Chemonucleolysis: a note of caution

Following the approval in 1982 by the Federal Food and Drug Administration of chymopapain for public use by the medical profession in the treatment of ruptured lumbar intervertebral disk disease, chemonucleolysis has become widespread in the United States; a considerable experience has been obtained in the past 3 years, allowing for an appropriate examination of the original claims for the procedure. Chemonucleolysis is not as efficacious as surgery for simple ruptured lumbar intervertebral disk disease. Whereas the complication rates of chemonucleolysis are probably no greater than that for surgery, the incidence of unpreventable anaphylaxis and other untoward reactions makes it certainly no more safe. There is no biological basis for the belief that chemonucleolysis will result in a shorter convalescence than surgery, and it appears that chemonucleolysis has significantly increased the cost of invasive treatment of patients with ruptured lumbar intervertebral disk disease.     

多药耐药基因表达与肾移植急性排斥机制的初步探讨

目的：研究多药耐药基因（MDR1）与肾移植受者急性排斥的关系。方法：用定量RT-PCR技术分别检测14全我急性排斥受者和28例肾功能稳定受者MDR1表达水平，并与36例尿毒症患者比较；14例健康人作为对照组。结果：MDR1阳性表达率急性排斥受者为85.7%。肾功能稳定受者为71.4%。尿毒症患者为44.4%，前二者表达率均高于尿毒症患者，而且急性排斥受者MDR1含量大于肾功能稳定的受者。结论：在肾移植受者中表达增加可能是肾移植受者获得对CsA耐受从而在CsA治疗浓度下发生排斥的机制之一。     

Combined analysis of cytokine gene polymorphism and the level of expression with allograft function in kidney transplant recipients

Cytokines are important factors determining the outcome of transplantation since host ability in cytokine production may be affected by cytokine gene polymorphisms. The aim of the present study was to investigate the effect of IL-17, IL-23R and IL-21 gene polymorphisms in the outcome of kidney transplantation.A total of 250 kidney transplant recipients were included in this study. Overall 70 recipients (28%) experienced an acute rejection. IL-17 197 A/G, IL-21 + 1472 G/T, IL-21 5250 C/T, and IL-23R C/T gene polymorphisms were evaluated by PCR-RFLP or ARMS-PCR methods. The serum levels of IL-17 and IL-21 were also checked by ELISA.IL-17 GG carriers and G allele were significantly more frequent in patients with acute rejection as compared to patients without any sign of rejection (P = 0.045 and P = 0.032, respectively). In addition after gender classification, IL-23R AA carriers and A allele were significantly more frequent in male patients who experienced an acute rejection as compared to non-rejected patients (P = 0.03, P = 0.011, respectively). The IL-17 serum levels have also shown significant differences between rejected and non-rejected groups (24.37 ± 32.94 for AR and 8.6 ± 9.9 for non-AR groups, respectively; P = 0.035).The mentioned results indicate that IL-17GG genotype, G allele and its serum level have predictive values for acute rejection. GG genotype and G allele of IL-17 is a genetic risk factor for development of acute rejection. Also, AA genotype and A allele of IL-23R is a sex dependent genetic risk factor for the development of acute rejection, but this subject needs to be studied in a different population.     

Oxygenation of cardioplegic solutions: a note of caution

The merits of oxygenated crystalloid cardioplegic solutions have been well established in experimental animals. The positive effects of oxygenation of Plasmalyte B (Sabax Ltd) and St. Thomas Hospital solution (Plegisol) were achieved by gassing with 95% O2/5% CO2 and 100% O2, respectively. In view of the marked pH differences induced by these gas mixtures, we evaluated the effect of mode of oxygenation on myocardial recovery during reperfusion after hypothermic cardioplegic arrest. Oxygenation with 100% O2 of Plasmalyte B containing high K+ levels caused marked deterioration in myocardial recovery, whereas the mode of oxygenation did not affect recovery after arrest with St. Thomas Hospital solution. Because the major differences between these solutions reside in their respective K+, Mg2+, and HCO3- contents, the effects of variations in the levels of these ions were investigated. The results showed that oxygenation with 100% O2 was deleterious only in the presence of high K+ (29 mmol/L), low Mg2+ (3 mmol/L), and high NaHCO3 (28 mmol/L) levels. The marked decline in mechanical recovery during reperfusion was associated with significant changes in myocardial adenosine triphosphate and intracellular Ca2+ levels. Although an explanation for these findings is not readily available, it is suggested that complex ionic interactions and possibly oxygen free radical generation may lead to intracellular Ca2+ overload, depression in mitochondrial adenosine triphosphate generation, and, hence, deterioration in mechanical recovery.     

