Techniques for high-resolution MR imaging of atherosclerotic plaque

Atherosclerotic cardiovascular disease is the most common cause of death in the United States. Investigation of atherosclerotic plaque morphology and composition is important because the findings may be useful in predicting prognosis or response to therapy. This study presents high-resolution magnetic resonance (MR) imaging techniques developed on a 1.5-T whole-body imager with a custom-built surface coil, for characterizing the composition and morphology of plaque removed at carotid endarterectomy. The initial comparison of MR imaging and histologic results showed good correlation. In conjunction with MR angiography, these techniques could be used in in vivo imaging to define the size, location, and contents of atherosclerotic plaque at the carotid bifurcation.     

Evidence for Kidney Rejection After Combined Bone Marrow and Renal Transplantation Despite Ongoing Whole‐Blood Chimerism in Rhesus Macaques

Although there is evidence linking hematopoietic chimerism induction and solid organ transplant tolerance, the mechanistic requirements for chimerism‐induced tolerance are not clearly elucidated. To address this, we used an MHC‐defined primate model to determine the impact of impermanent, T cell‐poor, mixed‐chimerism on renal allograft survival. We compared two cohorts: one receiving a bone marrow and renal transplant (“BMT/renal”) and one receiving only a renal transplant. Both cohorts received maintenance immunosuppression with CD28/CD40‐directed costimulation blockade and sirolimus. As previously demonstrated, this transplant strategy consistently induced compartmentalized donor chimerism, (significant whole‐blood chimerism, lacking T cell chimerism). This chimerism was not sufficient to prolong renal allograft acceptance: the BMT/renal mean survival time (MST, 76 days) was not significantly different than the renal transplant alone MST (85 days, p = 0.46), with histopathology documenting T cell mediated rejection. Flow cytometric analysis revealed significant enrichment for CD28–/CD95+ CD4+ and CD8+ Tem cells in the rejected kidney, suggesting a link between CD28‐negative Tem and costimulation blockade‐resistant rejection. These results suggest that in some settings, transient T cell‐poor chimerism is not sufficient to induce tolerance to a concurrently placed renal allograft and that the presence of this chimerism per se is not an independent biomarker to identify tolerance.     

Bilateral testicular cancer: a preventable problem? Experience from a large cancer centre

OBJECTIVE: To report a retrospective review of patients with a testicular germ cell tumour treated in a large cancer centre who developed a second tumour, as 1.8-5% of such patients will subsequently develop a new primary tumour in the contralateral testis. PATIENTS AND METHODS: From a database of 570 men treated for testicular cancer in the West of Scotland between 1989 and 1998, all those who developed bilateral testicular tumours were identified. RESULTS: Nineteen men (3.3%) developed a second primary testicular malignancy; the mean age at diagnosis of the first tumour was 29.5 years, with the mean (range) interval to diagnosis of the second tumour of 76 (11-181) months (except for one man with synchronous tumours). The first tumour was teratoma in 11 and seminoma in seven; one patient had synchronous bilateral teratoma. The second primary was teratoma in 10 and seminoma in eight. Known risk factors for carcinoma in situ were present in nine patients, i.e. a small atrophic contralateral testis in five, a family history of testicular cancer in two, a history of infertility in two and unilateral undescended testis in one. Two patients had had contralateral testicular biopsies at the first diagnosis; both were negative for intratubular germ cell neoplasia (IGCN). Eight patients had chemotherapy to treat the first tumour and 14 for the second. All underwent bilateral orchidectomy. Overall, 18 of 19 men are alive and disease-free, with a median follow-up of 51 months. Pathology for 12 of the second testicular tumours was available for review; there was no IGCN in any of the slides from three patients, it was only present focally around the tumour in seven, and was diffuse in two patients. CONCLUSIONS: Chemotherapy for the first testicular tumour does not eliminate the risk of developing a contralateral tumour. Despite careful follow-up, in most patients the second primary tumour was not diagnosed early enough to avoid chemotherapy. The focal nature of IGCN in the second testis in most patients questions the value of biopsy of the contralateral testis. Improved methods of detecting patients at risk of second testicular tumours are needed.     

