Impact of mycophenolate mofetil on recurrent rejection in kidney transplant patients

PURPOSE: Mycophenolate mofetil (MMF) has emerged as a valuable adjunctive agent in renal transplantation. However, due to intolerable adverse effects associated with MMF use in our transplant population, we have used MMF selectively in patients at high risk for recurrent graft rejection, since these patients are known to be at risk for poor long-term graft outcomes. The purpose of this study was to assess the efficacy of MMF in preventing the recurrence of acute rejection following an initial rejection episode in kidney transplant patients in the first year following transplantation. METHODS: Forty-four kidney transplant recipients were given MMF prospectively following treatment of their initial rejection episode to prevent recurrent rejection. MMF 1-2 g/d was given. Doses were adjusted based on tolerance; MMF therapy was to be continued for at least 6 months. The control group consisted of 124 consecutive kidney transplant recipients who had received standard anti-rejection therapy without the addition of MMF. Maintenance immunosuppression consisted predominantly of cyclosporine, prednisone+/-azathioprine. Anti-rejection therapy for both groups consisted of either corticosteroids (methylprednisolone 500 mg i.v. for 3 d or oral prednisone 2 mg/kg/d with rapid taper over 3 wk), OKT3 5 mg/d for 10 d or ATG 15 mg/kg/d for 10 d. All rejection episodes were confirmed by biopsy. RESULTS: The majority of rejection episodes were characterized histologically as mild or moderate. Most patients (76%) received corticosteroids for treatment of their first rejection episode. There was a 68% reduction in the incidence of recurrent rejection episodes within the first year of transplant in patients receiving MMF; only 14% of recipients receiving MMF developed recurrent rejection compared to 44% of patients in the control group (p<0.05). Approximately 50% of patients developed MMF-associated adverse effects (leukopenia, GI toxicity). Only 52% of patients remained on MMF at 6 months. One-yr graft survival was 86% in the MMF group and 89% in the control group (p>0.05). One-year patient survival was 93 and 100%, respectively (p>0.05). CONCLUSIONS: The addition of MMF to maintenance therapy for patients experiencing acute renal allograft rejection may prevent recurrent rejection episodes in the subsequent follow-up year.     

炎症在启动和维持心房颤动中的地位——对研究资料的系统回顾

近年的研究显示,炎症在启动、维持心房颤动(房颤)中起非常重要的作用.美国Issac等对1995～2007年间以英文发表的有关房颤与炎症关系方面的文章,以及药物,如他汀类、血管紧张素转化酶抑制剂(ACEI)及糖皮质激素在治疗房颤中的作用方面的文章进行了系统回顾(J Am Coll Cardiol,2007, 50:2021-2028).     

Kinetics and 28-day test–retest repeatability and reproducibility of [11C]UCB-J PET brain imaging

[¹¹C]UCB-J is a novel radioligand that binds to synaptic vesicle glycoprotein 2A (SV2A). The main objective of this study was to determine the 28-day test–retest repeatability (TRT) of quantitative [¹¹C]UCB-J brain positron emission tomography (PET) imaging in Alzheimer’s disease (AD) patients and healthy controls (HCs). Nine HCs and eight AD patients underwent two 60 min dynamic [¹¹C]UCB-J PET scans with arterial sampling with an interval of 28 days. The optimal tracer kinetic model was assessed using the Akaike criteria (AIC). Micro-/macro-parameters such as tracer delivery (K₁) and volume of distribution (V_T) were estimated using the optimal model. Data were also analysed for simplified reference tissue model (SRTM) with centrum semi-ovale (white matter) as reference region. Based on AIC, both 1T2k_V_B and 2T4k_V_B described the [¹¹C]UCB-J kinetics equally well. Analysis showed that whole-brain grey matter TRT for V_T, DVR and SRTM BP_ND were –2.2% ± 8.5, 0.4% ± 12.0 and –8.0% ± 10.2, averaged over all subjects. [¹¹C]UCB-J kinetics can be well described by a 1T2k_V_B model, and a 60 min scan duration was sufficient to obtain reliable estimates for both plasma input and reference tissue models. TRT for V_T, DVR and BP_ND was <15% (1SD) averaged over all subjects and indicates adequate quantitative repeatability of [¹¹C]UCB-J PET.     

