克山病患者心脏移植术后急性排异反应的监测

目的对３例重症克山病患者同种原位心脏移植术后进行监测,探讨心脏移植术后急性排异反应的监测指标。方法监测指标：临床症状;１２导联心电图;超声心动图;单光子计算机体层扫描;外周血Ｔ淋巴细胞检查;心内膜心肌活检;Ｘ线影像。结果行ＥＭＢ１９次,发现１ｂ级和２级各１次,３ａ级２次。３ａ级时ＵＣＧ发现心包积液有增加趋势,其余指标未见明显改变。结论心内膜心肌活检是诊断急性排异反应敏感可靠的指标,其它一些常用的指标不敏感且缺乏特异性,但可做为辅助指标。     

Morphologic studies of intestinal allograft rejection

The usefulness of isolated intestinal pouches of an intestinal allograft for monitoring mucosal histoloty during rejection episodes was studied in a canine model. Total small intestinal autotransplantation was performed in four dogs, and allotransplantation in 18 dogs. Isolated pouches from the proximal and distal ends of the allografts were brought to the skin as stomas. Serial biopsies were obtained from these pouches. Nine allotransplants were treated with a suboptimal dose of cyclosporine. Nine allografied dogs were not immunosuppressed. Biopsies from all animals were normal the first two days postoperatively, and remained so in the autotransplants. Mononuclear cell infiltration in the lamine propria and submucosa was seen up to five days before death from rejection of the allograft in dogs on cyclosporine. At autopsy, all dogs had histologic findings in the transplanted bowel similar to those of simultaneously obtained pouch biopsies. The results show that histologic changes in isolated pouches from intestinal allotransplants reflect changes in the incontinuity segment of the graft and, therefore, such pouches can be used for histologic monitoring of the graft. Read at the meeting of the American Society of Colon and Rectal Surgeons, Boston, Massachusetts, June 5 to 9, 1983. This research was supported by the Division of General Surgery, Toronto General Hospital, the Toronto General Hospital Foundation, the Creenmeadow Charitable Foundation, and the PSI Foundation.     

Plasmapheresis in C4d-positive acute humoral rejection following kidney transplantation: a review of 4 cases

Acute and chronic rejection after kidney transplantation has long been exclusively attributed to cellular and vascular mechanisms. Modern immunosuppressive therapy, therefore, addresses the cellular immune system. Rising experiences in kidney transplantation in the last few decades have revealed that some types of rejection are refractory to the conventional immunosuppressive treatment. Humoral rejection. which has previously been reported as a crucial factor in hyperacute rejection, is now suspected to play also an important role in acute and chronic rejection. Acute humoral rejection (AHR) is characterized by immunohistochemical detection of C4d deposits in peritubular capillaries. As shown for other antibody-mediated diseases, such as some autoimmune diseases, plasmapheresis has been suggested to be an efficient therapeutic approach in AHR. We present four patients with C4d-positive AHR in the early phase after kidney transplantation. In three of the four patients, humoral graft rejection was successfully treated by plasmapheresis. Graft function was significantly improved with a stable long-term outcome. One patient lost the graft. Although the number of patients with C4d-positive AHR treated by plasmapheresis is limited, plasma exchange appears to be an efficient and powerful therapeutic approach to control humoral rejection.     

Changes in transthoracic electrical impedance at high altitude.

Mean transthoracic electrical impedance (impedance) which is inversely related to intrathoracic extravascular fluid volume was measured in 121 normal healthy volunteers at sea-level and at 3658 metres altitude. Fifty (group A) reached the high altitude location after an hour's journey in a pressurised aircraft. Twenty-five (group D) underwent slow road ascent including acclimatisation en route. Thirty permanent residents (group B) and 16 temporary residents at high altitude (group C) were also studied. Serial studies in the 30 subjects of group A who developed symptoms of high altidue sickness showed a significant decrease of impedance up to the fourth day of exposure to high altitude which later returned to normal. The 4 volunteers who developed severe symptoms showed the largest drop in impedance. A case of acute pulmonary oedema developing at 4300 metres showed an impedance value of 24-1 ohms on admission. After effective treatment the impedance increased by 11-9 to 36-0 ohms. Twenty asymptomatic subjects of group A and 25 of group D showed a small average increase in impedance values at high altitude. These obstructions suggest that measurement of transthoracic electrical impedance may be a valuable means of detecting incipient high altitude pulmonary oedema.     