Life satisfaction and adverse effects in renal transplant recipients: a longitudinal analysis

INTRODUCTION: Previous cross-sectional analyses have identified significant associations between quality of life (QOL), comorbidities and adverse effects in renal transplant recipients. This report examines the longitudinal relationship between adverse effects and QOL, with particular attention to the relative impact of adverse effects associated with immunosuppression. METHODS: The Transplant Learning Center (TLC) is a program designed to improve QOL and preserve graft function in transplant recipients. Self-selected enrollees filled out questionnaires at roughly 3-month intervals. Each questionnaire included QOL scales developed for the program. Repeated measures multiple regression analysis was used to examine the relationship between the QOL scales, comorbidities, adverse effects, adjusting for other factors. RESULTS: A total of 4247 TLC enrollees were included in the analysis, with a mean time since transplant of 5.1 yr. Comorbidities and adverse effects were common, with high blood pressure reported by 87% of respondents and unusual hair growth reported by 69.6%. In bivariate analysis, emotional/psychological problems and headaches had the largest impact on QOL. In multivariate analysis, emotional/psychological problems decreased sexual interest or ability, and headache had the largest adverse QOL effect. CONCLUSIONS: We have identified QOL issues that have been previously underemphasized in transplant recipients. These findings open new areas of research to further explore and define these issues. They provide new opportunities for interventions to address factors adversely impacting QOL and to develop strategies to improve QOL in these patients. Clinicians should actively solicit information about adverse effects of medications, particularly information about sexual and relationship issues, when evaluating renal recipients. These issues should be taken into account when making therapeutic decisions.     

Adenotonsillar enlargement in pediatric organ transplant recipients: a cross-sectional analysis.

OBJECTIVE: Our goal was to statistically correlate adenotonsillar hypertrophy (ATH) in the pediatric posttransplant population with potential risk factors and to monitor the progression of ATH over time. STUDY DESIGN AND SETTING: Participants were evaluated for ATH through a standardized 65-point questionnaire and an 8-point physical examination. They were also evaluated for current age, age at time of transplantation, type of organ transplant, gender, tacrolimus use, history of transplant rejection, Epstein-Barr virus (EBV) serology, and cytomegalovirus (CMV) serology. We evaluated 243 pediatric solid organ transplant recipients, with 116 patients undergoing repeat evaluation. RESULTS: A statistically significant negative correlation was noted between age at time of transplantation and both questionnaire scores (P = 0.0075) and examination scores (P = 0.013). A significant negative correlation was also seen between age at time of evaluation and questionnaire score (P = 0.028) but not examination score (P = 0.49). Recipient EBV seronegativity significantly increased questionnaire score (P = 0.05). Liver transplant recipients also had a significantly higher questionnaire score than did kidney transplant recipients (P = 0.0048). Gender, CMV recipient status, and tacrolimus (immunosuppressant) use did not significantly impact questionnaire or examination scores. Repeat evaluation of 116 patients after a 2- to 9-month interval did not demonstrate any significant increases in questionnaire scores. A statistically significant drop in examination scores was noted (P = 0.003). Conclusions and Significance: These findings support previous reports in the literature that correlate EBV seronegativity, younger age at transplant, and liver versus kidney transplantation with increased incidence of PTLD.     

