Synergistic effect of donor-specific blood transfusion and a short course of deoxyspergualin in rat kidney transplantation

Deoxyspergualin (DSG), an analogue of spergualin produced by B. laterosporus, has a strong immunosuppressive effect in various transplantation models. We have investigated the mechanism of donor-specific prolongation of survival time in rat kidney grafting by donor-specific blood transfusion (DST) and a short course of DSG. Lewis (LEW) kidney allografts were transplanted into fully allogeneic BN rats. Fresh, whole LEW blood 1.0 ml, was injected i.v. into BN rats 2 days prior to transplantation. Then, DSG, 6 mg/kg per day, was administered by i.m. injection on days 0, 1, and 2 after transplantation. The recipients were divided into five groups: group 1 (n=6) no treatment: group 2 (n=6) DST only; group 3 (n=7) DSG only; group 4 (n=7) DST and DSG; and group 5 (n=6), third party (ACI rats) blood transfusion and DSG. Lymphocytes (cervical lymph nodes) and serum were harvested from BN recipients on day 7 postgrafting. For suppressor cell assays, lymphocytes from BN recipients in each group were added as a third cell to the mixed lymphocyte reaction (MLC) between nontransplanted BN lymphocytes (responder) and LEW or other third party (PVGC, ACI, WKA rats) lymphocytes (stimulator). Antidonor lymphocytotoxic antibody (ADLA) was checked by microcytotoxicity assays. Median survival times (MST) for each group were: group 1, 10 days; group 1, 10 days; group 3, 13 days; group 4, 75 days; and group 5, 13 days. Remarkable prolongation of MST was only noted in group 4. In the suppressor cell assay, group 4 showed significant suppression (40%; P<0.05); the other groups did not show any suppression. This suppressive activity in group 4 was effective only during the MLC between BN and LEW, not during the MLC of third party-BN combinations. Thus, suppressor cells from DST/DSG-treated BN recipients appear to be donor-specific. In the microcytotoxicity assay, the only group that showed any ADLA was group 2, which was not treated with DSG. These results clearly show that both induction of donor-specific suppressor cells and inhibition of ADLA production are associated with the remarkable donor-specific prolongation of kidney allograft survival in DST/DSG-treated recipients.     

The superior effect of the combination of FK 506 and deoxyspergualin on rat cardiac allograft survival

In this present study, the effects of FK 506 and 15-deoxyspergualin (DSG), with respect to dose, timing, and combination, were investigated in an ACI-to-LEW rat cardiac allograft model. FK 506 was adminstered intramuscularly for 14 days starting on day 0 after grafting, while DSG was given intraperitoneally for 7 days starting on day 0,4, or 7 after transplantation. FK 506 or DSG monotherapy prolonged cardiac allograft survival in dose-dependent manners, and the minimum effective dose for overcoming rejection was 0.1 mg/kg per day in the case of FK 506 and 1.0 mg/kg per day for DSG. The graft survival rate was higher with administration of DSG starting on day 4 on day 0 after transplantation. A low dosage of FK 506 strating on day 0, in combination with DSG starting on day 0 or day 4 (but not on day 7), had a synergistic effect in prolonging allograft survival for 14.0±3.3 days and 25.4±8.2 days, respectively. The most effective combination treatment schedule for prolongation of allograft survival was FK 506 starting on day 0 and DSG starting on day 4 after transplantation.     

Effect of plasma exchange in combination with deoxyspergualin on the survival of guinea-pig hearts in macrophage-depleted C6-deficient rats