心脏移植受者供心临床心律变化意义的探讨（附三例报告）

结合３例原位心脏移植受者探讨供心临床心律变化的特点。经动态观察发现：２例供心在术中血运再通后出现心室颤动，电除颤后转为窦性心律，１例自行出现窦性心律；１例供心在术后出现一过性ＩＩ度房室阻滞；２例心电图显示双心房心律，１例为单心房心律；３例供心的特殊传导系统能够维持正常功能；发生中、重度急性排斥反应时未出现心律失常。提示单凭体液调控能使供心维持正常心律，心律失常并非急性排斥反应的敏感指标。     

Demonstration of abnormalities of myocardial mitochondrial oxygenation in cardiac graft rejection

Abnormalities of myocardial metabolism during acute rejection may be due to ischemia to primary metabolic changes related to rejection. An experimental study of heterotopic cardiac transplantation in the rat was undertaken to study myocardial mitochondrial oxidation during acute rejection. The receivers were Lewis rats and the donors Fischer (FL: allograft) or Lewis (LL: isograft) rats. The oxygen consumption of the mitochondria (VO2m) isolated from the transplanted and native hearts was measured by oxygraphy six days after transplantation. Using maleate and glutamate substrates, the VO2m of transplanted hearts was significantly lower than that of native hearts in the two groups of rats (FL, p less than 0.01; LL, p less than 0.01). In addition, the VO2m of FL allograft transplanted hearts was significantly lower than in the LL rats (30 +/- 9 vs 100 +/- 15 nanoatoms of oxygen/min.mg/prot, p less than 0.01) as was the VO2m of the native hearts (FL: 106 +/- 23 vs LL: 164 +/- 26, p less than 0.02). The respiratory control ratio (RCR) was significantly lower in the transplanted than in the native hearts in both the FL and LL groups (p less than 0.05 and p less than 0.01 respectively). The comparison of the RCR in the two groups (FL vs LL) showed no significant difference for transplanted or native hearts. Electron microscopy of transplanted (rejected or not) and native hearts showed no morphological abnormality of the mitochondria. The lower VO2m of the allograft group indicates a disturbance in the mitochondrial respiratory pathway during acute rejection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in transthoracic electrical impedance during submaximal treadmill exercise in patients with ischemic heart disease--A preliminary report.

Twenty normal subjects and 32 patients with ischemic heart disease (IHD) were subjected to submaximal treadmill exercise. The mean transthoracic electrical impedance (TEI) was measured with a tetrapolar lead system and the changes were correlated to the extent of ST depression observed on an on-line digital computer. Six subjects of pre-excitation syndrome with "false" ST depression were also studied. The normal subjects did not show a significant change of TEI during exercise. The patients with IHD showed a steady and significant decrease in TEI, correlating with the extent of ST depression. Recovery was slow after the cessation of exercise. The subjects with false ST changes showed no decrease of TEI. The changes were more profound in subjects who developed anginal pain during the test. These findings are attributed to an increase in the thoracic blood volume and pulmonary extravascular water due to transient left ventricular dysfunction in angina.     

The potential clinical role of ultrasonic strain and strain rate imaging in diagnosing acute rejection after heart transplantation.

