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Decompressive craniectomy (DC) is an accepted surgical technique for reducing life-threatening levels of intracranial pressure. Remodelling the cranial vault following DC can constitute a reconstructive challenge and is known to carry significant morbidity. The aim of our study was to evaluate acrylic versus autologous cranioplasty with regard to specific complication rates. A retrospective analysis was conducted of 286 consecutive adult patients who underwent cranioplasty following supratentorial decompressive craniectomy at our institution between January 2003 and June 2013. The patients were followed based on medical records, operative reports, imaging and outpatient contacts in the postoperative course. A total of 221/286 patients in our series received an autologous bone flap. 65/286 cranioplasty procedures were carried out using acrylic (PMMA) implants to cover uni- or bilateral defects. Within the follow-up period a total of 100 operative revisions were performed. 33.3% patients in the autologous bone group and 40.6% of patients in the acrylic group developed complications requiring surgical attention. The main reason for revision was infection with a total of 37 revisions necessary to treat disturbed wound healing. Postoperative sub- and epidural hematomas requiring revision were more frequent in the acrylic group. Resorption of the autologous bone flap requiring operative revision was seen in 8/222 (3.6%) cases. Other complications included loosening of the implant or dislocation. From our data it can be concluded that cranioplasty procedures using autologous bone-flaps and acrylic implants carry signifikant morbidity, but that both are justifiable techniques for cranioplasty in adult patients.

Heart and circulatory diseases affect more than seven million people in the UK. Non-invasive cardiac imaging is a critical element of contemporary cardiology practice. Progressive improvements in technology over the last 20 years have increased diagnostic accuracy in all modalities and led to the incorporation of non-invasive imaging into many standard cardiac clinical care pathways. Cardiac imaging tests are requested by a variety of healthcare practitioners and performed in a range of settings from the most advanced hospitals to local health centres. Imaging is used to detect the presence and consequences of cardiovascular disease, as well as to monitor the response to therapies. The previous UK national imaging strategy statement which brought together all of the non-invasive imaging modalities was published in 2010. The purpose of this document is to collate contemporary standards developed by the modality-specific professional organisations which make up the British Cardiovascular Society Imaging Council, bringing together common and essential recommendations. The development process has been inclusive and iterative. Imaging societies (representing both cardiology and radiology) reviewed and agreed on the initial structure. The final document therefore represents a position, which has been generated inclusively, presents rigorous standards, is applicable to clinical practice and deliverable. This document will be of value to a variety of healthcare professionals including imaging departments, the National Health Service or other organisations, regulatory bodies, commissioners and other purchasers of services, and service users, i.e., patients, and their relatives.

Introduction: The efficacy of hip precautions in preventing dislocation post total hip arthroplasty (THA) has been questioned in recent literature. From 2014 our centre ceased routinely prescribing them due to lack of evidence. We investigate the effect of stopping these precautions on dislocation rate, patient satisfaction and Oxford hip score (OHS). Methods: Patients who underwent primary total hip arthroplasty prior to this change in protocol ( n = 2551) and for 1 year subsequently ( n = 673) were identified. Operative records were used to identify key demographic and operative data. Incidence of dislocation, OHS and patient satisfaction were extracted from the centre’s electronic database. Subset analysis of those patients dislocating within 6 weeks was performed. Results: Rate of dislocation at 6 weeks in those prescribed and not prescribed precautions was 0.71% and 0.89% respectively ( p = 0.618). At 1 year this rose to 1.25% and 1.49% ( p = 0.406). Satisfaction ( p = 0.332) and OHS ( p = 0.441) at 1 year was not significantly different between cohorts. Conclusions: Cessation of prescribing routine hip precautions post primary THA does not appear to significantly affect overall dislocation rate, patient satisfaction or functional status at 1 year post-operatively.

