• Korean Journal of Clinical Pharmacy
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• v.9 no.2
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• pp.81-87
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• 1999

췌장이식의 성공률은 지난 10년 동안 상당히 상승되었다. International Pancreas Transplant Registry에 따르면 1995년 이래 미국에서만 매년 1,000건 이상의 췌장이식이 실시되고 있다. 장기이식후 나타나는 급성 거부반응은 이식 후 6개월 이내에 가장 높은 빈도수로 나타난다. 췌장이식환자에서는 신장을 이식한 것보다 두배나 높은 거부반응을 나타나며 이로 인한 입원율의 증가 항림프제(antilyinphocyte) 사용과 감염의 증가로 이환율이 높다. 더구나 Cyclosporine (CsA)을 기초로 한 면역억제제요법의 사용은 높은 급성 거부반응률(acute graft rejection)을 초래하여 이식한 장기의 조직손실이 문제가 되고 있다. 새로운 면역억제제인 Tacrolimus (FK506)의 사용은 이식환자에서의 거부반응을 감소시켜 생존율을 증가시키는 것으로 알려져 있다. Tacrolimus는 neutral macrolide로 cyclic peptide인 CsA과는 화학 구조는 매우 다르나 비슷한 면역억제 효과를 보인다. 하지만 Tacrolimus의 사용시 신경독성, 신독성, 특히 고혈당증의 발생률이 높아 일부 이식센터에서는 장기 이식 후에 사용하기를 꺼리기도 한다. 하지만 여러 연구논문에서 간과 신장 이식 후 급성 거부반응 예방에 Tacrolimus는 CsA에 비해 이점이 있는 결과를 발표하였다. 결과적으로, 현재 췌장이식 후 Tacrolimus를 기초로 한 면역억제의 효과에 대한 연구가 활발히 진행중이다. 따라서 본 연구에서는 1994-1996년 사이에 Tacrolimus 또는 CsA를 기초로 한 면역억제요법을 투여 받은 췌장이식환자 101명을 후향적으로 조사하여 Tacrolimus (n=54)와 CsA(n=57)의 급성 거부반응 예방 효과와 신부전 발생률을 비교하였다. 모든 환자는 항림프구 약물, Azathioprine, Prednisone을 이식 후 면역억제제로 투여 받았다 기준선으로부터 $20\%$ 이상의 혈청 creatinine의 상승이 있는 환자에서는 급성 신부전으로 정의하였고 신장생검법으로 거부반응을 진단하였다 Matched-pair analysis에 따르면 췌장이식환자의 6개월 생존율은 CsA군에서 $97\%$, Tacrolimus군에서 $96\%$로 별다른 차이가 없었으며 (p=0.57), 6개월간의 이식한 췌장의 보존율은 CsA군에서는 $88\%, Tacrolimus에서 $91\%$. 유의한 차이는 없었다(p=0.29). 췌장이식 후 6개월 동안 Tacrolimus의 사용은 생검으로 증명되는(biopsy-proven) 급성 거부반응의 발생빈도는 CsA보다 유의하게 낮았을 뿐만 아니라 (p<0.05) 거부반응 증상의 심각도 또한 감소시켰다 (p=0.03). 급성거부반응 발생빈도의 감소로 Tacrolimus군에서 antilymphocyte 치료가 유의하게 줄어들었다(p=0.01). CsA군에서 Tacrolimus보다 신부전의 발생률이 높았으나 통계학적 차이는 없었다. 췌장이식후의 최적의 면역억제요법의 결정하기 위해서는 향후 Tacrolimus와 CsA을 비교하는 전향적 무작위 연구가 필요하다.