BACKGROUND: There has been a continued search for a more sensitive noninvasive technique for detecting sub-clinical acute rejection in heart transplant recipients. Ultrasonic deformation imaging (strain/strain rate) is sensitive in detecting sub-clinical abnormalities in regional systolic function and could potentially be sufficiently sensitive to detect changes in deformation induced by graft rejection. AIM: To assess the use of strain (S) and strain rate (SR) imaging as a noninvasive method for monitoring and diagnosing acute rejection in heart transplant recipients. METHODS AND RESULTS: A prospective preliminary study was carried out involving 31 consecutive heart transplant patients who underwent a total of 106 routine follow up endomyocardial biopsy with correlative cardiac ultrasound data. To assess regional longitudinal deformation, ultrasonic S and SR data were acquired from the intraventricular septum, left ventricular (LV) lateral and right ventricular free walls (RVFW). For radial deformation, data were obtained from the LV posterior wall (LVPW). According to the International Society of Heart and Lung Transplantation criteria, 88 biopsies (Group 1) had grade 0 or IA rejection, and 18 biopsies (Group 2) had > or =grade IB rejection. Longitudinal peak systolic S and SR were decreased (p<0.05) in Group 2, compared to Group 1 in the RVFW basal and apical segments and the basal and mid segments of the LV lateral wall. Radial peak systolic S and SR were significantly lower (p<0.001) in Group 2, compared to Group 1. CONCLUSIONS: S/SR imaging might be a good technique and an additional tool for detecting > or =IB grade of acute rejection. The myocardial deformation, as assessed by S/SR imaging could be of clinical value in monitoring and diagnosing acute rejection in heart transplant recipients and could improve patients' management by reducing the number of biopsies performed.     

Electrocardiographic diagnosis of acute graft rejection after heart transplantation]

In order to evaluate the diagnostic value of standard-ECG (ST-ECG) and precordial mapping-ECG with 63 unipolar leads (PM-ECG) for detection of acute cardiac allograft rejection, 15 patients (12 male, 3 female; age range 24-64 years) were studied. ST-ECG and PM-ECG were recorded along with 94 endomyocardial biopsies. Twenty-four acute rejections were detected histologically. Using the ST-ECG, a reduction of the QRS-amplitude-sum (lead I, II, III, V1 and V6) greater than or equal to 5% in comparison with the ECG obtained 1 week before was found to be the best diagnostic criterion (sensitivity 63%, specificity 74%, positive predictive value 48%, negative predictive value 85%). By analysing the PM-ECG a drop of the QRS-amplitude greater than or equal to 12% in greater than or equal to 14/63 precordial leads was determined to be the most reliable parameter (sensitivity 79%, specificity 71%, positive predictive value 49%, negative predictive value 91%). In contrast to the high sensitivity of PM-ECG, ST-ECG was less suitable for detection of acute rejection. However, taking into account the high negative predictive value of PM-ECG, acute rejection could be excluded with high probability, if the QRS-amplitudes of the PM-ECG remained stable. This may lead to a lower frequency of routinely performed endomyocardial biopsies.     

Diagnosis and treatment of acute rejection in the first case of human living-related small bowel transplantation with a long-term survival in China

AIM: To report the comprehensive diagnosis and treatment of acute rejection in the first case of living-related small bowel transplantation with a long-term survival in China. METHODS: A 18-year-old boy with short gut syndrome underwent living-related small bowel transplantation, with the graft taken from his father (44-year old). A segment of 150-cm distal small bowel was resected from the donor. The ileo-colic artery and vein from the donor were anastomosed to the infrarenal aorta and vena cava of the recipient respectively. The intestinal continuity was restored with an end-to-end anastomosis between the recipient jejunum and donor ileum, and the distal end was fistulized. FK506, MMF and prednisone were initially used for post-transplant immunosuppression. Endoscopic observation and mucosal biopsies of the graft were carried out through the terminal ileum enterostomy; serum was collected to detect the levels of IL-2R, IL-4, IL-6 and IL-8. The change of the graft secretion and absorption was observed. RESULTS: Acute rejection was diagnosed promptly and cured. The patient was in good health, 5 years after livingrelated small bowel transplantation. CONCLUSION: The correct diagnosis and treatment of acute rejection are the key to the long-term survival after living-related small bowel transplantation.     

Interleukin-17 Gene Expression and Serum Levels in Acute Rejected and non-Rejected Liver Transplant Patients

Background: Interleukin-17 (IL-17), as a potent proinflammatory cytokine, has a critical role in post liver transplant outcomes. However, there is not much information about the effects of IL-17 cytokine on acute liver rejection. Objective: To evaluate the role of IL-17 in post-liver transplant acute rejection. Methods: Ninety seven adult liver transplant patients who enrolled in this cross sectional study were divided into Non- Acute Rejected (Non-AR) and Acute Rejected (AR) patient groups. Three blood samples were collected from each patient in days 1, 4 and 7 post liver transplantation. The IL-17 mRNA levels were evaluated using an in-house real time PCR protocol. IL- 17 protein levels were also analyzed in Non-AR, AR and also control groups using ELISA method. Results: The IL-17 mRNA expression level continuously increased in AR patients in all days of follow-up post liver transplantation. IL-17 expression was, however, down regulated after day 4 post-transplant follow-up in Non-AR patients. Both IL-17 mRNA expression and protein levels were also significantly increased in AR patients compared with Non-AR ones. Conclusion: Based on these findings, significant increase of IL-17 mRNA and protein levels in AR patients highlights the important role of IL-17 in acute liver rejection.     