The present study aimed to evaluate the effect of plasma exchange (PE) in combination with certain immunosuppressive agents on the survival of guinea-pig hearts in C6-deficient (C6-) rats. To deplete macrophages, we gave liposome-encapsulated dichloromethylene diphosphonate (Lip-Cl2MDP) intravenously (i.v.) in a dose of 10 mg/kg on day 2 before transplantation and every 5 days until rejection. Deoxyspergualin (DSG) was also given i.v. in a dose of 10 mg/kg/day from day -2 until rejection. Plasma exchange was performed 1 day before xenografting. All animals were splenectomized just before heart transplantation. Heart xenografts were evaluated twice daily and harvested at the time of rejection. The serum levels of anti-guinea-pig xenoreactive antibody (IgM, IgG) were measured using enzyme-linked immunosorbent assay (ELISA). Graft survival was 2.8 +/- 0.5 days in control rats, and 4.0 +/- 0.3 days with PE alone. A combination of PE with Lip-Cl2MDP or DSG did not improve the results (4.2 +/- 0.6 days vs. 4.8 +/- 0.6 days, respectively). While in rats treated with PE and the combination of Lip-Cl2MDP and DSG, graft survival was significantly prolonged (6.9 +/- 1.1 days, P < 0.01 vs. controls). In untreated control rats, xenoreactive antibody (IgM, IgG) levels decreased immediately after PE, but their levels rapidly returned to normal. In rats treated with DSG or DSG + Lip-Cl2MDP, the IgM levels remained low during the observation period. Immunohistochemistry showed that macrophage infiltration into the graft was suppressed in Lip-Cl2MDP-treated groups at the time of rejection. Our results demonstrate that sustained suppression of antibody levels can be achieved by PE in combination with DSG and xenograft survival is further prolonged in macrophage-depleted C6- rats. These findings suggest that strategies targeting antibody and macrophages may be useful in prolonging xenograft survival.     

Treatment with total lymphoid irradiation,cyclosporin A and a monoclonal anti-T-cell antibody in a hamster-to-rat heart transplantation model: Graft survival and morphological analysis

Treatment with preoperative total lymphoid irradiation and post-transplant cyclosporin A has been shown to have a synergistic effect on graft survival in allo-and xenotransplantation. Specific monoclonal antibodies against T cells and T cell subpopulations could offer new ways of preventing graft rejection in xenotransplantation. Graft survival and histology were examined after total lymphoid irradiation plus cyclosporin A treatment versus cyclosporin A plus a monoclonal antibody in a concordant, heterotopic, hamster-to-rat heart transplantation model. Preoperative total lymphoid irradiation was given at a dose of 1.25 Gy, 12 times over a period of 3 weeks. Cyclosporin A at a dose of 12.5 mg/kg per day was administered perorally and OX-19, a pan T cell monoclonal antibody, was given as intraperitoneal injections at doses of 100 g or 500 g/kg per day from day 0 until graft rejection. While total lymphoid irradiation alone prolonged graft survival to 9.4 days, total lymphoid irradiation plus cyclosporin A extended graft survival to a mean of 22 days. Cyclosporin alone or combined with the monoclonal antibody could not increase graft survival significantly when compared to untreated animals, which rejected their grafts within 3.7 days. Vascular rejection was the characteristic morphological finding, even after some weeks of excellent graft function. In conclusion, total lymphoid irradiation and cyclosporin A had a synergistic effect on graft survival in this concordant xenotransplantation model, although recent impressive results from other groups could not be reproduced. Total lymphoid irradiation combined with cyclosporin A appears to delay a primary humoral graft rejection, while the mechanism of rejection, judged by histology, stays the same.     

Pre-transplant blood transfusion and cyclosporin A induce long-term hamster cardiac xenograft survival in immunocompetent rats