• Journal of Chest Surgery
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• v.33 no.12
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• pp.929-934
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• 2000

배경: 기관의 동종이식편은 초냉동보관으로 생육성을 유지할 수 있으며 항원성이 줄어든다고 알려졌으나 냉동보관 온도 및 기간에 따른 항원성의 변화는 아직까지 명확히 밝혀져 있지 않다. 따라서 이번 연구에서는 냉동보관 온도의 차이 및 기간이 쥐 기관 동종이식편의 거부반응에 미치는 영향을 연구하였다. 대상 및 방법: 24개의 쥐 기관을 적출하여 12개씩 -8$0^{\circ}C$ 냉동고 및 -196$^{\circ}C$ 질소탱크에 각각 1, 3, 6개월씩 보관하였다. 냉동보관한 기관을 반으로 나누어 48마리의 쥐복강에 대망으로 감싼 다음 이식하였다. 1, 3, 5군은 -8$0^{\circ}C$ 냉동고에 각각 1, 3, 6개월씩 보관한 기관 동종이식편을 이식하였고 2, 4, 6군은 -196$^{\circ}C$ 질소탱크에 각각 1, 3, 6개월씩 보관한 기관 동종이식편을 이식하였다. 7군은 대조군으로 냉동보관하지 않은 동종이식편을 이식하였다. 이식후 14일째 이식된 동종이식편을 적출하여 간질조직의 단세포 침윤정도 및 내강 폐쇄 정도를 관찰하여 거부반응을 정도를 측정하였다. 결과: 7개 군 모두에서 중등도 이상의 심한 단세포 침윤을 보였으며 각군간의 통계학적인 차이를 보이지 않았다. 1, 2, 3, 4, 5, 6군에서 7군에서 보다 내강 폐쇄 정도가 적었으나 통계학적인 의의는 없었다. 모든 군에서 연골주위 단세포 침윤이 심한 경우에도 연골세포는 비교적 생육성을 잘 유지하고 있었다. 결론: 냉동보관 온도 및 보관 기간의 차이에 따른 동종이식편의 거부반응의 차이는 없었으며 모든 군에서 심한 거부반응을 보였다. 따라서 냉동 보관 쥐 동종이식편을 이용한 실험에서는 적절한 면역억제제의 사용이 필수적이라고 생각된다.

• Childhood Kidney Diseases
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• v.11 no.2
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• pp.152-160
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• 2007

Twenty-six renal allograft biopsies which showed acute rejection and had renal capsule and medulla in the same specimen were selected in order to compare the severity of acute rejection between superficial cortex, deep cortex and medulla. Disregarding the mid cortical region, the superficial cortex was considered as being one-third of the distance from the renal capsule to the medulla and the deep cortex as being that one-third of the cortex which was adjacent to the medulla. Using semiquantitative histologic analysis the following parameters were compared in superficial cortex, deep cortex, and medulla: interstitial inflammation, edema, tubulitis, and acute tubulointerstitial rejection grade. Also, the presence of lymphocyte activation and polymorphonuclear leukocytes was evaluated. Significantly greater histologic changes of acute rejection were found in the deep cortex vs. supeficial cortex for the following parameters: interstitial inflammation(P=0.013), edema (P=0.023) and tubulointerstitial rejection grade(P=0.016). These findings support the view that biopsies in which deep cortex is not included may result in underestimation of the severity of renal allograft rejection.

• Journal of Chest Surgery
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• v.31 no.12
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• pp.1127-1133
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• 1998

Background: There are no ideal substitutes for tracheal replacement. Therefore we investigated the possibility of clinical use of cryopreserved tracheal homograft with special interest in the viability and rejection of the epithelial cell and cartilage. Material and Method: Rabbit's trachea was sected and stored in liquid nitrogen tank for 1 month. Tracheal replacement was done in 45 rabbits with autograft(n=15, Group 1), fresh allograft(n=15, Group 2) and cryopreserved homograft(n=15, Group 3). After 7, 14, and 30 days, 5 rabbits in each group were sacrificed and the regeneration of epithelium and cartilage and the degree of rejection were assessed by counting the monocellular infiltration. Result: Investigation at day 7, showed no difference in epithelial regeneration, however, at days 14 and 30, Group 1 showed better regeneration of epithelium than groups 2 and 3. There was no difference of epithelial regeneration between group 2 and 3. There was little rejection at day 7, but at days 14 and 30, there was significant rejection in group 2 and group 3.(P<0.05). Group 3 showed lesser rejection than group 2 at days 14 and 30, but it was not statistically significant. Cartilage showed no rejection and maintained its viability in groups 2 and 3. Conclusion: Cryopreserved tracheal homograft can maintain its viability, therefore it may represent a possibility of clinical application for tracheal replacement. However, cryopreservation can not eliminate the antigenicity of the trachea completely. Furthere studies for lowering the antigenicity and rejection should be performed for an ideal substitute for tracheal replacement.