Background With over 2.35 million records, the National Joint Registry (NJR) is the largest arthroplasty registry in the world. It provides a powerful tool to monitor implant survivorship and influence different surgical strategies. To date, little work has been undertaken to investigate the validity of the ‘Reason for Revision’ recorded in Consultant Outcome Reports on the NJR. Methods The NJR was queried to identify all revisions on the THR performed at a single centre over an 11-year period. Review and validation of ‘Reason for Revision’ for each case was undertaken using radiological imaging studies, pathology, histology, microbiology and electronic medical records. Results Of the 22,046 primary total hip replacements (THR) and total knee replacements (TKR) undertaken by 23 surgeons at our hospital, over an 11-year period, 1.35% (297) were subsequently reported to the NJR as revised. Discrepancies in reporting to the NJR were identified for 41 cases (25.63%) for THR and 28 (20.40%) cases for TKR. Revision for infection was under-reported for both THR and TKR by 1.88% and 3.65% respectively. Reporting of adverse soft tissue reaction to particulate debris for THR was unreported by 11%. Progressive arthritis following a TKR was unreported by 6.56%. All the cases reported as ‘other’ (8.75% for THRs and 3.65% for TKRs) were reclassified to the most appropriate ‘reason for revision’ category. The ‘reason for revision’ data is recorded to the NJR with findings at the time of surgery. It is some days before microbiology and histology reports become available and source data is not always updated. Conclusion If an average of 23% wrong data entry at a highly organised institution is replicated throughout the UK, a formal process to validate primary and revision data submitted to the NJR should be considered. Local scrutiny, review and validation of revision data are all vital to optimise the value of the NJR. Accurate data recorded to the NJR is imperative to provide safe and effective improvements in orthopaedic surgery.

Background\ud Femoroacetabular impingement syndrome is an important cause of hip pain in young adults. It can be treated by arthroscopic hip surgery, including reshaping the hip, or with physiotherapist-led conservative care. We aimed to compare the clinical effectiveness of hip arthroscopy with best conservative care.\ud \ud Methods\ud UK FASHIoN is a pragmatic, multicentre, assessor-blinded randomised controlled trial, done at 23 National Health Service hospitals in the UK. We enrolled patients with femoroacetabular impingement syndrome who presented at these hospitals. Eligible patients were at least 16 years old, had hip pain with radiographic features of cam or pincer morphology but no osteoarthritis, and were believed to be likely to benefit from hip arthroscopy. Patients with bilateral femoroacetabular impingement syndrome were eligible; only the most symptomatic hip was randomly assigned to treatment and followed-up. Participants were randomly allocated (1:1) to receive hip arthroscopy or personalised hip therapy (an individualised, supervised, and progressive physiotherapist-led programme of conservative care). Randomisation was stratified by impingement type and recruiting centre and was done by research staff at each hospital, using a central telephone randomisation service. Patients and treating clinicians were not masked to treatment allocation, but researchers who collected the outcome assessments and analysed the results were masked. The primary outcome was hip-related quality of life, as measured by the patient-reported International Hip Outcome Tool (iHOT-33) 12 months after randomisation, and analysed in all eligible participants who were allocated to treatment (the intention-to-treat population).\ud \ud This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN64081839, and is closed to recruitment. Findings Between July 20, 2012, and July 15, 2016, we identified 648 eligible patients and recruited 348 participants: 171 participants were allocated to receive hip arthroscopy and 177 to receive personalised hip therapy. Three further patients were excluded from the trial after randomisation because they did not meet the eligibility criteria. Follow-up at the primary outcome assessment was 92% (319 of 348 participants). At 12 months after randomisation, mean iHOT-33 scores had improved from 39·2 (SD 20·9) to 58·8 (27·2) for participants in the hip arthroscopy group, and from 35·6 (18·2) to 49·7 (25·5) in the personalised hip therapy group. In the primary analysis, the mean difference in iHOT-33 scores, adjusted for impingement type, sex, baseline iHOT-33 score, and centre, was 6·8 (95% CI 1·7–12·0) in favour of hip arthroscopy (p=0·0093). This estimate of treatment effect exceeded the minimum clinically important difference (6·1 points). There were 147 patient-reported adverse events (in 100 [72%] of 138 patients) in the hip arthroscopy group) versus 102 events (in 88 [60%] of 146 patients) in the personalised hip therapy group, with muscle soreness being the most common of these (58 [42%] vs 69 [47%]). There were seven serious adverse events reported by participating hospitals. Five (83%) of six serious adverse events in the hip arthroscopy group were related to treatment, and the one in the personalised hip therapy group was not. There were no treatment-related deaths, but one patient in the hip arthroscopy group developed a hip joint infection after surgery. Interpretation Hip arthroscopy and personalised hip therapy both improved hip-related quality of life for patients with femoroacetabular impingement syndrome. Hip arthroscopy led to a greater improvement than did personalised hip therapy, and this difference was clinically significant. Further follow-up will reveal whether the clinical benefits of hip arthroscopy are maintained and whether it is cost effective in the long term.\ud \ud Funding\ud The Health Technology Assessment Programme of the National Institute of Health Research.