BACKGROUND: In previous studies we have shown that pre-transplant hamster blood transfusion (HBT) can induce non-responsiveness in the T cell independent immunecompartment and result in tolerance towards hamster cardiac xenografts (Xgs) in T cell deficient athymic nude rats. In this study we test the combination of pre-transplant HBT with cyclosporin A (CSA) in immunocompetent Lewis rats. METHODS: Before transplantation of a hamster cardiac Xg, 1 ml hamster blood was administered to nude rats or Lewis rats. CSA dissolved in olive oil was given orally at varying doses. Anti-hamster antibodies were measured by flowcytometry. RESULTS: In nude rats HBT 3 days before transplantation resulted in 100% long-term survival >100 days (n=9). In Lewis rats, HBT resulted in hyperacute rejection (HAR) (n=6). Treatment of nude rats with CSA at doses varying from five to 20 mg/kg/day and treatment of Lewis rats with CSA five or 10 mg/kg/day did not effect Xg survival. However, treatment of Lewis rats with CSA 20 mg/kg/day led to long-term survival of five of nine Xgs (p <0.01). Combination of HBT with CSA 10 mg/kg/day in Lewis rats resulted in long-term survival of four of seven Xgs. HBT and CSA 20 mg/kg/day resulted in 100% long-term survival (n=9). Immunoglobulin M (IgM) increased after HBT and CSA in these Lewis rats, but decreased after transplantation and remained low over time. When CSA was discontinued, IgM increased and Xgs were rejected (n=3). CONCLUSIONS: This study confirms that pre-transplant HBT results in long-term survival of hamster cardiac Xgs in nude rats. HBT and CSA have strong synergistic effects in immunocompetent Lewis rats. Combination of HBT with CSA treatment leads to long-term Xg survival in Lewis rats, whereas HBT alone results in HAR. The presence of T cells has a dominant influence on Xg survival after pre-transplant blood transfusion.     

Treatment with a short course of LF 15-0195 and continuous cyclosporin A attenuates acute xenograft rejection in a rat-to-mouse cardiac transplantation model

Searching for a novel immunosuppressive agent to effectively prevent acute vascular rejection (AVR) is essential for success in clinical xenotransplantation. We previously reported that Lewis rat hearts transplanted into BALB/c mice developed typical AVR in 6 days. The present study was undertaken to determine the efficacy of LF 15-0195, a new immunosuppressive analog of 15-deoxyspergualin in the prevention of AVR in a rat-to-mouse cardiac xenograft model. We transplanted 2-week old Lewis rat hearts into BALB/c mice. Four groups were included in this study: untreated recipients and cyclosporin A (CsA) treated recipients were controls; LF 15-0195 treated recipients or LF 15-0195 combined with CsA treated recipients were experimental groups. Mouse recipients received either LF 15-0195 2 mg/kg subcutaneously from day-1 to post-operative day 14, or CsA 15 mg/kg subcutaneously daily, from day 0 to endpoint rejection, or the two drugs in combination. We observed that high dose CsA did not inhibit AVR and the graft was rejected in 11.3 +/- 1.9 days. Graft histology and immunohistology showed typical AVR, characterized by interstitial hemorrhage, intravascular fibrin deposition, thrombosis, and massive deposition of anti-rat immunoglobulin G (IgG) and immunoglobulin M (IgM). Serum xenoreactive antibodies (xAbs) were markedly elevated in these animals as well. In contrast, we observed that treatment with LF 15-0195 alone significantly prolonged graft survival to 19.3 +/- 0.7 days. Notably, xAbs were significantly decreased and the rejection pattern of these grafts was cell-mediated rejection (CMR), instead of AVR. When CsA was combined with LF 15-0195, the graft mean survival time was further increased to 58.5 +/- 17.3 days. Antibody production and T-cell infiltration were significantly inhibited at the terminal stages of graft survival and pathology showed striking attenuation of both AVR and CMR. Sequential studies on days 6 and 14 demonstrated that LF 15-0195 either alone or combined with CsA completely inhibited antibody production. However, intragraft infiltration by Mac-1 positive cells including natural killer cells, macrophages and granulocytes in LF 15-0195 treated recipients was similar to that of untreated recipients. We conclude that LF 15-0195 effectively prevented AVR by markedly inhibiting the production of anti-donor IgG xAbs. Also, treatment with short course LF 15-0195 and continuous CsA significantly reduced T-cell infiltration. Studies to test this therapy in inhibiting AVR in a pig-to-non-human primate xenotransplantation model are underway.     