• Journal of Chest Surgery
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• v.36 no.6
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• pp.379-383
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• 2003

Background: An accurate diagnosis of the severity of the rejection after a heart transplantation relies on endomyo-cardial biopsy, but because of its invasiveness and the need for repeated examination makes it is an inappropriate monitoring method. Therefore, we have tried to find a monitoring method that is continuous and less invasive. Material and Method: Heterotopic heart transplantation using Ono-Lindsey Method was done in 20 rats, and then $^{99m}$ Tc-Pyrophosphate (PYP) scan was done after a month, Uptake ratio of transplanted heart to vertebrae (H/V) was obtained to be compared with the biopsy result. Result: Rejection was defined when the H/V uptake ratio was higher than 0.09, and we compared the uptake ratio with the results of biopsy. The result was true positives was 3, true negatives 12, false negatives 2, andfalse positives 3. Therefore sensitivity was 60% and specificity was 80%, diagnostic value was 75%. Conclusion: $^{99m}$Tc-Pyrophosphate (PYP) scan was a useful method for the evaluation of the heart transplantation rejection and it will be helpful for monitoring rejection as an non-invasive and simple method.hod.

• Journal of Chest Surgery
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• v.29 no.3
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• pp.322-325
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• 1996

ABO incompatible allografting is contraindicated in most organ transplantations including heart because of the hyperacute and acute rejections caused by preexisting antibodies. However several reports showed that ABO incompatible organ transplantation could be managed successfully by plasmapheresis, antibody adsorption, immunosuppression, splenectomy, and so on. We experienced one success in ABO incompatible cardiac transplantation by means of plasmapheresis and immunosuppression. However, this does not justify heart transplantation across ABO blood group barriers. Because the effect of ABO incompatibility on continued acute rejection or chronic rejection has not been fully understood, long-term follow-up study is required.

• Journal of Veterinary Clinics
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• v.22 no.4
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• pp.322-327
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• 2005

DLA class I complement-dependent cytotoxicity (CDC) cross-match method was established to control hyperacute rejections in organ transplantation. The aim of the present study is to investigate if DLA class 1 CDC corssmatch method is effective to prevent hyperacute rejections in canine renal allografts. Seven mongrel dogs of similar age and weight were used. Erythrocyte crossmatch was first performed and only the negatives were used. Among the same blood types, CDC cross-match was performed. Anti-dog serum, Hank's balanced salt solution(HBSS), and tile self-serum was used as a positive-, a negative-, and all auto-control respectively. After the reaction with class I complement, it was stained with eosin and scored by international cytotoxicity scoring system under inverted phase microscope. According to these results, kidneys oi CDC negatives among same blood types were cross-transplanted to observe the incidence of hyperacute rejections. One of four 1.2 B blood type dogs had autoantibodies. here were negative CDC results among each blood type, and also there were negative results between different blood types. Two pairs with the same blood types and negative CDC results underwent allo-transplantation each other. There were no hyperacute rejections. DLA cross-match method studied in this experiment for canine renal allograft can be effective to prevent hyperacute rejections. it may be applicable for the future studies of histocompatibility testing in canine renal allografts.

