An aggressive policy of bilateral saphenous vein harvest for infragenicular revascularisation in the era of multidrug resistant bacteria

Background: The success of infragenicular revascularisation for lower limb ischaemia is limited by the high proportion of patients without ipsilateral long saphenous vein (LSV) of adequate length or quality. The aim of this study was to report the results of an autogenous vein only policy for infragenicular revascularisation utilising contralateral LSV when ipsilateral LSV is inadequate. The treatment and outcome of infection of autogenous grafts with methicillin resistant Staphylococcus aureus (MRSA) is also reported. Patients and methods: The vascular audit database and patient case notes were reviewed retrospectively for patients with arterial occlusive disease requiring infragenicular reconstruction. There were 68 critically ischaemic legs in 65 patients of whom 48 were male: median age (range) 74 years (41–94), over a three year period. Results: Thirty six patients (53%) underwent revascularisation (eight infragenicular femoropopliteal bypass, 28 femorodistal), 24 (35%) underwent primary amputation and a further eight (12%) were found to have unsuitable distal vessels for revascularisation after tibial vessel exploration and intraoperative angiography. Thirty three grafts (92%) utilised LSV and three (8%) were polytetrafluoroethylene grafts. Thirteen patients (39%) lacked adequate ipsilateral LSV of whom 12 had the contralateral leg explored providing suitable LSV in 10/12 (83%). Contralateral LSV was used as a single length conduit in two cases and as a venovenous composite graft in eight cases. Primary, primary assisted, and secondary patency rates at two years were 38%, 77%, and 81% respectively. Actuarial limb survival and patient survival rates at two years were 86% and 61% respectively. Eleven patients developed ipsilateral wound complications (30%) including seven (21%) who developed MRSA infection of the ipsilateral leg wound. MRSA wound infection was treated successfully in all cases by antibiotic therapy (intravenous vancomycin). No patient subsequently required saphenous vein harvesting for a secondary reconstruction or coronary artery bypass graft. Conclusion: Excellent long term results can be achieved using autogenous vein for infragenicular revascularisation and the contralateral LSV is an excellent alternative in the absence of suitable ipsilateral LSV. Autogenous vein may confer some protection against severe complications observed with MRSA infection seen in vascular patients and therefore its use is recommended

A case of Lenvatinib-induced Focal Segmental Glomerulosclerosis (FSGS) in metastatic medullary thyroid cancer.

We describe a case of lenvatinib (E7080) associated focal segmental glomerulosclerosis (FSGS) encountered during the treatment of metastatic medullary thyroid cancer. Proteinuria is a relatively common side effect of VEGF-targeted treatments and can occasionally result in treatment discontinuation. Here, we describe a patient who developed secondary FSGS necessitating discontinuation of treatment at first but who was subsequently rechallenged with anti-VEGF-targeted treatment without recurrence of proteinuria. Lenvatinib was a novel experimental agent at the time the treatment took place; however, its recent licensing for the treatment of thyroid malignancies in the UK makes reporting of these adverse effects all the more important now

Role of extracellular signal-regulated kinase 5 (ERK5) in human breast cancer

Abstract Abstract #4042 Background&amp;#x2028; ERK5 is a novel member of the mitogen-activated protein kinase (MAPK) family. MAPKs regulate multiple cellular functions, including proliferation, differentiation and survival. Recent studies have implicated the ERK5 pathway in human breast cancer. As breast cancer is now the most common type of cancer in the UK, research into this potential biomarker is essential.&amp;#x2028; Method&amp;#x2028; An optimised immunohistochemistry protocol (McCracken S. Oncogene 2008) was applied to examine expression of ERK5 in a cohort of 10 normal breast samples and 402 estrogen receptor (ER) positive breast cancer specimens from patients treated with Tamoxifen. ERK immunoreactivity was quantified using a weighted histoscore method (Kirkegaard T. Histopathology 2006), and the data was corroborated to clinico-pathologic parameters including the HER family (Tovey S. Clin Can Res. 2005).&amp;#x2028; Results&amp;#x2028; Of 402 tumours on the TMA, 346 cases were informative. Follow-up was available for a minimum of 10 years: 239 with stable disease, 94 cases recurred (13 with bilateral recurrence) and 84 received adjuvant chemotherapy.&amp;#x2028; ERK5 expression in the tumour cohort was observed in the cytoplasm with 78% of samples having weak staining with a histoscore of &amp;lt;100, 20% with moderate staining with a score between 100-200 and 2% with strong staining, histoscore&amp;gt;200. ERK5 expression in the nucleus demonstrated 85% of cores with a histoscore &amp;lt;100 (weak) and 15% between 100-200 (moderate). Almost all ERK5 membrane staining was weak (99% had a histoscore of &amp;lt;100). ERK5 cytoplasmic and nuclear expression were directly associated (c.c.=0.682, p&amp;lt;0.001) and ERK5 nuclear expression showed a trend for association with tumour size (p=0.069). In addition, ERK5 cytoplasmic expression was weakly associated with HER1-3 positivity (p=0.022) and nodal status (p=0.039). Interestingly, both cytoplasmic and nuclear ERK5 expression correlated with cytoplasmic and nuclear ERK1/2 expression (p=0.001 and p=0.003, respectively).&amp;#x2028; All of the benign breast cases expressed cytoplasmic ERK5 at a relatively weak level (100% with a histoscore&amp;lt;100). Again cytoplasmic and nuclear expression in the benign cohort correlated (c.c. =0.879 and p=0.001). Benign and tumour breast tissue expressed significantly different levels of nuclear ERK5 (p=0.002).&amp;#x2028; Discussion &amp;#x2028; This study demonstrates that ERK5 is commonly expressed in breast cancer specimens. ERK5 nuclear expression was shown to be related to tumour size, suggesting a potential role in proliferation. In support of this observation ERK5 expression also strongly correlated with expression of ERK1/2 in this cohort. ERK5 was also shown to be associated with nodal status and HER1-3 expression. Therefore our data supports the need for further investigation into the role of ERK5 in breast cancer, including ER negative patients. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4042.</jats:p