Effect of cyclosporin on lung diffusing capacity in renal transplant patients

A prospective lung function study pre- and postrenal transplantation was performed on 21 patients in order to evaluate whether cyclosporin decreased the lung diffusing capacity due to lung toxicity. Initial inclusion criteria were absence of respiratory symptoms and normal findings in both chest X-ray and pulmonary function tests. Participants had to be nonsmokers. We determined spirometry including lung volumes, arterial blood gases, carbon monoxide diffusing capacity by the single breath method (D_LCO_SB), and rate of CO uptake per unit of lung volume (KCO) before and 3, 6, and 12 months after transplantation. Immunosuppression consisted of prednisone and cyclosporin, maintaining total blood levels between 100 and 250 ng/ml. Spirometric and blood gases data remained within reference levels during the follow-up. Hemoglobin (Hb) pretransplant concentrations remained low, returning to their normal levels posttransplantation. Pretransplant D_LCO_SB levels were slightly decreased but fell within the therapeutic range after correction for Hb concentration, unlike the mean KCO levels which remained slightly diminished despite their correction. In post-transplant controls, the values obtained for both D_LCO_SB and KCO were significantly higher at the different post-transplant intervals (P<0.005) than pretransplantation but only when compared without Hb correction. No significant differences for D_LCO_SB were found when corrected values were compared, and an improvement in the KCO appeared to be significant at 12 months posttransplantation. Based on these findings, we feel that when serum levels are within the therapeutic range, cyclosporin fails to alter the respiratory function or the pulmonary diffusing capacity of the lung.     

A pharmacokinetic comparison of cyclosporin oral solution and cyclosporin capsules in heart and lung transplant recipients

Pharmacokinetic profiles were obtained for 16 heart or lung recipients following the administration of identical doses of cyclosporin as oral solution and capsules on consecutive days. A comparison of pharmacokinetic parameters (AUC, C_max, C_min and t_max) showed that there were no significant differences between the two formulations except for the t_max, which was significantly longer for the capsules. The mean variation in day-to-day trough levels produced by the two different forms was 25.6%. A retrospective study was carried out of consecutive cyclosporin levels in patients at steady state on oral solution. The mean variation in day-to-day trough levels was 32.3%. This was not significantly different from the variation in consecutive trough levels seen in the oral solution/capsule comparison. This study shows that cyclosporin capsules can be substituted for oral solution without causing acute changes in cyclosporin blood levels, and that the pharmacokinetics of the two formulations are similar.This work was carried out in partial fulfillment of the requirements for the Master of Science Degree in Clinical Pharmacy, University of London     

Xenotransplantation of microencapsulated pancreatic islets contained in a vascular prosthesis: preliminary results

Porcine and human pancreatic islets were microencapsulated in an alginate-polylysine biomembrane and put in a chamber of a new vascular prosthesis composed of an inner tubing of Dacron mesh and an outer tubing of expanded polytetrafluorethylene material. The vascular prosthesis was anastomized between the iliac artery and the contralateral vein of diabetic dogs. The recipients did not receive any immunosuppressive therapy. Function of porcine and human islets was monitored by measuring serum glucose levels and human C-peptide concentrations. After transplantation, serum glucose levels were maintained at values lower than 200 mg/dl, and C-peptide concentrations were between 0.8 and 3.2 ng/ml. Injected insulin requirements decreased by 50%–60%. Four to 8 weeks after transplantation, histologic examination showed well-preserved and functioning islets in the majority of intact microcapsules. Fibrin and inflammatory cells were not observed in the chamber. These data suggest long-term survival and function of microencapsulated pancreatic islets in the vascular prosthesis.     

大鼠右肺原位移植模型的建立

目的 探讨建立大鼠右肺原位移植模型的手术技术,以及该模型应用于缺血再灌注损伤研究的可行性.方法 选用纯种雄性SD大鼠(体重250～270 g)作为肺移植模型的供、受者.供、受者的手术均在手术放大镜下进行,由同一操作者连续完成大鼠右肺原位移植模型12例.供者全身麻醉后行机械通气,正中切开胸腹暴露心脏和双肺,下腔静脉注射肝素,切开右室流出道和左心耳放血后将灌注管插入肺动脉内行肺灌注,灌注完成后切取并保存供肺.右肺移植时,受者全身麻醉和辅助呼气方法同供者.右后外侧第4肋间切口入胸,游离并从远端切断肺血管和支气管,将供肺植入受者胸腔后,分别吻合支气管及肺动、静脉.观察受者术中及术后的情况.结果 供肺平均冷缺血时间为(131.25±20.24)min;平均移植时间为(91.25±15.97)min.开放循环后24 h,共有8只受者存活,手术成功率为66.7%.有6只受者存活时间超过4周.结论 大鼠右肺原位移植模型难度较大,但它是一种新型的适用于肺移植缺血再灌注损伤研究的动物模型.     

