Long-term outcome after anterior cervical discectomy without fusion

To retrospectively study the long-term outcome of patients after anterior cervical discectomy without fusion (ACD) compared to results published on the long-term outcome after ACD with fusion (ACDF). We reviewed the charts of all patients receiving ACD surgery between 1985 and 2000 to analyze the direct post-operative results as well as complications of the surgery. Moreover, 102 patients, randomly selected, were interviewed with the neck disability index to study possible persisting complaints up to 18 years after ACD surgery. A total of 551 Patients were identified. Two months post-operative follow up at the outpatient clinic revealed that 90.1% of patients were satisfied with the result of ACD surgery. At the time of the survey, this percentage had dropped to 67.6%. In addition, 20.6% and 11.8% had obtained moderate to severe complaints, respectively, in daily-life activities. Complaints were mainly localized in the neck region and occasionally provoked radiating pain in the arm. On the short term, ACD leads to a satisfied outcome. Over the longer term, patients report increasing complaints. The increase in complaints at the time of the survey may be the result of ongoing degenerative effects. Compared to published data on ACDF, there is no superiority of any fusion technique compared to ACD alone

Simvastatin Sodium Salt and Fluvastatin Interact with Human Gap Junction Gamma-3 Protein

Finding pleiomorphic targets for drugs allows new indications or warnings for treatment to be identified. As test of concept, we applied a new chemical genomics approach to uncover additional targets for the widely prescribed lipid-lowering pro-drug simvastatin. We used mRNA extracted from internal mammary artery from patients undergoing coronary artery surgery to prepare a viral cardiovascular protein library, using T7 bacteriophage. We then studied interactions of clones of the bacteriophage, each expressing a different cardiovascular polypeptide, with surface-bound simvastatin in 96-well plates. To maximise likelihood of identifying meaningful interactions between simvastatin and vascular peptides, we used a validated photo-immobilisation method to apply a series of different chemical linkers to bind simvastatin so as to present multiple orientations of its constituent components to potential targets. Three rounds of biopanning identified consistent interaction with the clone expressing part of the gene GJC3, which maps to Homo sapiens chromosome 7, and codes for gap junction gamma-3 protein, also known as connexin 30.2/31.3 (mouse connexin Cx29). Further analysis indicated the binding site to be for the N-terminal domain putatively ‘regulating’ connexin hemichannel and gap junction pores. Using immunohistochemistry we found connexin 30.2/31.3 to be present in samples of artery similar to those used to prepare the bacteriophage library. Surface plasmon resonance revealed that a 25 amino acid synthetic peptide representing the discovered N-terminus did not interact with simvastatin lactone, but did bind to the hydrolysed HMG CoA inhibitor, simvastatin acid. This interaction was also seen for fluvastatin. The gap junction blockers carbenoxolone and flufenamic acid also interacted with the same peptide providing insight into potential site of binding. These findings raise key questions about the functional significance of GJC3 transcripts in the vasculature and other tissues, and this connexin’s role in therapeutic and adverse effects of statins in a range of disease states