Nosocomial infection in kidney transplant recipients: a retrospective analysis of a single-center experience

Posttransplant bacterial infections are important because of their influence on patient and graft outcomes. Therefore, prevention of infection as well as prompt diagnosis and appropriate treatment are crucial. In this retrospective analysis, we reviewed all posttransplant bacterial infections occurring during the admission of kidney transplant patients from January 2000 to May 2004. Of our patients, 25% had at least one episode of infection. Patients with immunosuppression based on an mTOR inhibitor showed the highest rate of wound infections compared to those receiving a calcineurin inhibitor (odds ratio 5.6, P < .001). Patients with renal failure caused by a urologic disease revealed a increased risk of a urinary tract infections (odds ratio 5.9, P < .001). Although infection complications are an important cause of morbidity in renal transplantation, the extensive use of antibiotics should be avoided in favor of a strict policy for infection prevention and control.     

Immune response gene polymorphisms in renal transplant recipients

BACKGROUND: T-cell activation and regulation are under genetic control and vary between individuals. However, the influence of functional immune response gene polymorphisms on transplant outcomes remains controversial. METHODS: A case-control design compared 100 white renal transplant recipients with or without acute graft rejection during the first year posttransplant and 50 normal controls. The polymorphic frequencies of the T-cell signaling genes CD45, CD40L and CTLA-4, and the cytokine genes TNF-alpha, IFN-gamma, IL-10 and TGF-beta1 were studied. The primary analysis examined rejection risk, and subsidiary analyses graft failure and patient death. RESULTS: Multivariate analysis showed no significant association between acute rejection and single nucleotide polymorphisms in CTLA-4, TGF-beta1, IL-10 or TNF-alpha genes or dinucleotide repeat polymorphisms in IFN-gamma and CD40L genes. Allele CD40L-147 was associated with reduced graft failure (P=0.004), and TGFb-25pro with increased graft failure (P=0.0007), although the latter showed a bidirectional dose effect. There was no significant association between patient death and any polymorphisms in the genes examined. The variant (G) allele of the CD45 gene was not detected in the study population. Minor differences in carriage rates observed by univariate analysis did not predict graft or patient outcome in multivariate analysis. CONCLUSION: The primary analysis demonstrated no significant association between the immune response gene polymorphisms examined and acute renal graft rejection in Caucasian patients receiving triple immunosuppression. Subsidiary analyses suggesting an influence of CD40L and TGFbeta1 genes on graft survival require independent confirmation.     

肾移植受者新发高甘油三酯血症的危险因素：单中心分析

目的  探讨肾移植受者新发高甘油三酯血症（HTG）的危险因素。 方法  回顾性分析149例肾移植受者的临床资料,根据术后血清甘油三酯（TG）水平,分为无HTG组（TG≤1.7 mmol/L,60例）与新发HTG组（TG>1.7 mmol/L,89例）。比较两组受者的一般资料,采用广义估计方程（GEE）分析肾移植受者发生HTG的危险因素,并应用多个回归方程验证。 结果  两组受者一般资料差异均无统计学意义（均为P>0.05）。多因素分析结果显示,与低浓度Tac组受者相比,中浓度Tac组和高浓度Tac组的HTG发生率升高[中浓度Tac组比值比（OR）3.11,95%可信区间（CI）1.22～7.93,P=0.018;高浓度Tac组OR 5.11,95%CI 1.31～19.98,P=0.019]。与A型血受者相比,O型血受者新发HTG的风险增加（OR 2.77,95%CI 1.14～6.71,P=0.024）。随着术前球蛋白水平升高,受者新发HTG的风险降低（OR 0.93,95%CI 0.87～0.99,P=0.043）。术后3个月时,新发HTG组Tac血药浓度高于无HTG组,差异有统计学意义（P<0.05）。多个回归方程验证了O型血肾移植受者较A型血受者新发HTG的风险增加,中浓度Tac组和高浓度Tac组肾移植受者较低浓度Tac组新发HTG的风险增加（均为P<0.05）。 结论  O型血肾移植受者更易发生HTG,加强血脂的术后监测和控制十分重要。Tac血药浓度对肾移植受者术后新发HTG可能存在一定影响,维持适宜血药浓度可能有利于降低HTG发生率。