Transimission of donor lymphocytes in clinical lung transplantation

Passenger mononuclear cells in organ grafts are known to influence the alloimmune response to the graft. To assess their relevance in clinical lung transplantation, we studied the amount, distribution, cell types, and surface marker expression of mononuclear cells in human donor lungs. Two major compartments of mononuclear cells could be differentiated: lymph nodes containing resting T and B lymphocytes, and the lung tissue itself, containing mainly activated lymphocytes as well as monocytes/macrophages. Tissue-associated mononuclear cells make up 20–40x10⁹ cells per lung, about 30–50 % of which are lymphocytes. Tissue-associated lymphocytes are predominantly T and NK cells; most of the T cells are CD8⁺ CD45R0⁺ and express HLA-DR. Strong expression of the adhesion molecules LFA-1 and ICAM-1 is present on infiltrating cells as well as on resident cells of the organ. Moreover, the lymphocytes inside the lung tissue are functionally highly active, with a strong stimulatory as well as alloreactive potency. Thus, large numbers of allogeneic mononuclear cells and particularly large numbers of functionally active lymphocytes are obviously transmitted by human lung allografts. The immunological in vivo relevance of these cells after lung transplantation may include allostimulation and graft-versus-host activity, but also beneficial immunomodulatory effects.     

羟喜树碱和环孢素A对异基因大鼠心脏移植物急性排斥反应的协同抑制作用

目的 探讨羟喜树碱（OPT）和环孢素A（CsA）对异基因心脏移植物急性排斥反应的协同抑制作用。方法 以纯系SD大鼠为供者,纯系Wistar大鼠为受者,行异体颈部异位心脏移植。40只受者大鼠心脏移植后随机分成4组。A组接受安慰剂。B组接受 OPT1.0mg·kg-1·d-1,腹腔注射。E组接受CsA　10mg·kg-1·d-1,导管灌胃。F组联合应用OPT和CsA,方法剂量同B、E组。结果A组平均存活期为（6.05±0.76）d,B组为（11.45±1.99）d,E组为（14.45±4.85）d,F组有5只大鼠平均存活期为（45.00±19.43）d,另5只大鼠在移植60d后停用OPT和 CsA,存活期超过730 d,并经试验证明形成特异性免疫耐受。结论OPT和CsA的联合应用显著降低异基因大鼠心脏移植物急性排斥反应,明显延长心脏移植存活期。     

Prolongation of heart allograft survival in rats by interferon-specific antibodies and low dose cyclosporin A

Interferons (IFNs) are important cytokines which exhibit antiviral, antitumor, anticellular, as well as immunoregulatory activities [1]. Among these multiple activities, IFNs are potent inducers of MHC antigen expression of a great variety of cells [2–4], helper and maturation factors in B-cell antibody production [5], and macrophage function [6]. IFNs may therefore play a critical role in triggering antigen recognition and allograft rejection. Cyclosporin A (CyA) is a potent immunosuppressor which selectively inhibits helper T-lymphocyte proliferation in response to alloantigen presentation [7, 8]. CyA has been reported to inhibit interleukin 2 and IFNγ production by helper T lymphocytes [9–11]. In addition, CyA may induce monocyte production of prostaglandin E2 [12], which then reduces MHC class II expression on endothelial cells, monocytes, and macrophages [13]. However, the clinical use of CyA is plagued by its toxic (in particular nephrotoxic) side-effects. These toxic effects are clearly dose-related. It may be very important to develop new products which can act synergistically with CyA to inhibit lymphokine production. The aim of this study was to investigate the effects of combined IFN-specific antibodies and low dose CyA on cardiac allografts in inbred strains of rats.     

