• Biomolecules & Therapeutics
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• 제13권2호
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• pp.65-77
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• 2005

Present article reviews about clinical pharmacology of mycophenolic acid (MPA), the active form of mycophenolate mofetil (MMF), as widely used component of immunosuppressive regimens in the organ transplantation field. MMF, used alone or concomitantly with cyclosporine or tacrolimus, has approved in reducing the incidence of acute rejection and has gained widespread use in solid organ such as kidney, heart and liver transplantation. The application of MPA and development of MMF has shown a considerable impact on immunosuppressive therapy for organ transplantation as a new immunosuppressive agent with different mechanism of action from other drugs after early 1990s. In particular aspect, use of MMF, a morpholinoethyl ester of MPA, represented a significant advance in the prevention of organ allograft rejection as well as allograft and patient survival. In considering MMF clinical data, it is important to note that there is a strong correlation between high MPA area under curve(AUC) values and a low probability of acute allograft rejection. Individual trials have shown that MMF is generally well tolerated and revealed that MMF decreased the relative risk of developing chronic allograft rejection compared with azathioprine. Recent clinical investigations suggested that improved effectiveness and tolerability will results from the incorporation of MPA therapeutic drug monitoring into routine clinical practice, providing effective MMF dose individualization in renal and heart transplant patients. Therefore, MMF has a selective immunosuppressive effect with minimal toxicity and has shown to be more effective that other agents as next step of immunosuppressive agents and regimens that deliver effective graft protection and immunosuppression along with a more favorable side effect.

• Childhood Kidney Diseases
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• 제19권2호
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• pp.176-179
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• 2015

Rituximab (RTX), a monoclonal antibody against the B-cell marker CD20, is commonly used as a treatment for antibody-mediated diseases or B-lymphocyte-mediated diseases. Destruction of B cells may reverse the disease course in many conditions; however, patients who are treated with RTX cannot respond appropriately to de novo infection due to lack of B lymphocytes. Here, we report one such case. A 7-year-old renal allograft recipient presented with severe anemia due to parvovirus infection after RTX treatment. The patient had focal segmental glomerulosclerosis and had received cadaveric kidney transplantation 6 months previously. She was treated with high-dose steroid for acute rejection and RTX for Epstein Barr Virus infection 3 months previously. At presentation, her hemoglobin level was 5.4 g/dL and leukocyte and platelet counts were normal. She had microcytic normochromic anemia and high viral load of parvovirus B19(70,578 copies/mL). Intravenous immunoglobulin ($200mg/kg{\cdot}d$) treatment controlled the progression of anemia and parvovirus infection. De novo parvovirus infection during the B lymphocyte-depletion period may have precipitated the severe anemia in this case. Close monitoring of infection is required after RTX therapy.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제29권3호
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• pp.186-190
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• 2003

본과에서는 신장 이식자에서 매우 드물게 발현되는 구강내의 카포시 육종을 경험하였으며 이와 같이 장기 이식 후 면역 억제제를 투여하는 환자에서 구강내 카포시 육종의 발현시에는 전신적으로 이환된 경우가 많으므로 특별한 주의를 요하리라 사료된다.

• 한국임상약학회지
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• 제12권1호
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• pp.13-21
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• 2002

After the introduction of cyclosporin, the graft survival rate of renal transplant and patients' life expectancy have been greatly improved. However, cyclosporin is known to cause several undesirable side effects, one of which is hyperuricemia, which may subsequently cause gouty nephropathy and graft dysfunction. The purpose of this study was to evaluate the frequency and predisposing factors of hyperuricemia in cyclosporin-treated patients within one year of kidney transplantation and uricosuric efficacy of benzbromarone. The patients who were treated with cyclosporin after kidney transplantation in 1998 and the patients who were treated with benzbromarone for the control of cyclosporin-induced hyperuricemia in 1999 were investigated retrospectively. Among the 76 patients in cyclosporin-treated patients in 1998, hyperuricemia occurred in 55 patients $(72.4\%)$ and the mean time from kidney transplantation to occurrence of hyperuicemia was $5.0\pm8.0$ months. In 1999, 22 patients were treated with benzbromarone for hyperuricemia and their mean time from kidney transplantation to occurrence of hyperuricemia was $4.5\pm10.4$ months. Acute rejection developed in one patient $(4.8\%)$ out of 21 normo-uricemic patients and 11 patients $(20.0\%)$ out of 55 hyperuricemic patients in 1998. The difference of rejection rate in these two groups was significant (p<0.001). There was no difference of rejection rate between before and after treatment of benzbromarone. Cyclosporin trough levels did not show a significant correlation with the serum uric acid levels among the three groups. However, hyperuricemic patients showed significantly higher serum creatinine levels than patients with normal uric acid levels (p<0.001). Benzbromarone decreased serum uric acid levels from $8.3\pm2.3\;mg/dl\;to\;5.1\pm2.0\;mg/dl$ (p<0.0001) and normalizing serum uric acid in all of 22 patients. Except for one patient $(4.5\%)$ who experienced diarrhea, no significant side effect was noted.