• Radiation Oncology Journal
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• v.4 no.1
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• pp.15-20
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• 1986

From 1979 to 1984, 39 local allograft irradiations were given to 29 patients: 10 irradiations were administered for prevention and 29 for reversal of acute rejection of transplanted kidney. Three doses of 150 cGy every other day were combined with high-dose of methylprednisolone pulse (1 gm/day) for 3 days. For prevention of acute rejection, local irradiation was delivered on the days 1, 3, and 5 after the transplantation, and for reversal, irradiation started after the diagnosis of acute rejection. Eight out of 10 patients irradiated for prevention had acute allograft rejection, and, what is more, there was no surviving graft at 15 months after transplantation. Reversal of acute rejection was achieved in $71\%$. When the pre-irradiation level of serum creatinine was below $5.5mg\%$, the reversal rate was $93\%$, but above $5.5mg\%$ the reversal rate was only $17\%$ (p<0.01). Reirradiation after failure was not successful. Among 15 reversed patients, $7(47\%)$ had subsequent rejection (s). The functional graft survivals at 6 month, 1, 2, and 3 year were $70\%,\;65\%,\; 54\%,\;and\;54\%$, respectively. Therapeutic irradiation resulted in better graft survival when serum creatinine was below $5.5mg\%$ (p<0.001) or when irradiation started within 15 days after the diagnosis of acute rejection (p<0.001).

• Journal of Chest Surgery
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• v.43 no.6
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• pp.734-738
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• 2010

A 43 year-old female, who underwent bilateral lung transplantation for Eisenmenger syndrome 10 years previously, visited our hospital complaining of progressive severe dyspnea. She was diagnosed as having. bronchiolitis obliterans syndrome, which was presumably caused by chronic graft rejection following lung transplantation. Due to the aggravated dyspnea despite medical treatment, she required ventilator care and then she underwent lung retransplantation. We report here on a case of lung retransplantation for treating chronic graft rejection following the previous lung transplantation for the first time in Korea.

• Journal of Chest Surgery
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• v.37 no.5
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• pp.391-400
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• 2004

Xenotransplantation in discordant species results in immediate and irreversible hyperacute rejection due to natural antibodies, IgM. With this, antibody depletion is one option to reduce hyperacute rejection, we investigated the effect of PCPP (postcentrifugal plasmapheresis) on the depletion of natural antibodies and the effect of antibody titer on xenograft survival. Material and Method: Outbred swines (n=4) weighing 10∼20 kg were used as donors and mongrel dogs (n=4) weighing 25∼30 kg were used as recipients. Recipient canines underwent plasmapheresis (COBE TPE Laboratories, Lakewood. CO, USA). Pre-transplantation PCPP was peformed on day －2 and day 0. There were three groups (Group 0: no PCPP, Group 1: 1 pla sma-volume (PV) at day －2 and 2 PV at day 0, Group 2: 2 PV at day －2 and 2 PV at day 0). A swine heart was heterotopically transplanted into a recipient's abdominal infrarenal aorta and inferior vena cava. Mean percent depletion of total IgM and IgG in plasma of the recipients was calculated. Serum albumin, electrolyte, complement activity and coagulation factors were measured. Histopathologic examination of heart specimens was performed. Result: Mean percent depletion of IgM and IgG were 95.7$\pm$1.2%, 80.5$\pm$2.4% in the group 2 at the end of PCPP. The percent depletion of serum albumin concentration was decreased from 2.8 to 1.4 g/㎗ in the group 1 and 3.0 to 1.5 g/㎗ in the group 2. Complement hemolytic activity was decreased in group 1 and 2, but returned to normal level within 24 hours. Complement hemolytic activity was reduced to 10% of pre-PCPP level in group 2. Serum fibrinogen decreased to 20% or less and was recovered within 24 hours in group 2. Antithrombin III decreased but less than fibrinogen. PT and aPTT were sometimes but not always prolonged during plasmapheresis. After plasmapheresis, PT and aPTT were prolonged beyond the measurable level. D-dimer was not found during PCPP, but appeared and maintained from 10 minutes after trasplantation. Graft Survival time was 5 min in group 0, and it was 90$\pm$0 min in the group 2. Histopathologic changes were more typically characterized by edema, hemorrhages, thrombosis in all groups at the end of experiment. Conclusion: PCPP effectively removed immuoglobulins and reduced the titer of natural antibodies, as a result, significantly prololonged swine heart xenograft survival.