Enhancement of the immunosuppressive effect of cyclosporin A by ciprofloxacin in a rat cardiac allograft transplantation model

Ciprofloxacin hyperinduces interleukin-2 production in stimulated human and mouse lymphocytes. In this study, an enhanced and prolonged interleukin-2 response was also detected in polyclonally stimulated rat splenocytes in the presence of ciprofloxacin (5–80g/ml) compared to control cells without any antibiotic. Ciprofloxacin was able to counteract the immunosuppressive effect of 10ng/ml cyclosporin A (CyA) but did not interfere with higher CyA concentrations. In parallel, ciprofloxacin did not influence thymidine uptake in mixed lymphocyte reactions in the presence of CyA. To obtain an in vivo application of these findings, graft survival was studied by performing rat cardiac allograft transplantations in the presence or absence of CyA. Brown Norway rats served as donors and Wistar Furth rats as recipients. Ciprofloxacin was injected intraperitoneally either at a high-dose regimen (240 mg/kg per 24h) into rats every 8th h starting 1 day before transplantation until day 21 or graft loss, or it was injected at a low and clinically relevant dose regimen (45mg/kg per 24h) until day 9. CyA was administered orally (10mg/kg per 24h) from day 1 through day 9. Ciprofloxacin given alone at a high-dose regimen resulted in a median graft survival of 14.8 days, which was significantly longer than graft survival in rats without treatment (median 8.0 days). A low-dose regimen of ciprofloxacin alone did not affect graft survival. Ciprofloxacin at a highdose regimen combined with CyA prolonged graft survival to a median of 24.0 days compared to 20.5 days with CyA alone. Ciprofloxacin administered in the drinking water (200mg/kg per 24h) until day 9 in addition to CyA did not affect graft survival. However, when the same dose regimen was used in experiments with PVG rats as donors and Wistar/Kyoto as recipients, graft survival was significantly prolonged to a median of 45 days. Ciprofloxacin, given orally without the addition of CyA, did not influence graft survival in either of the two strain combinations. Thus, our data show that ciprofloxacin has no negative impact on heart graft survival rats. It remains to be clarified whether ciprofloxacin influences graft survival in humans.     

Effects of cyclosporin A on the blood flow of the native and transplanted rat pancreas and duodenum

The aim of the present study was to evaluate the effects of cyclosporin A (CyA) on the blood perfusion of the transplanted pancreas. For this purpose syngeneic pancreaticoduodenal transplantations were performed in Wistar-Furth rats. After nephrectomy the graft was anastomosed using a nonsuturing cuff technique to the left renal vessels. Beginning 7 days after transplantation and then continuing for 2 weeks, CyA (15 mg/kg body weight) or vehicle was given p.o. once daily, 6 days a week. The serum CyA concentrations were greater than 600 ng/ml at all points in time tested. Intraperitoneal glucose tolerance tests were normal in CyA-treated animals after 12 days, but the pancreatic insulin concentration was decreased to the same extent in the native and transplanted pancreas. A microsphere technique was used to measure the blood perfusion of the pancreaticoduodenal graft, the native pancreas and duodenum, and remaining kidney 14 days after starting the CyA treatment. The renal blood flow was markedly decreased by CyA when compared with the control animals. In rats given vehicle alone, pancreatic, islet, and duodenal blood flows were higher in the graft than in the corresponding native organs. However, in rats given CyA, hyperperfusion of the graft was not observed. We conclude that the administration of CyA prevents the transplantation-induced blood flow increase seen in pancreaticoduodenal grafts of vehicle-treated rats. These observations may reflect graft denervation.     

Influence of liver transplantation and cyclosporin on bile secretion —an experimental study in the rat