Effect of Fas -670 A/G Gene Polymorphism on Corneal Allograft Endothelial Rejection

Background: Human cornea expresses functional Fas-ligand capable of killing Fas+ activated lymphocytes. Fas expression is partly regulated by -670 A/G polymorphism in the promoter region of Fas gene. Objective: The aim of the present study is to determine the association between Fas-670A/G polymorphism and survival of corneal transplantation. Methods: In 276 graft recipients who mainly underwent penetrating keratoplasty because of keratoconus, bullous keratopathy and corneal opacity, Fas -670 A/G polymorphism was determined by allele specific oligonucleotide polymerase chain reaction (ASO-PCR) techniques. Results: There was no statistically significant relationship between Fas -670 A/G polymorphism and rejection episode (p=0.35). Moreover, the relationship between this polymorphism and rejection episode outcome (transplant recovery vs failure) was not statistically significant (p=0.13). Conclusion: The results of the present study show no significant correlation between corneal graft rejection, rejection recovery and Fas -670A/G gene polymorphism.     

穿孔素及颗粒酶B在肝移植排斥反应中的表达及意义

目的检测穿孔素和颗粒酶B在肝移植术后排斥反应中的表达情况，以评价其作为肝移植术后排斥反应的早期诊断指标价值。方法收集35个肝移植术后肝穿刺标本，应用免疫组织化学方法检测穿孔素和颗粒酶B表达，并与病理组织学结果相比较，研究其表达与急性排斥反应的关系。结果在35个标本中，19个经病理组织学诊断为排斥反应，其中急性排斥17例次，慢性排斥2例次。其中穿孔素和颗粒酶B在排斥反应者中的表达阳性率分别为100％(19／19)和94．7％(18／19)。而在未发生排斥反应者中，其表达阳性率分别为25．0％(4／16)和12．5％(2／16)。穿孔素及颗粒酶B多呈同步表达，仅3个标本为仅有穿孔素表达而无颗粒酶B表达，未观察到仅有颗粒酶B表达而无穿孔素表达。穿孔素和颗粒酶B的阳性表达与移植肝急性排斥反应的发生密切相关。结论穿孔素和颗粒酶B参与了肝移植后排斥反应的发生，其表达可作为术后急性排斥反应的辅助诊断指标。     

Echocardiographic diagnosis of acute graft rejection in heart transplant patients under cyclosporin therapy

Though endomyocardial biopsy has remained the gold standard for diagnosing acute cardiac rejection (AR), this invasive method does not provide adequate means for close monitoring of the rejection process. In order to assess the usefulness of M-Mode- and two-dimensional (2D) echocardiography for the noninvasive diagnosis of AR in heart transplant recipients on cyclosporin, 45 patients (mean age 40.6 +/- 8.8 years, 19.9 +/- 14.4 months postoperatively) were evaluated prospectively. Mean observation time was 9.1 +/- 4.8 months. Echocardiographic examination techniques were strictly standardized; besides measurements of left (LV) and right ventricular (RV) diastolic wall thickness and of the isovolumic relaxation time, computerized frame-by-frame-analysis was applied to LV short axis cross sections for the determination of diastolic cavity cross-sectional area and extent and mean velocity of systolic and diastolic area change. To account for technical and biological variability, 95%-confidence limits were calculated for each parameter from two rejection-free examinations, allowing identification of significant changes during AR. In this study, 36 biopsy-proven AR occurred in 19 patients. Compared to control values, mean heart rate increased from 86.2 +/- 10.2 to 94.6 +/- 15.1 b/min (p less than 0.05), diastolic septal + posterior wall thickness from 21.2 +/- 4.1 to 24.9 +/- 6.2 mm (p less than 0.001) and RV free wall thickness from 6.3 +/- 1.1 to 8.9 +/- 1.8 mm (p less than 0.001). Isovolumic relaxation time decreased from 73.2 +/- 14.4 to 54.8 +/- 16.6 ms (p less than 0.001), diastolic cross-sectional area from 12.8 +/- 2.0 to 11.1 +/- 2.2 cm2 (p less than 0.05), relative area change from 65.8 +/- 9.8 to 49.1 +/- 14.4% (p less than 0.001) and systolic and diastolic area change velocities from 28.1 +/- 7.8 and 41.8 +/- 8.5 cm2/s to 18.9 +/- 5.6 and 28.6 +/- 9.2 cm2/s, respectively (p less than 0.001). Though significant changes occurred during AR, most measurements remained within the normal range. Thus, in individual patients, AR could only be suspected in comparison to the control measurements. None of the examined parameters allowed to establish the diagnosis of AR in all instances. However, when the measurements of all parameters were considered together, 35 of the 36 AR diagnosed by biopsy could also be identified by echocardiography, including all requiring intensified immunosuppressive therapy. Mild AR was not always detected, and the differential diagnosis between LV hypertrophy and AR required an endomyocardial biopsy in some instances.(ABSTRACT TRUNCATED AT 400 WORDS)     