• 대한이식학회지
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• 제32권4호
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• pp.104-107
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• 2018

Mucormycosis is an extremely rare but potentially life-threatening fungal infection. Gastrointestinal (GI) mucormycosis is very rare and occurs primarily in highly malnourished patients, especially in infants and children. A 55-year-old man with end-stage renal disease due to diabetic nephropathy, who had undergone deceased donor kidney transplantation 2 years prior, complained of abdominal pain and distension with a 3-day duration. Computed tomography revealed diffuse gastric wall thickening, and a huge amount of grey colored necrotic debris surrounded by erythematous erosive mucosa was observed at the antrum to upper body by GI endoscopy. The microscopic examination obtained from a GI endoscopic specimen demonstrated peptic detritus with numerous non-septate mucor hyphae in the mucosa and submucosa. Mucormycosis was diagnosed based on the clinical findings and morphological features. A total gastrectomy was performed and an antifungal agent was administered. A microscopic examination of the surgical specimen demonstrated invasive mucormycosis with numerous fungal hyphae with invasion into the mucosa to subserosa. The patient and graft were treated successfully by total gastrectomy and antifungal therapy.

• 기본간호학회지
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• 제6권1호
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• pp.78-95
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• 1999

The grafting of a kidney has been found to be the best medical treatment for patients who have renal insufficiency failure, but the patients still have experienced much trouble and apprehension. This study was done to further nursing theory developing for patients who have has a kidney graft from another person. The research method followed grounded theory methodology of Strauss and Corbin. The subjects were three female and four male patients. This study done befween Oct. 1997 and Mar. 1998. All of the subjects were interviewed by the author. Interview were done by the long interview technique and observation. In the process of data analysis, 'heart-boiling' was found to be the core phenomenon. The results were composed to 101 concepts. These concepts were grouped into nineteen categories, and then to twelve categories. There were 12 super-class categories as follows ; 'pain', 'heart-boiling', 'experience of dialysis', 'term of admission to a hospital', 'support of other person', 'dependence on God', 'direction', 'negative reaction', 'positive reaction', 'comfortable', 'lacking', 'acceptance'. In this process, 14 hypotheses were derived from the categories as follows ; (1) The more experience with dialysis that the patients have, the stronger the heart-boiling will tend to be. (2) The less experience with dialysis the patients have, the weaker the heart-boiling will tend to be. (3) The longer admission to hospital the patients have, the stronger the heart-boiling will be. (4) The shorter the admission to hospital the patients have, the weaker the heart-boiling will be. (5) The weaker the intense-grief is, the more positive the reaction to heart-boiling the patients wll have. (6) The stronger the intense-grief is, the more negative the reaction to heart-boiling the patients will have. (7) The stronger the support of other persons that the patients have, the more positive the reaction to heart-boiling the patients will have. (8) The weaker the support of other person that the patients have, the more negative the reaction to heart-boiling the patients will have. (9) The stronger the dependence on God that the patients have, the mure positive reaction to heart-boiling the patients will have. (10) The weaker the dependence on God that the patients have, the more negative reaction to heart-boiling the patients will have. (11) The more positive thoughts that the patients have, the more positive reaction to heart-boiling the patinets will have. (12) The more negative thoughts that the patients have, the more negative reaction to heart-boiling the patients will have. (13) The more positive reaction the patients have, the more free from heart-boiling the patients tend to be. (14) The more negative reaction the patients have, the less free from heart-boiling the patients tend to be. From the analysis of observed data and comparing each class, I concluded that there are four formula relation types between reaction of patients and heart-boiling. (1) If patients have the experience of dialysis, have a long term admission to hospital, are strong in heart-boiling, depend on God, have positive thoughts and another's strong support, they experience release by positive reaction to the intense-grief. (2) If patients have the experience of dialysis, have a short term admission to hospital, are weak in heart-boiling, do not depend on God, have negative thoughts, and have few supports from others, they experience attachment to heart-boiling though a negative reaction. (3) If patients have the experience of dialysis, have a long term admission to hospital, are strong in heart-boiling, do not depend on God, and have negative thoughts, they experience attachment to heart-boiling through negative reaction in spite of support from another. (4) If patients have the experience of dialysis, have a long term admission into hospital, are strong in heart-boiling and satisfaction is low, but they have positive thoughts, then they experience acceptance and harmony through the positive reaction to heart-boiling. The results of this study are expected to help the way nurses care for patients who have had a kidney graft from another.

