Tacrolimus Exposure and Evolution of Renal Allograft Histology in the First Year After Transplantation

Tacrolimus has a narrow therapeutic window and is characterized by a large inter-individual variability in bioavailability. The impact of tacrolimus exposure on subclinical evolution of graft histology has not been studied in renal recipients. This analysis included 239 protocol biopsies (obtained at implantation, 3 and 12 months) of 120 consecutive kidney recipients treated with tacrolimus, mycophenolate mofetil (MMF) and corticosteroids. Biopsies were scored according to the Banff 2001 criteria and a chronicity score was calculated. Prospective pharmacokinetic data were included in the analysis (5544 tacrolimus predose blood concentrations and tacrolimus AUC(0-12) at 3 and 12 months). Higher donor age and higher number of human leukocyte antigen-DR (HLA-DR) mismatches were independent predictors of subclinical acute rejection at 3 months, present in 8.7% of patients. The number of HLA-DR mismatches was independently associated with biopsy-proven clinical acute rejection. Biopsy-proven acute rejection episodes and low mean tacrolimus exposure were independently associated with higher increase in chronicity scores between 3 and 12 months after transplantation. This observational study suggests that rejection phenomena and immune-mediated mechanisms remain important in the early progression of chronic allograft pathology. Tacrolimus doses or systemic exposure were not associated with lesions of calcineurin inhibitor nephrotoxicity, suggesting that other factors determine susceptibility to tacrolimus nephrotoxicity.     

亚临床甲状腺功能减退症患者TSH与肾上腺皮质功能的关系

目的分析亚临床甲状腺功能减退症患者促甲状腺激素(TSH)与肾上腺皮质功能的关系。 方法选取150例亚临床甲状腺功能减退症患者为研究组,甲状腺功能正常的健康人群150例为对照组。比较两组TSH、游离三碘甲腺原氨酸(FT3)、游离甲状腺素(FT4)、皮质醇(CORT)和促肾上腺皮质激素(ACTH)水平。采用Pearson法分析亚临床甲状腺功能减退症患者TSH水平与ACTH、CORT水平的相关性。 结果与对照组比较,研究组患者TSH、ACTH水平升高,CORT水平降低(P＜0.05)。Pearson分析结果显示,亚临床甲状腺功能减退症患者TSH水平与ACTH水平呈正相关(P＜0.05),与CORT水平呈负相关(P＜0.05)。 结论亚临床甲状腺功能减退症患者血清TSH水平与肾上腺皮质功能指标ACTH、CORT水平存在相关性。     

P300等诱发电位对亚临床肝性脑病早期诊断的意义

目的:观察事件相关电位P_(300)、体感诱发电位、视觉诱发电位和脑干听觉诱发电位在亚临床肝性脑病诊断中的意义。方法:50例亚临床肝性脑病患者进行了心理测验,并做了头颅CT和视觉诱发电位、体感诱发电位、脑干听觉诱发电位和事件相关电位检查,30例正常人做为对照组。结果:亚临床肝性脑病的心理测验,韦氏法智力低下率为76％,视觉诱发电位异常率为13％,脑干听觉诱发电位异常率为20％,体感诱发电位异常率为40％,事件相关电位异常率为71％,正常对照组四种诱发电位的正常率是100％。头颅CT结果与亚临床肝性脑病无关。结论:视觉诱发电位、体感诱发电位、脑干听觉诱发电位和事件相关电位在亚临床肝性脑病中是异常的。事件相关电位更为敏感,对亚临床肝性脑病的早期诊断有重要意义。     

Does subclinical rejection contribute to chronic rejection in renal transplant patients?

Renal allograft biopsies have traditionally been performed in the setting of acute graft dysfunction. However, several groups have performed graft biopsies at times of stable graft function, and more recently, after treatment of rejection episodes. Surprisingly, unequivocal histologic criteria for acute rejection have been demonstrated in a high proportion of these protocol biopsies. The Winnipeg Transplant Group has documented the high prevalence of clinically silent inflammatory infiltrates in early protocol biopsies, and demonstrated their inflammatory and cytotoxic potential by immunohistochemical and molecular biological techniques. Furthermore, in a randomized trial, our group has demonstrated that subclinical rejection, if untreated, is associated with the development of early chronic pathology and late graft dysfunction. In this overview, we will summarize the early data on subclinical allograft inflammation, present the experience of the Winnipeg Transplant Group, and discuss the possible implications of subclinical rejection on the development of chronic rejection.     