Bile secretion is reduced after liver transplantation. It has been suggested that this is due either to the effect of cyclosporin or to the damage to the liver graft during preservation and reperfusion. The aim of this study was to explore the influence of cyclosporin as well as of liver transplantation on bile secretion. Bile flow was studied in an experimental model in the rat. In syngeneic liver-transplanted animals, the bile flow was increased compared to the bile flow in the control group (1.29±0.09 ml/h vs 0.66±0.03 ml/h; P<0.01), mainly due to an increased bile acid-independent flow (0.76 ml/h vs 0.50 ml/h; P<0.01). The findings in the livertransplanted rats contrasted with those in a group of nontransplanted animals treated with cyclosporin. Cyclosporin treatment resulted in a reduced bile acid-independent fraction (0.37 ml/h vs 0.50 ml/h, P<0.05) of the bile flow, although no biochemical signs of hepatotoxicity were present. This reduction in the bile acid-independent fraction could, however, not be demonstrated when cyclosporin was given to a group of liver-transplanted rats, although a reduced total bile flow was recorded in the 1st hour measurements. In contrast to previous studies, we found that the cyclosporin vehicle (Cremophor EL), when administered chronically, induced a higher bile flow than that in the control rats. This effect was not seen in the transplanted rats. Our findings in this experimental rat model indicate that cyclosporin will influence and reduce bile secretion and bile acid secretion even if no other signs of liver dysfunction are present. On the other hand, the preservation and reperfusion in this model resulted in an increased bile flow, while bile acid secretion remained constant.     

肺部超声联合血浆SDC-1评估双肺移植术后患者血管外肺水状态

目的探讨应用肺部超声技术结合血浆多配体聚糖-1(SDC-1)对于双肺移植术后患者肺水肿严重程度的评估。方法选择2017年至2018年在南京医科大学附属无锡市人民医院行双肺移植手术患者50例,术中均放置Picco导管,术后入ICU 2 h后由1名医师监测Picco指标血管外肺水指数(EVLWI)和肺血管通透指数(PVPI)。同时由另1名医师进行床旁肺部超声检査,在肺部超声常规检测位点(上蓝点、下蓝点、膈肌点、Plaps点、后蓝点)进行检测,监测B线数目,然后计算总和。随后该医师采用ELISA法测定血清中SDC-1水平。结果双肺移植患者EVLWI同超声B线数目及血浆SDC-1水平均呈正相关(Pearson相关系数RS分别为0.833、0.747,P<0.05),PVPI同B线数目及血浆SDC-1水平同样均呈正相关(Pearson相关系数RS分别为0.738、0.626,P<0.05)。结论超声检测的B线数量及血浆SDC-1水平与双肺移植术后患者的血管外肺水状态有着良好的相关性,将两指标联合应用可作为评估双肺移植术后肺水肿程度的可靠依据。     

Polyarteritis nodosa type vasculitis in a patient with familial Mediterranean fever treated with cyclosporin A

Patients with amyloidosis secondary to familial Mediterranean fever (FMF) are known to tolerate cyclosporin A poorly. We report a case of severe cyclosporin toxicity in a patient with FMF amyloidosis who underwent kidney transplantation. The clinical syndrome consisted of severe gastrointestinal, neuromuscular, and psychiatric disturbances. Histological examination of the transplanted kidney revealed vasculitis of the polyarteritis nodosa type. We hypothesize that FMF patients are more vulnerable to the acute vascular toxicity of cyclosporin due to defective inhibition of complement activation, leading to a widespread vasculitis of the polyarteritis nodosa type.     

大鼠自体左肺原位移植模型的建立

目的　建立大鼠自体左肺模拟原位移植模型 ,探讨缺血 -再灌注 (IR)对移植肺功能损伤的可能影响。方法　模拟临床肺移植建立大鼠自体左肺原位移植模型。分别于游离左肺门 (对照组 )、缺血 4小时 (缺血组 )和缺血 4小时再灌注 4小时 (IR组 )后测定动脉血氧分压 (Pa O2 )、动脉血二氧化碳分压 (Pa CO2 )、气道峰压 (Paw)及支气管肺泡灌洗液 (BAL F)中蛋白含量和左肺含水量 ,并取左肺组织作病理学观察。　结果　所有动物术后均存活。 Pa O2 、Paw、BAL F蛋白含量及左肺含水量 ,IR组与对照组和缺血组之间比较差别均有显著性意义 (P<0 .0 1) ;3组间 Pa CO2 无明显差别 (P>0 .0 5 ) ;IR组病理改变最严重。　结论　该方法的建立为研究 IR对移植肺损伤机制提供了较为理想的动物模型。