• Tuberculosis and Respiratory Diseases
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• 제45권6호
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• pp.1199-1213
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• 1998

연구배경 : 최근 면역기능저하 환자들이 급증하고 있으며 이들에 있어서 새로 발생된 설명이 불가능한 폐침윤은 매우 흔하면서도 환자의 생명을 위협할 수 있는 상황으로 발전할 수 있다. 폐진균증은 이런 임상상에서 폐침윤의 중요한 원인으로 대두되고 있으나 이에 대한 연구가 많지 않아 본 연구를 시행하였다. 방 법 : 1996년 10월부터 1998년 4월까지 삼성서울병원에서 면역기능저하 환자 중 새로운 폐침윤이 있었던 환자로 조직학적으로 폐에서 진균이 증명되었거나 정상적으로 균이 자리지 않는 부위(sterile)에서 시행한 배양검사장 진균이 배양된 환자들을 대상으로 임상적 특정, 방사선학적 소견, 진단적 검사, 치료 및 그 결과에 대해 후향적인 조사를 시행하였다. 결 과 : 총 13명의 환자 (M : F=8 : 5, 연령 중앙값 47세)에서 14예의 폐진균증이 진단되었다. 진단은 asperogillosis가 12예였고 mucormycosis가 2예였다. 혈액암 환자 9명에서 10예, 장기이식 환자에서 4예의 폐진균증이 진단되었다. 3예에서는 진단당시 경험적 amphotericin B를 중앙값 9일(8-21일)간 투여받고 있었다. 혈액암군 10예 중 9예에서 폐침윤 발견당시 백혈구 감소증이 중앙값 16일동안 지속되었으며 발열(9/10), 기침(6/10), 가래(5/10), 호흡곤란(4/10), 흉통 (5/10), 악설음(4/10) 등의 증상과 징후가 흔하게 관찰되었다. 반면에 장기이식환자군에서는 증상 및 징후가 뚜렸하지 않은 경우가 많았다(p<0.05). 단순 흉부촬영상으로 새로운 폐침윤은 단일 혹은 다발성의 결절(6/14)이나 경결(consolidation)(8/14)의 형태로 나타났으며 흉부 단층촬영상에서는 간유리음영(14/14), 흉수(5/14), 동공형성(7/14) 등의 소견이 관찰되었다. 확진한 방법으로는 개흉술이 10예, 비디오 흉강경술이 2예, 경피적침흡인술이 1예, 농양의 농 배양검사가 1예였다. 모든 환자는 amphotericin B(591-2806mg) 투여를 받았으며 1예에서 liposomal amphotericin B, 1예에서 경구 itraconazole로 치료를 부분적으로 시행하였다. Amphotericin B 투여 후 12/14예에서 폐병변의 호전이 관찰되었으며 14예중 4예에서 사망하거나 회복이 불가능한 상태로 퇴원하였다. 결 론 : 혈액암의 치료로 과립구감소증이 있는 환자나 장기이식 환자에서 새로운 폐침윤이 결절이나 경결의 형태로 발현하면, 증상이 미미하거나 경험적 amphotericin B를 투여하고 있더라도 폐진균증을 의심을 해야하며 적극적인 진단과 치료로써 예후를 호전시킬 수 있을 것으로 기대된다.