古拉定在肝硬化亚临床肝性脑病治疗中的临床意义

目的　探讨古拉定 (GLT)在肝硬化亚临床性肝性脑病 (SHE)治疗中的临床意义。方法　以古拉定联合乳果糖治疗 4 7例SHE ,在 1mon治疗结束后随访 6mon ,并以单用乳果糖治疗的 5 0例SHE作对照 ,观察智力测验好转情况及肝功能改变情况。结果　数字连接试验 (NCT)及数字符合试验 (DST)在治疗结束及随访 6mon时的好转率分别为 69 0 %、5 2 6%和 4 7 6%、5 0 % ,而对照则分别为 4 0 8%、4 5 0 %和 17 4 % ,除DST治疗 1mon时两组差异无显著性外 ,两组其余各项比较差异均有显著性 (P <0 0 5或P <0 0 1) ;治疗组肝功能Child Pugh计分在治疗前为 8 92± 1 16,治疗 1mon时降为 7 73± 1 3 1(P <0 0 1) ,随访 6mon时为 8 0 2± 1 17(P <0 0 5 ) ,而对照组在治疗前为 8 65± 2 4 1,1mon时为 7 86± 1 4 6(P <0 0 5 ) ,至 6mon时为 8 4 4± 1 87,与治疗前差异无显著性。结论　古拉定能提高乳果糖对肝硬化SHE治疗的近期疗效及远期疗效 ,机制可能是通过改善肝功能状态而起作用     

关于亚健康状态的躯体、心理和社会因素的调查研究

目的：阐明亚健康的躯体、心理、社会多方面的影响。方法：采用问卷评定量表调查表，向每个对象发放问卷评定量表，并由本人自己填写。结果：亚健康患者心理社会应激和宽容者与症状的发生有关，其中心理社会应激对症状的发生影响最大，宽容者自己对付不良身体状态的能力较高，不易发生身体症状。结论：使用躯体、生理、社会因素的测定来掌握“亚健康状态”，寻找发病原因，对患者进行教育非常必要。     

High Prevalence of Subclinical Atherosclerosis by Carotid Ultrasound among Mexican Americans: Discordance with 10‐Year Risk Assessment using the Framingham Risk Score

Background: Framingham risk scores (FRS) were validated in a mostly Caucasian population. Evaluation of subclinical atherosclerosis by carotid ultrasound may improve ascertainment of risk in nonwhite populations. This study aimed to evaluate carotid intima‐media thickness (cIMT) and carotid plaquing among Mexican Americans, and to correlate these markers with coronary risk factors and the FRS. Methods/Results: Participants (n = 141) were drawn from the Cameron County Hispanic Cohort. Carotid artery ultrasound was performed and cIMT measured. Carotid plaque was defined as areas of thickening >50% of the thickness of the surrounding walls. Mean age was 53.1 ± 11.7 years (73.8% female). Most were overweight or obese (88.7%) and more than half (53.2%) had the metabolic syndrome. One third (34.8%) had abnormal carotid ultrasound findings (either cIMT ≥75th percentile for gender and age or presence of plaque). Among those with abnormal carotid ultrasound, the majority were classified as being at low 10‐year risk for cardiovascular events. Carotid ultrasound reclassified nearly a third of the cohort as being at high risk. This discordance between 10‐year FRS and carotid ultrasound was noted whether risk was assessed for hard coronary events or global risk. Concordance between FRS and carotid ultrasound findings was best when long‐term (30‐year) risk was assessed and no subject with an abnormal carotid ultrasound was categorized as low risk by the 30‐year FRS algorithm. Conclusions: Integration of carotid ultrasound findings to coronary risk assessments and use of longer term prediction models may provide better risk assessment in this minority population, with earlier initiation of appropriate therapies.