Highly Efficient and Bidirectional Photochromism of Spirooxazine on Au 111

Controlling molecules in direct contact with surfaces is central to molecular electronics. Photochromic molecules immobilized and contacted by a surface promise to provide remote control on the molecular level using light. Combining X-ray absorption spectroscopy, differential reflectance spectroscopy, and density functional theory, we demonstrate highly efficient and bidirectional photochromism of a spirooxazine molecular switch in direct contact with a Au(111) surface. The ring-opening reaction by UV light is 2 orders of magnitude more efficient than previously reported for other surface-adsorbed systems, and even more importantly, the red-light-induced ring-closing is accessible even in contact with a metal surface. This opens new prospects for applications by utilizing the gold surface with directly adsorbed functional units consisting of molecular photochromic switches

Highly Efficient Thermal and Light Induced Spin State Switching of an Fe II Complex in Direct Contact with a Solid Surface

Spin crossover SCO complexes possess a bistable spin state that reacts sensitively to changes in temperature or excitation with light. These effects have been well investigated in solids and solutions, while technological applications require the immobilization and contacting of the molecules at surfaces, which often results in the suppression of the SCO. We report on the thermal and light induced SCO of [Fe bpz 2phen] molecules in direct contact with a highly oriented pyrolytic graphite surface. We are able to switch on the magnetic moment of the molecules by illumination with green light at T 6 K, and off by increasing the temperature to 65 K. The light induced switching process is highly efficient leading to a complete spin conversion from the low spin to the high spin state within a submonolayer of molecules. [Fe bpz 2phen] complexes immobilized on weakly interacting graphite substrates are thus promising candidates to realize the vision of an optically controlled molecular logic unit for spintronic device

MicroRNA-214 antagonism protects against renal fibrosis

Renal tubulointerstitial fibrosis is the common end point of progressive renal disease. MicroRNA (miR)-214 and miR-21 are upregulated in models of renal injury, but the function of miR-214 in this setting and the effect of its manipulation remain unknown. We assessed the effect of inhibiting miR-214 in an animal model of renal fibrosis. In mice, genetic deletion of miR-214 significantly attenuated interstitial fibrosis induced by unilateral ureteral obstruction (UUO). Treatment of wild-type mice with an anti-miR directed against miR-214 (anti-miR-214) before UUO resulted in similar antifibrotic effects, and in vivo biodistribution studies demonstrated that anti–miR-214 accumulated at the highest levels in the kidney. Notably, in vivo inhibition of canonical TGF-β signaling did not alter the regulation of endogenous miR-214 or miR-21. Whereas miR-21 antagonism blocked Smad 2/3 activation, miR-214 antagonism did not, suggesting that miR-214 induces antifibrotic effects independent of Smad 2/3. Furthermore, TGF-β blockade combined with miR-214 deletion afforded additional renal protection. These phenotypic effects of miR-214 depletion were mediated through broad regulation of the transcriptional response to injury, as evidenced by microarray analysis. In human kidney tissue, miR-214 was detected in cells of the glomerulus and tubules as well as in infiltrating immune cells in diseased tissue. These studies demonstrate that miR-214 functions to promote fibrosis in renal injury independent of TGF-β signaling in vivo and that antagonism of miR-214 may represent a novel antifibrotic treatment in the kidney