Plasmapheresis in the treatment of acute vascular rejection: an experience on a dialysis unit

Despite numerous the advances made in transplantation, acute rejection remains a major complication. Recent studies have shown that the use of plasmapheresis in the treatment of acute vascular rejection improves the chances of graft survival. In 1997 the plasmapheresis was transferred to the management of the renal unit, because we could offer a 24‐hour service for all acute cases in our hospital. The number of cases has steadily increased, incorporating not only plasmapheresis, but also stemcellpheresis and red blood cell exchanges. Since July 2003, we have started using plasmapheresis in the treatment of acute vascular rejection in renal transplants. When a biopsy shows acute vascular rejection (A.V.R), combined with a decreased urine production, the patient commences therapy. Treatment consists of consecutive sessions, alternating between two sessions using saline/albumin followed by one session using fresh frozen plasma. Depending on the lymphocyte count, therapy is carried out in conjunction with a course of Antithymocyte globulin (A.T.G.) between July 2003 and October 2004, 124 transplants were carried out, 15 suffered from acute rejection. Six were diagnosed with A.V.R, of these six; five were successfully treated with plasmapheresis and A.T.G. One patient only needed plasmapheresis to ensure a reversal of acute vascular rejection. We encountered no problem with the technique itself and although plasmapheresis seems to improve the outcome of graft survival, we need to ask ourselves, as demand increases: “Do we have the capacity to treat these patients on our unit in the future and is it our domain?”     

小鼠心脏移植后穿孔素及颗粒酶B表达水平与急性排斥反应的关系

目的:研究穿孔素和颗粒酶B蛋白在心脏移植后表达水平变化与心脏移植急性排斥反应的关系.方法:采用小鼠腹部心脏移植模型,分为移植排斥组、实验处理组和同系移植组,每组20对.观察移植物存活时间、供心病理改变.采用Western blot法检测受鼠脾脏淋巴细胞穿孔素及颗粒酶B蛋白表达水平,免疫荧光方法观察心脏移植物内穿孔素及颗粒酶B的表达情况.结果:移植排斥组及实验处理组移植物平均存活时间分别为7.8±0.77 d、14.80±1.01d,同系移植组移植物存活均超过28 d,三组差异有显著性.移植排斥组与实验组及同系移植组相比较,移植物内心肌细胞变性坏死严重并有大量炎性细胞浸润.移植术后7 d,移植排斥组与实验处理组和同系移植组相比,受鼠脾脏淋巴细胞穿孔素蛋白表达分别增加3.02倍、4.13倍.颗粒酶B蛋白表达分别增加3.44倍、2.50倍,差异有显著性.与另外两组相比,移植排斥组心脏移植物冠状动脉分支内充填大量穿孔素与颗粒酶B阳性细胞,组织间隙内也有较多双阳性细胞浸润.结论:穿孔素与颗粒酶B蛋白表达增加与急性排斥反应相关,可作为急性排斥反应的早期诊断指标.