Introduction The Elective Orthopaedic Centre in Epsom has an established patient reported outcome measures programme, into which all patients are enrolled. Postoperative complications, Oxford hip/knee scores (OHS/OKS) and EQ-5D™ (EuroQol, Rotterdam, Netherlands) scores are collected up to the second postoperative year. Our population is ageing and the number of joint replacements being performed on the very elderly is rising. The aim of this study was to investigate the outcome of joint replacements in a nonagenarian population. Methods Our dataset was reviewed retrospectively for a cohort of nonagenarians undergoing either a primary total hip replacement (THR) or total knee replacement (TKR) between April 2008 and October 2011. Postoperative complications, mortality rates and functional outcomes were compared with those of a time matched 70–79-year-old cohort. Results Nonagenarians requiring a THR presented with a lower preoperative OHS (p=0.020) but made a greater improvement in the first postoperative year than the younger cohort (p=0.040). The preoperative OKS was lower for nonagenarians than for the control group (p=0.022). At one and two years after TKR, however, there was no significant difference between the age groups. The nonagenarians had a greater risk of requiring a blood transfusion following both THR (p=0.027; 95% confidence interval [CI]: 1.11–5.75) and TKR (p=0.037; 95% CI: 1.08–16.65) while the latter cohort also required a longer stay than their younger counterparts (p=0.001). Mortality rates were higher in the nonagenarian group but these were in keeping with the life expectancy projections identified by the Office for National Statistics. Conclusions Over a two-year period, the functional outcome and satisfaction rates achieved by nonagenarians following a THR or TKR are comparable with 70–79-year-olds.

Outcome in vestibular schwannoma (VS) surgery has improved enormously over the last decades. Surgical positioning remains a matter of discussion. A standardized protocol for diagnostics and management has been applied and evaluated for complications and functional outcome.We examined 502 VS tumors in 483 patients (227 men and 256 women) between 2005 and 2016. According to our patient selection and treatment algorithm, 488 operations (97%) were performed in the semi-sitting position, and 14 (3%) were in the supine position. Auditory and facial functions were analyzed before and after surgery as were perioperative complications.There were 182 patients (36%) with small tumors (Hannover classification T1-T3A) and 320 (64%) large tumors (T3B or T4). Of the patients, 14% were neurofibromatosis type 2 cases. Complete tumor resection was achieved in 96.4%. Hearing preservation occurred in 44% of patients with small tumors and 23% of those with large tumors (Hannover classification), and correlated significantly with tumor size (P0.001). Facial palsy (House Brackmann grades II-VI) was present in 63 patients before and in 185 patients after surgery. Useful facial function (House Brackmann grades I-III) early after surgery was maintained in 86% of patients with small tumors and in 77% of patients with large tumors. Intraoperative complications included air embolism in 45 cases (9%), sinus injury in 3 cases, cerebrospinal fluid leakage in 46 cases (9%), and local hemorrhage in 19 cases (4%). Surgical revision was indicated in 31 cases (6%).In a standardized setting, the semi-sitting position allowed a safe approach. This setting offers the advantage of bimanual tumor nerve handling by the surgeon and an optimal visualization of important functional structures.

Background Early detection of vasospasm (VS) following aneurysmal subarachnoid hemorrhage (aSAH) is vital to trigger therapy and to prevent infarction and subsequent permanent neurological deficit. Although motor evoked potentials (MEPs) are a well-established method for intraoperative detection of cerebral VS and cerebral ischemia during aneurysm surgery, there are no studies investigating the diagnostic value of MEPs for detecting delayed VS following aSAH in an intensive care unit. Objective A prospective study was conceived to assess the diagnostic accuracy of MEPs in comparison with digital subtraction angiography. Methods MEP threshold changes were determined in patients both with and without angiographic VS following high-grade aSAHs. Sensitivity, specificity, and the positive and negative predictive values of significant MEP threshold increases, which indicate angiographic VS, were calculated. Results In all patients experiencing VS of the arteries supplying cerebral motor areas, a minimal MEP threshold increase of 50 mA (mean 66.25 mA) was observed, whereas a maximum MEP threshold increase of 30 mA was observed in patients without VS. Therefore, an increase from a baseline of ≥50 mA was considered significant and resulted in a sensitivity of 0.83, a specificity of 0.92, a positive predictive value of 0.83, and a negative predictive value of 0.92. Conclusion VS following aSAH can be detected accurately by using MEPs. MEPs are a feasible bedside tool for online VS detection in an intensive care unit and, therefore, may complement existing diagnostic tools.

