心臓移植は，すでに欧米では末期的心および呼吸不全患者の外科的治療として定着し，外科的治療として確立しつつある．1997年に施行された臓器移植法は，6歳未満の脳死判定基準がないこと，15歳以下の臓器提供の意思が認められないことから，小児は心臓移植を受けるチャンスは極めて低く，多くの小児が海外で心臓移植を受けていた．このような現状を打開するために，改正臓器移植法が2010年7月17日に施行され，脳死臓器提供者の年齢制限がなくなった．その結果，2013年末までに6名の児童（6歳未満1名，10〜16歳3名，15〜17歳2名）の脳死臓器提供があり，6名の児童が国内で心臓移植を受けることができたが，身体の小さな小児や，拘束型心筋症など医学的緊急度2の状態で，心臓移植を受ける必要のある小児は，いまだに海外に一縷の望みをかけて渡航しているのが現状である．ここでは，わが国の小児心臓移植の現状を紹介するとともに，小児心臓移植の適応，移植後の管理について概説する．
PURPOSE:FTY720 is a novel immunosuppressive agent that is thought to reduce the number of peripheral blood lymphocytes (PBL) by directing them toward secondary lymphoid organs such as the lymph nodes and Peyer's patches. We studied the effects of FTY720 on aly/aly mice that do not have either lymph nodes or Peyer's patches, as well as on splenectomized aly/aly mice.METHODS:FTY720 was orally administered by gavage (1 mg/kg) to aly/aly mice as well as to aly/+ mice with and without a splenectomy on 14 consecutive days. The number of lymphocytes was then counted using True Cell beads and flow cytometry. The number of B220-, CD3-, and CD4-positive cells was also determined. In addition, skin grafts from C3H donor mice were performed on these mice.RESULTS:FTY720 was effective in significantly reducing the total lymphocyte count as well as the B220-, CD3-, and CD4-positive subtypes in the peripheral blood of aly/+ mice as well as in aly/aly mice with and without a splenectomy. While we did observe allograft skin graft rejection in both the aly/+ mice as well as the aly/aly mice recipients and splenectomized aly/aly mice, the graft survival was prolonged in all groups. The skin allografts treated by FTY720 thus demonstrated fewer lymphocytic cells and less infiltration of CD4-positive cells.CONCLUSIONS:The administration of FTY720 to mice without lymph nodes, Peyer's patches, or spleens still results in peripheral lymphopenia. In all groups, FTY720 was found to prevent the infiltration of CD4-positive cells in skin allografts while also prolonging skin allograft survival. The fate of these lymphocytes, however, is unclear.
The University of Wisconsin (UW) solution has made it possible to extend the limit of liver preservation but primary non-functioning grafts have still been reported. We evaluated their ultrastructural change, high-energy phosphate compound level and electrical impedance at higher frequencies on simple immersion in UW solution for 48 hours preservation. Male Wistar rats (n=6) were used. The livers were removed and immediately immersed in UW solution at 4 degrees C. ATP was determined with a high-pressure liquid chromatograph. Electrical impedance was measured using a 4184A impedance analyzer. Mitochondrial morphological changes were assessed by grading according to Flameng's mitochondria score. Maximum values of tan delta (tan delta m) at each time-point were expressed as percentage of tan delta m, immediately after the begining of preservation, % tan delta m decreased with the time of the preservation up to 36 hours and represented a point of inflection of % tan delta m, coincided with the time when sinusoidal endothelial cell membranes were partially disrupted and the mitochondria score rose to 2 or more. Furthermore, % tan delta m and % ATP, percentage of RTP immediately after the beginning of preservation, content showed a significant correlation. No significant increase in water content was noted. These findings is worth while investigating the function of the transplanted liver.
