This article reviews the mechanisms by which glucosinolate breakdown products are thought to inhibit carcinogenesis. It describes how isothiocyanates, thiocyanates, nitriles, cyano-epithioalkanes and indoles are produced from glucosinolates through the actions of myrosinase, epithiospecifier protein and epithiospecifier modifier protein released from cruciferous vegetables during injury to the plant. The various biological activities displayed by these phytochemicals are described. In particular, their abilities to induce cytoprotective genes, mediated by the Nrf2 (NF-E2 related factor 2) and AhR (arylhydrocarbon receptor) transcription factors, and their abilities to repress NF-kappaB (nuclear factor-kappaB) activity, inhibit histone deacetylase, and inhibit cytochrome P450 are outlined. Isothiocyanates appear to alter gene expression through modification of critical thiols in regulatory proteins such as Keap1 (Kelch-like ECH-associated protein 1) or IKK (IkappaB kinase), causing activation of Nrf2 and inactivation of NF-kappaB, respectively. Certain indoles act as ligands for AhR. Isothiocyanates and indoles are also capable of affecting cell cycle arrest and stimulating apoptosis. The mechanisms responsible for these anti-proliferative responses are discussed.

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Object Despite the growing use of multimodal intraoperative monitoring (IOM) in cervical spinal surgery, limited data exist regarding the sensitivity, specificity, and predictive values of such a technique in detecting new neurological deficits in this setting. The authors sought to define the incidence of significant intraoperative electrophysiological changes and new postoperative neurological deficits in a cohort of patients undergoing cervical surgery. Methods The authors conducted a prospective analysis of a consecutive series of patients who had undergone cervical surgery during a 5-year period at a university-based neurosurgical unit, in which multimodal IOM was recorded. Sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) were determined using standard Bayesian techniques. The study population included 1055 patients (614 male and 441 female) with a mean age of 55 years. Results The IOM modalities performed included somatosensory evoked potential (SSEP) recording in 1055 patients, motor evoked potential (MEP) recording in 26, and electromyography (EMG) in 427. Twenty-six patients (2.5%) had significant SSEP changes. Electromyographic activity was transient in 212 patients (49.6%), and 115 patients (26.9%) had sustained burst or train activity. New postoperative neurological deficits occurred in 34 patients (3.2%): 6 had combined sensory and motor deficits, 7 had new sensory deficits, 9 had increased motor weakness, and 12 had new root deficits. Of these 34 patients, 12 had spinal tumors, of which 7 were intramedullary. Overall, of the 34 new postoperative deficits, 21 completely resolved, 9 partially resolved, and 4 had no improvement. The deficits that completely resolved did so on average 3.3 months after surgery. Patients with deficits that did not fully resolve (partial or no improvement) were followed up for an average of 1.8 years after surgery. Somatosensory evoked potentials had a sensitivity of 52%, a specificity of 100%, a PPV of 100%, and an NPV of 97%. Motor evoked potential sensitivity was 100%, specificity 96%, PPV 96%, and NPV 100%. Electromyography had a sensitivity of 46%, specificity of 73%, PPV of 3%, and an NPV of 97%. Conclusions Combined neurophysiological IOM with EMG and SSEP recording and the selective use of MEPs is helpful for predicting and possibly preventing neurological injury during cervical spine surgery.

MIS decompression alone for leg dominant symptoms is a clinically effective procedure in the majority of patients including those with degenerative spondylolisthesis or scoliosis. However, patients with scoliosis, particularly those with lateral listhesis, have a significantly higher revision rate that needs to be considered in operative decision-making.

The mechanism by which genotoxic stress induces IRF-1 and the signalling components upstream of this antioncogenic transcription factor during the response to DNA damage are not known. We demonstrate that IRF-1 and the tumour suppressor protein p53 are coordinately up-regulated during the response to DNA damage in an ATM-dependent manner. Induction of IRF-1 protein by either ionizing radiation (IR) or etoposide occurs through a concerted mechanism involving increased IRF-1 expression/synthesis and an increase in the half-life of the IRF-1 protein. A striking defect in the induction of both IRF-1 mRNA and IRF-1 protein was observed in ATM deficient cells. Although ATM deficient cells failed to increase IRF-1 in response to genotoxic stress, the induction of IRF-1 in response to viral mimetics remained intact. Re-expression of the ATM kinase in AT cells restored the DNA damage inducibility of IRF-1, whilst the PI-3 kinase inhibitor wortmannin inhibited IRF-1 induction by DNA damage in ATM-positive cells. The data highlight a role for the ATM kinase in orchestrating the coordinated induction and transcriptional cooperation of IRF-1 and p53 to regulate p21 expression. Thus, IRF-1 is controlled by two distinct signalling pathways; a JAK/STAT-signalling pathway in viral infected cells and an ATM-signalling pathway in DNA damaged cells.

