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.     

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.     

Non surgical management of pseudoaneurysms

Background: The incidence of pseudoaneurysm has increased due to the large number of vascular procedures performed and the widespread use of anticoagulation therapy during procedures. Non-invasive methods for management of pseudoaneurysms comprise of ultrasound guided compression (USGC), thrombin therapy, arterial embolisation and endovascular stent graft insertion. We discuss our experience in the management of fourteen cases of pseudoaneurysms using non surgical techniques.     

Effect of growth hormone treatment on craniofacial growth in Turner's syndrome

A cephalometric study was performed in 19 patients with Turner's syndrome, aged 8.7–16.5 years. A lateral roentgencephalogram was taken before and after two years of treatment with biosynthetic growth hormone in a dose of 24 IU/m²/week. During two years of growth hormone treatment, the mandibular length increased mainly due to vertical growth. The initially posteriorly rotated mandible showed an anterior rotation, although the normal position was not reached. The other linear measurements and angles did not change during treatment. No indications were found for an increase in the disproportionate growth or for excessive chin growth as a sign of acromegaly during growth hormone treatment. In conclusion, growth hormone treatment in patients with Turner's syndrome resulted in an increase in mandibular length, mainly due to vertical growth of the ramus and in the anterior rotation of the mandible.     

The effects of abdominal and bimanual pelvic examination and transvaginal ultrasonography on serum CA-125 levels

The need for the early detection of ovarian cancer continues to be one of the most important issues in women's health care. The three most extensively evaluated screening methods for ovarian cancer are pelvic examination, transvaginal ultrasonography, and serum CA-125 levels. The answers to questions such as should the levels of CA-125 be measured before bimanual pelvic examination or transvaginal ultrasonography or do abdominal examinations effect the levels of CA-125 are obscure. Fifty-four otherwise healthy female volunteers at the preovulatory phase of the menstrual cycle complaining of vaginal candidiasis were divided into 3 groups. Abdominal (group 1), bimanual pelvic (group 2), and transvaginal ultrasonography (group 3) examination was performed and serum CA-125 levels were evaluated prior to examination and 10 minutes, 6 hours, and 24 hours after the examination. As a result, serum CA-125 levels (U/ml) were found to be 8.13 +/- 4.76, 8.23 +/- 5.05, 8.32 +/- 4.88, and 8.33 +/- 4.94 in the group of abdominal examination, respectively, 8.23 +/- 4.89, 8.45 +/- 5.15, 8.77 +/- 4.96, and 8.79 +/- 5.50 in the group of bimanual pelvic examination, respectively, and 8.19 +/- 4.56, 8.30 +/- 5.10, 8.81 +/- 5.56, and 8.88 +/- 5.71 in the group of transvaginal ultrasonography, respectively. The serum CA-125 levels detected prior to examinations were statistically insignificant when compared with the results obtained at 10 minutes, 6 hours, and 24 hours later in all three groups. We concluded that physical examination, either abdominal or pelvic, and transvaginal ultrasonography do not change the serum levels of CA-125.