This report is to revise the initial report originally issued in this journal of Vol. 32, Ne. 3, 1997 which was used for new drug approval(NDA) purpose of the drug. After that, there were discussions on usefulness, efficacy and safety during the drug review period. Based on the discussion, it was decided to reevaluate the effect of the drug in this revised report, and a slight addition was made in the discussion part. The reevaluation, however, resulted no changes in the conclusion for the effect of the drug. Graft rejection is a primary cause of loss of graft function, At present, anti-rejection immunosuppressive agents including bolus-steroids, anti-lymphocyte-globulin, muromonab-CD 3 and 15-deoxyspergualin are used for treatment of graft rejection following renal transplantation. However, some patients do not respond to any of the available anti-rejection agents, and progress to refractory rejection. In this study, the safety and efficacy of mycophenolate mofetil (MMF) were evaluated in renal transplant patients suffering from refractory rejection. Patients were eligible if their rejection was biopsy-proven and they had more than a 25% increase in serum creatinine levels over baseline, defined as the lowest level during the two weeks prior to diagnosis. MMF tvas administered for 12 weeks and efficacy was evaluated based on trends in serum creatinin levels, recurrent rejection, and graft and patient survival. Forty-one patients were enrolled in the study. A central pathological review was done of all biopsies utilizing the Banff Classification to confirm graft rejection. Of those assessed, 26 were eligible for efficacy analysis. Eighteen of the 26 (69.2%) demonstrated efficacy with a decrease in serum creatinine, taking into account the diagnosis and baseline levels. Three of the 26 patients (11.5%) eventually last graft function during the 12-week study, and 4 (15.4%) experienced recurrent rejection. All patients survived. The safety profile of all 41 patients was examined, Twenty one patients (51.2%) experienced adverse events. The most commonly reported events were diarrhea in 13 patients (31.7%), anemia in 10 patients (24.4%), leucopenia in 5 patients (12.2%) and loss of appetite and fever in 3 patients (7.3%). Five patients (12.2%) had to discontinue administration due to adverse events. All the events were resolved with treatment. Nine patients (22.0%) suffered from infection thought to be related to MMF. All infections resolved. In consideration of this profile, MMF is thought to be a promising drug not only to treat refractory rejection, but also to prevent: recurrent: rejection episodes, and is expected to contribute to the prolongation of graft survival.
Organ Transplantation Rct was enacted in October 1997 which allowed organ transplantation from a brain dead donor in Japan and four national lung transplant centers were selected in May 1998. Our hospital covers the East half of Japan. There was no data to estimate lung transplant candidates based on an actural hospital survey in Japan. A questionnaire survey was conducted to investigate lung transplant candidate in the Tohoku area and Niigata prefecture. Replies were collected from 85 hospitals (38.3%) and lung transplant candidates in the past two years were 58 cases in this area. The patient numbers of each disease were 15 cases of chronic emphysema, 14 cases of idiopathic pulmonary fibrosis (IPF), 12 cases of primary pulmonary hypertension (PPH), 8 cases of lymphangioleiomyomatosis (LAM), 4 cases of bronchiectasis (BE), 2 cases of Eisenmenger's syndrome and 3 cases of the others. Sixteen patients were already died and present candidates are 30 cases. Eight (57%) cases of IPF died mean 7 months after estimation of indication of transplantation. Two (50%) of BE died mean 3 months, Two (17%) of PPH died mean 15 months, Two (13%) of RE died mean 30 months and no case of LAM died in this survey. II is very difficult to estimate proper transplant window according to obscure Japanese guidelines. We recommend to use International Guidelines for Selection of Lung Transplant Candidates presented br ASTP/ATS/ERS/ISHLT for estimatation of transplant window of an individual patient. According to this study, lung transplant candidates in Japan were estimated 700 cases in each year. Through only 15 departments (15%) provided the information about lung transplantation to the patients in the past, 79 departments (81%) will provide information to the candidates after this new transplant age in Japan.
Effectiveness of allogeneic bone marrow transplantation (BMT) as a curable treatment for chronic myelogenous leukemia (CML) is now generally recognized. For detection and evaluation of bcr-abl chimeric mRNA as a marker of minimal residual leukemia after transplantation, the reverse transcriptase polymerase chain reaction (RT-PCR) technique is of good diagnostic use. Here, we sequentially followed up bcr-abl mRNAs of 36 patients with CML having undergone allogeneic BMT, and results were analyzed for interrelation between the molecular genetic findings and pre-and post-transplant clinical details. Bcr-abl mRNAs were detected in 28(80.0%;) of 35 patients in whom complete remission mas maintained after BMT, especially within 12 months post-transplant in 29 (90.6%) of 32 patients. But the positive rate diminished to 4 of 21 cases (19.0%) at 24 months post-transplant. During follow-up, no patients showed hematological relapse including one patient who developed relapse of CNS leukemia, while Ph-1 chromosome reappeared in one patient. Univariate analysis revealed a significantly greater rate of bcr-abl mRNA conversion to negative at 24 months for patients who were elderly (P = 0.002), had no splenomegaly (P = 0.046), had no ABO mismatch (P = 0.029), had no sex mismatches those were transplanted from female donors to male recipients (P = 0.036), and had received the administration of corticosteroids (P = 0.046). The results suggest that pre-transplant turner burden and post-transplant GVL effect play important rules in persistence of bcrabl mRNA.
