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31.
Y. Le Meur M. Büchler A. Thierry S. Caillard F. Villemain S. Lavaud I. Etienne P.-F. Westeel B. H. de Ligny L. Rostaing E. Thervet J. C. Szelag J.-P. Rérolle A. Rousseau G. Touchard P. Marquet 《American journal of transplantation》2007,7(11):2496-2503
Efficacy and safety of mycophenolate mofetil (MMF) may be optimized with individualized doses based on therapeutic monitoring of its active metabolite, mycophenolic acid (MPA). In this 12-month study, 137 renal allograft recipients from 11 French centers receiving basiliximab, cyclosporine A, MMF and corticosteroids were randomized to receive either concentration-controlled doses or fixed-dose MMF. A novel Bayesian estimator of MPA AUC based on three-point sampling was used to individualize doses on posttransplant days 7 and 14 and months 1, 3 and 6. The primary endpoint was treatment failure (death, graft loss, acute rejection and MMF discontinuation). Data from 65 patients/group were analyzed. At month 12, the concentration-controlled group had fewer treatment failures (p = 0.03) and acute rejection episodes (p = 0.01) with no differences in adverse event frequency. The MMF dose was higher in the concentration-controlled group at day 14 (p < 0.0001), month 1 (p < 0.0001) and month 3 (p < 0.01), as were median AUCs on day 14 (33.7 vs. 27.1 mg*h/L; p = 0.0001) and at month 1 (45.0 vs. 30.9 mg*h/L; p < 0.0001). Therapeutic MPA monitoring using a limited sampling strategy can reduce the risk of treatment failure and acute rejection in renal allograft recipients 12 months posttransplant with no increase in adverse events. 相似文献
32.
M. Diez L. Favaloro A. Bertolotti J. M. Burgos C. Vigliano M. P. Lastra M. J. Levin A. Arnedo C. Nagel A. G. Schijman R. R. Favaloro 《American journal of transplantation》2007,7(6):1633-1640
Heart transplantation (HTx) is a useful therapy for end‐stage Chaga? cardiomyopathy; however, Chagas reactivation remains a mayor complication. Parasitological methods offer poor diagnostic sensitivity, and use of more sensitive tools such as the Polymerase chain reaction (PCR) is usually necessary. In the present study, reactivation incidence and PCR usefulness for early reactivation diagnosis, as well as for treatment response evaluation during follow‐up, were analyzed using Strout parasite detection test, in 10 of 222 consecutive HTx patients suffering Chagas cardiomyopathy. PCR strategies targeted to minicircle sequences (kDNA, detection limit 1 parasite/ 10 mL blood) and miniexon genes (SL‐DNA, 200 parasite/10 mL) were performed to compare parasite burdens between samples. No patients received prophylactic antiprotozoal therapy (benznidazole). Five patients (50%) exhibited clinical reactivation within a mean period of 71.6 days; positive Strout results were observed in most cases presenting clinical manifestations. kDNA‐PCR was positive 38–85 days before reactivation, whereas SLDNA‐PCR became positive only 7–21 days later, revealing post‐HTx parasitic load enhancement present prior to clinical reactivation development. Reactivations were successfully treated with benznidazole and generated negative PCR results. Results observed in this study indicate the value of PCR testing for an early diagnosis of Chagas reactivation as well as for monitoring treatment efficacy. 相似文献
33.
The greatest benefit of immunosuppression minimization for children may lie in improving patient morbidity, by the elimination of the inherent side effects of steroid and calcineurin inhibitors (CNI). The newer generation of powerful induction and maintenance immunosuppressants offers an option for selected immunosuppression minimization strategies, some of which have been shown to also reduce graft morbidity. Steroid minimization and avoidance in single-center uncontrolled trials have shown early promise and the availability of data from an ongoing randomized, prospective, controlled trial of steroid avoidance in children will provide necessary data to support a practice change for steroid elimination in children. Calcineurin inhibitor minimization and addition of mycophenolate mofetil (MMF) or sirolimus have shown variable improvements in renal function, though suboptimal efficacy and safety with the currently proposed regimes have limited their application. Randomized, prospective studies of steroid and calcineurin inhibitor minimization and/or avoidance are warranted to clearly confirm the short and long-term safety and efficacy of alternative immunosuppression combinations. Linked pharmacokinetic and mechanistic studies within these trials will allow for optimizing drug dosing and monitoring. This article reviews published experience to date with steroid and calcineurin minimization in pediatric renal transplantation and discusses the risks and benefits of these approaches. 相似文献
34.