• International Journal of Oral Biology
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• 제33권4호
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• pp.205-211
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• 2008

Gingival overgrowth can cause dental occlusion and seriously interfere with mastication, speech, and dental hygiene. It is observed in 25 to 81% of renal transplant patients treated with cyclosporine A (CsA). CsA-induced gingival overgrowth (CIGO) is caused by quantitative alteration of the extracellular matrix components, particularly collagen. However, the molecular mechanisms involved in the pathogenesis of CIGO remain poorly understood, despite intense clinical and laboratory investigations. The aim of the present work is to identify differentially expressed genes closely associated with CIGO. Human gingival fibroblasts were isolated by primary explant culture of gingival tissues from five healthy subjects (HGFs) and two patients with the CIGO (CIGO-HGFs). The proliferative activity of CsA-treated HGFs and CIGO-HGFs was examined using the MTT assay. The identification of differentially expressed genes in CsA-treated CIGO-HGF was performed by differential display reverse transcriptase-polymerase chain reaction (RT-PCR) followed by DNA sequencing. CsA significantly increased the proliferation of two HGFs and two CIGO-HGFs, whereas three HGFs were not affected. Seven genes, including the beta subunit of prolyl 4-hydroxylase (P4HB) and testican 1, were upregulated by CsA in a highly proliferative CIGO-HGF. The increased P4HB and testican-1 mRNA levels were confirmed in CsA-treated CIGO-HGFs by semiquantitative RT-PCR. Furthermore, CsA increased type I collagen mRNA levels and suppressed MMP-2 mRNA levels, which are regulated by P4HB and testican-1, respectively. These results suggest that CsA may induce gingival overgrowth through the upregulation of P4HB and testican-1, resulting in the accumulation of extracellular matrix components.

• Tuberculosis and Respiratory Diseases
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• 제55권4호
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• pp.395-401
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• 2003

말기 신부전으로 3개월 선에 신장 이식술을 시행받고 면역억제제를 복용 중이던 54세 여자 환자가 기침과 발열을 주소로 내원하였다. 지역사회 획득성 폐렴을 의심하여 levofloxacin과 amikacin을 투여한 후 환자의 증상과 방사선학적 소견이 호선되어 퇴원하였고 이후 2개월이 지나 다시 증상이 재발하여 재입원하였다. 객담 항산균 도말검사 및 결핵균 PCR이 음성이었으나 기관지 세척액에 대한 결핵균 PCR이 양성으로 나와 결책을 진단한 후 항결핵제 치료를 시작하였고 이후 객담 및 기관지 세척액에 대한 항산균 배양 검사 상 모두에서 결핵균이 자랐고 치료 후 환자의 증상과 방사선학적 소견을 모두 호전시킬 수 있었다.

• Journal of Gastric Cancer
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• 제21권2호
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• pp.191-202
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• 2021

Purpose: A near-infrared (NIR) fluorescence imaging is a promising tool for cancer-specific image guided surgery. Human epidermal receptor 2 (HER2) is one of the candidate markers for gastric cancer. In this study, we aimed to synthesize HER2-specific NIR fluorescence probes and evaluate their applicability in cancer-specific image-guided surgeries using an animal model. Materials and Methods: An NIR dye emitting light at 800 nm (IRDye800CW; Li-COR) was conjugated to trastuzumab and an HER2-specific affibody using a click mechanism. HER2 affinity was assessed using surface plasmon resonance. Gastric cancer cell lines (NCI-N87 and SNU-601) were subcutaneously implanted into female BALB/c nu (6-8 weeks old) mice. After intravenous injection of the probes, biodistribution and fluorescence signal intensity were measured using Lumina II (Perkin Elmer) and a laparoscopic NIR camera (InTheSmart). Results: Trastuzumab-IRDye800CW exhibited high affinity for HER2 (K_D=2.093(3) pM). Fluorescence signals in the liver and spleen were the highest at 24 hours post injection, while the signal in HER2-positive tumor cells increased until 72 hours, as assessed using the Lumina II system. The signal corresponding to the tumor was visually identified and clearly differentiated from the liver after 72 hours using a laparoscopic NIR camera. Affibody-IRDye800CW also exhibited high affinity for HER2 (K_D=4.71 nM); however, the signal was not identified in the tumor, probably owing to rapid renal clearance. Conclusions: Trastuzumab-IRDye800CW may be used as a potential NIR probe that can be injected 2-3 days before surgery to obtain high HER2-specific signal and contrast. Affibody-based NIR probes may require modifications to enhance mobilization to the tumor site.