Acute rejection episodes after renal transplantation are an important clinical challenge, despite use of multidrug immunosuppressive regimens. We did a prospective, multicentre, randomised, ...double-blind trial to investigate the impact of the addition of sirolimus, compared with azathioprine, to a ciclosporin and prednisone regimen.
719 recipients of primary HLA-mismatched cadaveric or living-donor renal allografts who displayed initial graft function were randomly assigned, after transplantation, sirolimus 2 mg daily (n=284) or 5 mg daily (n=274), or azathioprine (n=161). We assessed the primary composite endpoint of efficacy failure, occurrence of biopsy-confirmed acute rejection episodes, graft loss, or death, and various secondary endpoints that characterise these episodes at 6 months and 12 months. Analyses were done by intention to treat.
The rate of efficacy failure at 6 months was lower in the two sirolimus groups (2 mg 18·7%, p=0·002; 5 mg 16·8%, p<0·001) than in the azathioprine group (32·3%). The frequency of biopsy-confirmed acute rejection episodes was also lower (2 mg 16·9%, p=0·002; 5 mg 12·0%, p<0·001; azathioprine 29·8%). At 12 months, survival was similar in all groups for grafts (97·2%, 96·0%, and 98·1%) and patients (94·7%, 92·7%, and 93·8%). Patients on sirolimus showed a delay in the time to first acute rejection episode and decreased frequency of moderate and severe histological grades of rejection episodes and related antibody treatment, compared with the azathioprine group. Rates of infection and malignant disorders were similar in all groups.
Use of sirolimus reduced occurrence and severity of biopsy-confirmed acute rejection episodes with no increase in complications. Further studies are needed to establish the optimum doses for the combined regimen.
The current study was designed to investigate our hypotheses that balloon-expandable covered stents display acceptable function over longitudinal follow-up in patients with complex vascular pathology ...and provide a suitable alternative for the treatment of recurrent in-stent restenosis. All stents were Atrium iCast, which is a balloon-mounted, polytetrafluoroethylene-covered stent with a 6F/7F delivery system. A retrospective review was performed of 49 patients with 66 stented lesions. Data were analyzed with life tables and t-tests. The most commonly treated vessels were the iliac (61%) and renal (24%) arteries. Indications for covered stent placement were unstable atheromatous lesions (50%), recurrent in-stent restenosis (24%), aneurysm (8%), aortic bifurcation reconstruction (7.5%), dissection (4.5%), endovascular aneurysm repair-related (4.5%), and stent fracture (1.5%). Patency was assessed by angiogram or duplex ultrasonography. The primary end point was patency and secondary end points were technical success and access-site complications. Mean follow-up was 13 months (range 1.5-25). The technical success rate was 97%. Unsuccessful outcomes were due to deployment error (n=1) and stent malpositioning (n=1). The cohort (n=64) 6- and 12-month primary patency rates were 96% and 84%, respectively. Twelve-month assisted primary patency was 98%. Iliac artery stents (n=38) had a primary patency of 97% at 6 months and 84% at 12 months with an assisted primary patency of 100% at 12 months. Renal artery stents (n=16) had a primary patency of 92% at 6 months and 72% at 12 months with an assisted primary patency of 92% at 6 and 12 months. Stents placed for recurrent in-stent restenosis (n=16) had a primary patency of 85%, assisted primary patency of 93%, and a 15% restenosis rate at 12 months. Specifically, stents placed for renal artery recurrent in-stent restenosis (n=10) had a primary patency of 73%, assisted primary patency of 82%, and a restenosis rate of 27%. The restenosis rate included two renal artery occlusions in patients noncompliant with clopidogrel use and resulted in ipsilateral kidney loss in both patients. In-stent peak systolic velocities decreased significantly (p<0.05) from preoperation to 12 months in iliac stents and to 18 months in renal stents. Ankle-brachial index increased significantly in iliac stents from preoperation (0.62+/-0.18) to 18 months (0.86+/-0.16). Successful exclusion of atheromatous lesions and aneurysm/dissection/endoleak was 100%. Access-site complications occurred in 6%: pseudoaneurysm (n=2), dissection (n=1), and bleeding (n=1). Balloon-expandable covered stents have an acceptable primary patency with an excellent assisted patency after salvage angioplasty. The clinical utility of this technology is broad for the treatment of aneurysms, extravasation, unstable atheromatous lesions, and recurrent in-stent restenosis.
Objective. The aim of this study was to determine whether the prostaglandin synthase inhibitor indomethacin reverses the inflammation and abnormal gallbladder contractility that occur after common ...bile duct ligation (CBDL), a model of acute cholecystitis.
Methods. Gallbladder muscle contractility was studied in vitro in normal, CBDL, and sham-operated guinea pigs. Animals were treated with saline or indomethacin in vivo. Acetylcholine (ACh) was used to directly contract the muscle and electric field stimulation (EFS) to activate intrinsic nerves. Hematoxylin and eosin-stained slides of muscle strips were scored for inflammation.
Results. CBDL in saline-treated animals increased the inflammation score and decreased gallbladder muscle contractility to ACh and EFS. Indomethacin decreased the inflammation score and partly reversed the smooth muscle contractile response to ACh 6 and 24 h after CBDL, but not at 48 h. Indomethacin did not reverse the CBDL-induced decrease in nerve-evoked contractions.
Conclusion. Gallbladder inflammation and contractile dysfunction after CBDL are partly reversed with indomethacin at 6 and 24 h, but not at 48 h. This suggests that, early in the course of CBDL, the inflammation and contractile dysfunction are, in part, prostaglandin-mediated.
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