Myocardial T measurement in iron‐overloaded thalassemia: An ex vivo study to investigate optimal methods of quantification

Myocardial T measurement has been increasingly used for iron quantification to assess the risk of cardiac complications in thalassemia patients. In this study the noise effects were evaluated along with different curve‐fitting models on an iron overloaded ex vivo heart in order to determine the optimal method of T measurement and to help understand issues affecting reproducibility and accuracy. Gradient multiecho short axis images were acquired with differing numbers of excitations to generate varying signal‐to‐noise ratio (SNR) images. A noise correction method was implemented; linear and nonlinear curve‐fitting algorithms were compared and different curve‐fitting models (monoexponential, truncation, baseline subtraction, and offset) were evaluated. This study suggests that the T decay curve in an ex vivo heart can be fitted by a monoexponential model and accurate T measurements can be obtained with proper noise correction. With MRI noise, T is generally overestimated by including late low SNR data points, but underestimated by the offset or baseline subtraction models, which are in fact equivalent. In this situation the truncation model proves to be reproducible and more accurate than the other models. The study also shows that the nonlinear algorithm is preferred in T curve fitting. Magn Reson Med 60:350–356, 2008. © 2008 Wiley‐Liss, Inc.     

A randomised,controlled trial of cemented versus cementless press-fit condylar total knee replacement. Ten-year survival analysis

We have carried out a long-term survival analysis of a prospective, randomised trial comparing cemented with cementless fixation of press-fit condylar primary total knee replacements. A consecutive series of 501 replacements received either cemented (219 patients, 277 implants) or cementless (177 patients, 224 implants) fixation. The patients were contacted at a mean follow-up of 7.4 years (2.7 to 13.0) to establish the rate of survival of the implant. The ten-year survival was compared using life-table and Cox's proportional hazard analysis. No patient was lost to follow-up. The survival at ten years was 95.3% (95% CI 90.3 to 97.8) and 95.6% (95% CI 89.5 to 98.2) in the cemented and cementless groups, respectively. The hazard ratio for failure in cemented compared with cementless prostheses was 0.97 (95% CI 0.36 to 2.6). A comparison of the clinical outcome at ten years in 80 knees showed no difference between the two groups. The survival of the press-fit condylar total knee replacement at ten years is good irrespective of the method of fixation and brings into question the use of more expensive cementless implants.     

Workshop on Late Renal Allograft Dysfunction

Despite continued improvement in incidence of acute immune injury and short-term graft survival, late allograft dysfunction remains a significant problem in the renal transplant population. Recent reports suggest that rates of renal function decline are quite varied in the overall recipient population, and that individual rates for many recipients may not change substantially over time. Moreover, analyses also reveal distinct predictive factors for both early and late functional decline. Long-term outcome studies for renal transplantation, however, might be significantly limited by incomplete data sets for assessing clinical endpoints. In view of the heterogeneous factors that may cause progressive allograft injury, more routine biopsy sampling would allow a more complete characterization of induced injuries. Elucidating mechanisms of renal fibrosis in response to injury, in experimental systems and humans, is also an important goal in better understanding chronic allograft damage. Regulation of cell senescence genes and epithelial to mesenchymal transition, studied in other models of renal fibrosis, are likely relevant to studies of renal allograft dysfunction. Recent technical advances in analyzing biological samples may play a pivotal role in identifying and validating surrogate markers of allograft function for future interventional trials in transplantation.     

Endovascular management of traumatic thoracic aortic injuries.

BACKGROUND: Endovascular surgery has recently been extended to the treatment of blunt traumatic aortic injuries. Since most of these injuries occur at the aortic isthmus, graft fixation in proximity to the origin of the left subclavian artery (LSA) has been a concern. Covering the LSA with graft fabric lengthens the proximal fixation site and should minimize proximal endoleaks. We therefore wished to evaluate the feasibility and safety of endovascular repair of thoracic aortic injuries after blunt trauma, both with and without deliberate coverage of the LSA. METHODS: At a tertiary care teaching hospital in London, Ont., we reviewed our experience with endovascular repair of 7 traumatic aortic injuries. We reviewed the technical success rate and the incidence of left subclavian coverage. Major morbidity, including rates of paraplegia and death were noted. The patients were followed-up with serial CT to look for endoleaks, stent migration or aneurysm growth and to determine whether they had symptoms related to left subclavian coverage. RESULTS: The time from injury to treatment ranged from 7 hours to 7 days (mean 36 h). The mean Injury Severity Score was 36. All injuries were at the aortic isthmus, and among the 7 patients treated, 6 had deliberate coverage of the LSA. One patient underwent carotid-to-subclavian artery bypass, but the other 5 did not. There were no cases of paraplegia; 1 patient had symptoms of claudication in the left arm but did not want revascularization. No procedure-related complications occurred, and all patients survived the event. Follow-up ranged from 2 to 30 (mean 13) months, and no endoleaks, stent migration or aneurysm expansion were noted in follow-up. CONCLUSIONS: Although long-term results are unknown, we conclude that endovascular repair of traumatic aortic injuries after blunt trauma can be performed safely with low morbidity and mortality and that coverage of the LSA without revascularization is tolerated by most patients.