitabine plus paclitaxel was an effective and well-tolerated second-line chemotherapy regimen for advanced or metastatic NSCLC patients previously treated with platinum-containing chemotherapy. Although the most common and dose limiting toxicities were neutropenia and neuropathy, this regimen was tolerated well by the patients.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.637-642
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• 2014

The pathogenesis of hepatocellular carcinoma (HCC) related to habitual betel quid (BQ) chewing is unclear. Risk of HCCis increased with adverse hepatic fibrosis. This study aimed to assess the impact of chronic viral hepatitis on adverse hepatic fibrosis in HCC related to BQ chewing. This hospital-based case-control study enrolled 200 pairs of age- and gender-matched patients with HCC and unrelated healthy controls. Serologic hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV), ${\alpha}$-fetoprotein (AFP), and surrogate markers for significant hepatic fibrosis were measured. Information on substance-use habits was obtained with a questionnaire. By analysis of surrogate markers for hepatic fibrosis, the prevalence of significant hepatic fibrosis in patients chewing BQ was between 45.8% and 91.7%, whereas that for patients without BQ chewing was between 18.4% and 57.9%. The difference was significant (P <0.05 for each surrogate marker). Multivariate analysis indicated that cirrhosis with Child-Pugh C (odds ratio (OR) = 3.28; 95% confidence interval (CI), 1.29-8.37), thrombocytopenia (OR = 3.92, 95% CI, 1.77-8.68), AFP >400 mg/L (OR = 2.21, 95% CI, 1.05-4.66) and male gender (OR = 4.06, 95% CI, 1.29-12.77) were independent factors associated with habitual BQ chewing. In conclusion, adverse hepatic fibrosis and severe liver damage play important roles in the pathogenesis of BQ-related HCC, which could be aggravated by chronic hepatitis B and hepatitis C. BQ-cessation programs and prevention of chronic HBV/HCV infection are needed to prevent HCC related to BQ chewing.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.2703-2706
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• 2013

Purpose: This study was to determine the efficacy and safety of pemetrexed based chemotherapy in treating patients with metastatic gastric cancer who failed to respond to first and (or) second line chemotherapy. Patients and Methods: Metastatic gastric cancer patients who failed first and (or) second line chemotherapy, were enrolled. All patients were recruited from Jiangsu Cancer Hospital & Research Institute, and were treated with pemetrexed $500mg/m2$ (intravenous; on day 1), and a platinum (or irinotecan) every 3 weeks until disease progression, or intolerable toxicity. Evaluation on efficacy was conducted after two cycles of chemotherapy using the Response Evaluation Criteria for Solid Tumors. Toxicity was recorded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Results: From Jun 2011 to May 2013, 23 patients were enrolled. All eligible 23 patients completed at least 2 cycles of chemotherapy with pemetrexed based chemotherapy, and were evaluable. Their median age was 55 years (range 40 to 78 years). Seventeen patients were male and 6 female. Three patients (13%) achieved partial response, five patients (22%) stable, 15 patients (65%) with disease progression, and none with complete response. Grade 2 neutrophil suppression occurred in 4.3%, grade 3 in 13% of patients, and no grade 4 was reported. Thrombocytopenia was encountered as follows: 4.3% grade 2, 4.3% grade 3 and 4.3% grade 4. Incidence of anemia was 34.8% in grade 2, 8.7% grade 3 and 0% grade 4. Only 4.3% of patients required packed red blood cell infusion. Elevated transaminase were 4.3% in grade 2 and 0% in grade 3 or 4. Other toxicity included oral mucositis. Conclusions: Pemetrexed based chemotherapy is mildly effective in treating patients with metastatic gastric cancer with tolerable toxicity.