Denosumab and osteonecrosis of the jaws – the pharmacology,pathogenesis and a report of two cases

Denosumab (Amgen, Thousand Oaks, California, USA) is a new bone antiresorptive agent used in patients with osteoporosis or metastatic cancer to the bones. As with the bisphosphonates that are used as antiresorptive medications, denosumab has been associated with osteonecrosis of the jaws (ONJ). Over the past two years there has been an increase in the literature describing ONJ in patients receiving agents such as denosumab. Due to promising study results that demonstrate the effectiveness of denosumab in avoiding skeletal complications related to osteoporosis and metastatic bone disease, more patients will receive denosumab in the future. It is reported that this has the potential to become a comparable challenge to bisphosphonate related osteonecrosis of the jaws (BRONJ) for clinicians. This article describes the management of two patients that developed ONJ while receiving denosumab, reviews the incidence of ONJ associated with denosumab, and contrasts the pharmacokinetics of denosumab and the bisphosphonates. The importance of avoiding interventional dental treatment until denosumab has been withdrawn for six months cannot be overstated.     

Role of endothelium in the abnormal response of mesenteric vessels in rats with portal hypertension and liver cirrhosis

BACKGROUND & AIMS: Previous studies have shown that nitric oxide synthesis inhibition corrects the hyporesponsiveness to vasoconstrictors present in the mesenteric vascular bed of portal- hypertensive rats. The origin of this elevated NO production, whether endothelial or muscular, is unknown. The aim of this study was to evaluate the role of vascular endothelium in the hyporesponsiveness to methoxamine (MTX) in the mesenteric vascular bed of portal vein-ligated (PVL) and cirrhotic rats. METHODS: Endothelial denudation was achieved using a combined treatment of cholic acid and distilled water. RESULTS: Compared with the respective control groups, PVL rats showed a reduced vascular response to MTX. Similar results were obtained in cirrhotic animals. The presence of ascites was associated with a more severe reduction in the response to MTX. Removal of the endothelium completely corrected the vascular hyporesponsiveness of PVL, cirrhotic nonascitic, and ascitic animals. In these experiments, acetylcholine-mediated vasodilation was practically absent whereas that of sodium nitroprusside was potentiated, which indicates a successful elimination of the endothelium and the preservation of smooth muscle function. Immunostaining for NO synthase isoforms revealed the presence of endothelial NO synthase protein in healthy and PVL rats exclusively in the endothelium. CONCLUSIONS: The mesenteric vascular hyporesponsiveness to MTX present in these models of liver diseases and portal hypertension is solely due to endothelium-dependent factors. (Gastroenterology 1996 Dec;111(6):1627-32)     

Assessment of bone ages by the Tanner-Whitehouse method using a computer-aided system

A computer-aided system to estimate bone age based on Fourier analysis was assessed by reference to the original radiographs used to produce the Tanner-Whitehouse 2 (TW2) standards for the radius, ulna and short finger bones. The computer-aided system involved matching a template of each bone to the scanned image of the radiograph. The computer then generated a stage of bone maturity, individual and total bone scores and a value for bone age. The bone ages assessed by the computer-aided system were no different from the original TW2 reference values, indicating the applicability of the system. The system was used to assess the bone ages of tall Dutch girls, and the results obtained were compared with more traditional assessments made by an experienced rater. For the radiographs from the tall girls, there was good agreement for individual bones between this method and the traditional assessment by the rater, but less agreement for the total 13-bone score and bone age.     

Longitudinal anthropometric study in children with acute lymphoblastic leukaemia

In four groups of patients with acute lymphoblastic leukaemia, anthropometric variables were investigated every 3 months for 2 years. Group 1 (n = 7) was treated with a high-risk protocol, group 2 (n = 13) with a standard-risk protocol including cranial irradiation, group 3 (n = 13) with a standard-risk protocol without cranial irradiation and group 4 (n = 8) was followed after completion of treatment. A height retardation of 0.4-0.6 SD was observed during therapy in groups 1-3. A catch-up of 0.5 SD was found in group 4. The retardation of armspan was significantly larger than the retardation of sitting height when groups 1-3 were taken together. Head circumference was not affected. The anthropometric variables reflecting nutritional status showed a growth above normal during and after treatment. Corticosteroid medication and not cranial irradiation is the most likely explanation for our findings.