The objective of the investigation was to report on the health-related quality of life (HRQoL) of patients diagnosed with skull base tumours using the Short Form Health Survey questionnaire (SF-36). Those patients suffering with vestibular schwannoma were examined to determine the effect facial nerve function had on their quality of life. It took place at the tertiary referral centre at the Department of Clinical Neurosciences, Western General Hospital, Edinburgh. A prospective study of 70 consecutive patients was taken, who harboured the following tumours: 54 vestibular schwannomas, 13 meningiomas, two haemangioblastomas and one hypoglossal schwannoma. Patients were interviewed using the short form 36 (SF-36) questionnaire. Facial nerve function was assessed in those patients who had vestibular schwannomas. The entire cohort of live skull base patients were assessed after a median follow-up time of 38.4 months. Patients with vestibular schwannoma treated conservatively with interval MRI had a quality of life similar to t he normal population. Those who underwent surgery had a significant difference in two of the SF-36 domains. No statistically significant correlation was found at final assessment between the degree of facial nerve functioning and any of the domains of SF-36. Patients with non-vestibular tumours had an impaired HRQoL in seven of the eight domains. Patients with skull base tumours have a significant impairment of their HRQoL. A conservative policy of follow up with interval MRI for patients with small vestibular schwannomas may therefore be more appropriate to preserve their HRQoL. Facial nerve outcome has little influence on quality of life in vestibular schwannoma patients.

Pedicle screw fixation has achieved significant popularity amongst spinal surgeons for both single and multi-level spinal fusion. Misplacement and pedicle cortical violation occurs in over 20% of screw placement and can result in potential complications such as dysthesia, paraparesis or paraplegia. There have been many advances in techniques available for navigating through the pedicle; however, these techniques are not without drawbacks. A new electrical conductivity-measuring device, previously evaluated on the porcine model to detect the pedicle violation, was evaluated amongst nine European Hospitals to be used in conjunction with the methods currently used in that centre. This new device is based on two original principles; the device is integrated in the drilling or screwing tool. The technology allows real-time detection of perforation through two independent parameters, impedance variation and evoked muscle contractions. Data was collected twofold. Initially, the surgeon was given the device and a comparison was made between the devices ability to detect a breech and the surgeon's ability to detect one using his traditional methods of pedicle preparation. In the second module of the study, the surgeon was limited to using the electrical conductivity detection device as their sole guide to detect pedicle breaches. A comparison was made between the detection ability of the device and the other detection possibilities. Post-operative fine cut CT scanning was used to detect the pedicle breaches. Overall, the 11 trial surgeons performed a total of 521 pedicle drillings on 97 patients. Initially there were 147 drillings with 23 breaches detected. The detection rate of these breaches were 22/23 for the device compared to 10/23 by the surgeon. Over both parts of the study 64 breaches (12.3%) were confirmed on post-operative CT imaging. The electrical conductivity detection device detected 63 of the 64 breaches (98.4%). There was one false negative and four false positives. This gives the device an overall sensitivity of 98% and specificity of 99% for detecting a pedicle breach. The negative predictive value was 99.8%, with a positive predictive value of 94%. No adverse event was noted with the use of the electrical conductivity device. Electrical conductivity monitoring may provide a

Ten patients received liver transplants for unresectable epithelioid hemangioendothelioma (EHE). At the time of transplantation, four patients had microscopic metastases to the hilar lymph nodes, and one of the four also had metastases to a rib. The fifth patient had metastases to the lung, pleura, and diaphragm. The remaining five patients were believed to be free of metastatic disease. Two of these five patients died of metastatic disease at 3 and 16 months, respectively, after transplantation. Interestingly, all five patients with metastatic involvement are currently alive 40.6 +/- 22 months (mean +/- standard error of mean [SEM]) after transplantation, although one of these patients currently has metastatic disease to the lungs and mediastinum. Thus, the projected 5-year actuarial survival rate is 76%, with two patients at risk after the third year. In conclusion, liver transplantation is a reasonable procedure for bulky, otherwise unresectable, EHE even in the presence of metastatic disease.