R. A. Wolfe F. B. LaPorte A. M. Rodgers E. C. Roys G. Fant A. B. Leichtman 《American journal of transplantation》2007,7(S1):1404-1411
Turndowns of offers of deceased donor kidneys for transplantation can contribute to inefficiencies in the organ distribution system and inequality in access to donated organs. Match run data were obtained for 4967 'good' kidneys placed and transplanted in 2005 after fewer than 50 offers. These kidneys were not recovered from donation after cardiac death or expanded criteria donors, or from donors with a history of substance abuse. On average, these good kidneys were not accepted until after seven offers to candidates and after offers to 2.4 programs. Models for the likelihood of acceptance found several donor and candidate characteristics to be significantly related to acceptance rates (p < 0.05). After accounting for these variables, there remained 2- to 3-fold differences among transplant programs in acceptance rates. These models could be used to identify kidney transplant centers with exceptional acceptance practices. Several strategies might be employed to increase acceptance rates for good organs. 相似文献
35.
同种异体骨支撑架微创治疗股骨头坏死的临床研究 总被引:1,自引:0,他引:1
目的应用改良髓芯减压术结合同种异体骨支撑架加自体骨和脱钙骨基质(decalcified bone matrix,DBM)治疗早期股骨头坏死,探索早期股骨头坏死的微创治疗方法。方法2004年1月~2005年4月,23例24个髋关节采用经大转子下通过股骨颈钻隧道至股骨头骨坏死区,将装有自体松质骨和DBM的同种异体骨支撑架经隧道拧入骨坏死区直至软骨下骨约5mm处,隧道远端用自体髂骨填塞。观察手术前后Harris评分变化、x线影像学表现及是否需进一步治疗。结果本组所有患者均获得随访,平均随访19(12—27)个月,以最后一次随访资料作为最终评价依据。Harris评分,术前优良率为43.5%(10/23)。术后优良率为91.3%(21/23)。22侧髋关节影像学表现保持稳定,无明显并发症发生。结论同种异体骨支撑架植入结合自体松质骨和DBM治疗成人股骨头坏死,增加了股骨头负重区软骨下骨的机械支撑,成骨作用强,有利于股骨头坏死的修复与重建,同时,不破坏患者股骨头本身的血液供应,创伤小,操作简单,值得临床推广使用。 相似文献
36.
Javairiah Fatima Scott G. Houghton Michael G. Sarr 《Journal of gastrointestinal surgery》2007,11(8):1052-1056
Small bowel transplantation (SBT) is associated with poorly understood enteric dysfunction. The study of SBT in mice is hindered
by the technical difficulty of orthotopic SBT in the mouse. Our aim was to develop an easy preparation of extrinsic denervation
of the entire jejunoileum in mice as a model of orthotopic SBT. All neurolymphatic tissues accompanying the superior mesenteric
artery (SMA) and vein (SMV) were ligated just distal to the middle colic vessels. The SMA and SMV were then stripped of investing
adventitia, and the mesentery to jejunum and colon were transected radially. Jejunum and colon were not transected and reanastomosed.
To confirm extrinsic denervation 1, 3, and 6 months later, segments of small bowel were stained for protein gene product 9.5
(PGP9.5) and tyrosine hydroxylase (TH). Tyrosine hydroxylase immunoreactive intensity was then quantified using a semiquantitative
analysis. Immunohistochemical fluorescence showed persistence of PGP9.5 immunoreactivity confirming enteric nerves in jejunoileum;
however, there was no TH immunoreactivity in jejunoileum in denervated mice despite the expected preservation of TH immunoreactivity
in the still-innervated duodenum at 1 month. At 3 months, sparse immunoreactivity for TH was present, and by 6 months, reinnervation
of TH-containing nerves appeared similar to controls. Quantification of intensity at each time-point further confirmed this
trend. This technique in the mouse accomplishes a complete extrinsic denervation of jejunoileum early postoperatively (1 and
3 months); reinnervation occurs by 6 months. This is an easily learned murine model of orthotopic SBT.
Presented at the American Gastroenterological Association during Digestive Disease Week in Los Angeles, CA, as a poster presentation
on May 23 2006. Abstract published in GastroenterologyE 2006; 130:A604. 相似文献
37.
Neurologic complications are common after transplantation and affect 30-60% of transplant recipients. The etiology of most of the posttransplant neurologic disorders is related to the opportunistic infections, both systemic and involving central nervous system (CNS), toxicity of immunosuppressive medications, and the metabolic insult created by the underlying primary disease and the transplant procedure. Neuroimaging studies are one of the key tools in the evaluation and enable early diagnosis of neurologic complications in transplant patients, especially posterior reversible leukoencephalopathy syndrome, central pontine myelinolysis, intracerebral hemorrhage, and fungal and bacterial abscesses. Magnetic resonance imaging (MRI) is the preferred technique, but each of the available neuroimaging techniques offers a unique insight into the pathophysiologic mechanisms underlying neurologic complications of transplantation. The role of neuroimaging in this population includes early detection of calcineurin inhibitor neurotoxicity, opportunistic infections, neoplasia, metabolic disorders, or cerebrovascular diseases. In addition, we can monitor longitudinal progression of disease and treatment response. 相似文献
38.
G. S. Sayuk T. L. Leet M. A. Schnitzler P. H. Hayashi 《American journal of transplantation》2007,7(1):151-160
Deceased donor factors associated with poor graft outcome are well known, but how often these factors lead to livers left untransplanted is poorly defined. A nested, case-control study was conducted using the United Network for Organ Sharing (UNOS) database from 1987 to 2005. Only those donating >/=1 solid organ were included. Primary outcome was livers not transplanted (LNT, cases) versus transplanted (LT, controls). Primary variables for multivariate analysis were donor age and obesity. Covariates included donation after cardiac death (DCD), cerebral vascular accident death, viral serologies, cancer, ALT and bilirubin. There were 23 373 (26%) LNT's from 91 362 donors who donated at least one organ. Percent LNT fell over time (1987-1990: 48%; 1991-1995: 29%; 1996-2000: 21%; 2000-2005: 16%; p < 0.01). Increased age (odds ratio: 4.2, 95% confidence interval 3.6-4.9, p < 0.01) and obesity (2.1, 1.9-2.3, p < 0.01) were significantly associated with LNT across all time periods. Other significant factors included DCD and elevated ALT. For 2001-2005, population attributable risk indicate that age >40, abnormal ALT and obesity account for 32.6%, 25.3% and 9.2% of untransplanted livers, respectively. Use of expanded criteria livers has pushed LNT lower in spite of an aging and heavier donor population. Nevertheless, age and obesity still account for a significant portion of untransplanted livers. 相似文献
39.
Michael Robson Isabelle Côte Ian Abbs Geoffrey Koffman David Goldsmith 《American journal of transplantation》2003,3(3):324-327
Thrombotic microangiopathy is a rare but important finding in the context of organ transplantation. Acute renal insufficiency in the setting of hemolysis and thrombocytopenia, a triad that constitutes 'hemolytic uremic syndrome', can be associated with, or triggered by, conditions such as verocytotoxin-producing Escherichia coli, viral infections, malignant hypertension, scleroderma, allograft rejection, lupus erythematosus, pregnancy, and medications including mitomycin C, calcineurin inhibitors, and oral contraceptives. After renal transplantation, it can occur, as either a de novo episode, or recurrent disease. Calcineurin inhibitors have long been associated with post-transplantation thrombotic microangiopathy. Sirolimus has been used as a primary immunosuppressant in patients transplanted with a history of earlier hemolytic-uremic syndrome, and also as rescue therapy in patients with calcineurin-inhibitor-associated thrombotic microangiopathy. We describe four cases where there was significant thrombotic microangiopathy in the context of contemporaneous or contiguous calcineurin inhibitor and sirolimus usage. As the intrarenal cyclosporin concentration is thought to be significantly elevated when cyclosporin and sirolimus are used together, this may explain these findings, and mandates caution in their co-administration. 相似文献
40.