Background Intraoperative imaging of cerebral aneurysms may be desirable in emergency situations with large space-occupying hematomas or to visualize vessels after clip placement. Mobile 3-dimensional fluoroscopes are available in a number of neurosurgical departments and may be useful in combination with simple image postprocessing to depict cerebral vessels. Objective To assess whether intracranial aneurysms are detectable with appropriate image quality with intraoperative 3-dimensional fluoroscopy with intravenous contrast administration. Methods Eight patients were included in the study. The patients' heads were fixed in a radiolucent Mayfield clamp. First, a rotational fluoroscopy scan was performed without contrast agent. Then, a second scan with 50 mL iodine contrast agent was performed. The DICOM (digital imaging and communications in medicine) data of both scans were transferred to an Apple PowerMac workstation, subtracted, and reconstructed with OsiriX imaging software. The images were compared with preoperative angiograms. Results No adverse effects were observed during contrast administration. The entire procedure from fluoroscope positioning to the production of usable 3-dimensional images took 5 to 6 minutes with an image acquisition time of 2 × 24 seconds. The configuration of the aneurysm and the vessel anatomy were assessable. Previous coiling limited image quality in 1 patient. Conclusion This technique quickly provides images of adequate quality to assess the configuration of intracranial aneurysms, which may be helpful when immediate intraoperative information about intracranial vessel pathologies is required. The positioning of the fluoroscope, image acquisition, and processing can be completely integrated into the surgical workflow.

It was the objective of this report to present a case of recurrent aneurysmal subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH) in which an MCA aneurysm was detected by 3D rotational fluoroscopy in an emergency situation. A 44-year-old woman was admitted from an external department after repeated SAH and temporal ICH. Due to progressive anisocoria and cardiocirculatory instability, she was transferred to the operating room without angiography. After a 3D rotational fluoroscopy baseline scan, another scan with 50 ml of iodine contrast agent was performed. The Digital Imaging and Communications in Medicine (DICOM) data sets were subtracted and reconstructed using the OsiriX® free imaging software. No adverse effect was observed during and after the administration of the contrast agent. The entire procedure from positioning of the fluoroscope to the production of utilizable 3D images was completely integrated into the surgical workflow with an image acquisition time of 2 × 24 s. The configuration of the aneurysm, the aneurysm-carrying vessel, and the distal vessel anatomy were well assessable. This technique quickly supplies images at adequate quality to assess the configuration of an intracranial aneurysm and is a useful diagnostic tool if the patient's critical condition prohibits aneurysm diagnostics by angiography or CT angiography.

Patient reported outcome measures (PROMs) are used to gauge clinical performance. The PROMs outcome programme at our centre achieves a preoperative data capture rate of 99%. This falls to 90.6%, 89%, 83% and 79% at the six-week, six-month, one-year and two-year time points, respectively. The study aims were to determine factors associated with patients who did not respond to outcome questionnaires following total hip replacement (THR), and the potential implications this may have when assessing patients following THRs. During the first year of the PROMs programme, 1,322 patients underwent unilateral primary THR at our institution. Of these, 1,311 completed preoperative questionnaires. Thirty-eight patients (2.9%) died within two years of surgery and have been excluded. For the remaining 1,273 patients, we identified those who did not return postoperative questionnaires at each of our review time points. Younger age, lower baseline EQ5D and Oxford Hip scores (OHS) were significantly associated with non-response (p

This study aimed at describing the anatomy of the zona orbicularis (ZO), based on magnetic resonance arthrography (MRA) and magnetic resonance imaging (MRI) scans and to assess the presence of synovial folds in relation to the ZO. A retrospective review was performed using consecutive hip and pelvic MRA and MRI examinations from our institution. We identified 25 normal scans of each variety. Patients were scanned in a neutral hip position and 3D FIESTA sequence images were included in a number of cases. Using electronic callipers, measurements were obtained of the ZO thickness and of the location of the ZO with respect of the femoral head and neck. On MRA, the ZO appeared as a horseshoe in 18/25 patients, being absent anteriorly. On MRI the ZO was less consistent and absent in 12/25 posteriorly, in 8/25 inferiorly and in 2/25 anteriorly. Where present, the ZO usually coincided with the boundary of femoral head sphericity and the narrowest point of the isthmus of the femoral neck. The medial synovial fold was identified in all MRA studies (25/25). The ZO of the hip is most consistently identified when the joint is distended and in approximately 75 % of cases appears as a horseshoe-shaped structure. Superiorly, the ZO is aligned perpendicular to the long axis of the femoral neck. The ZO twists from postero-lateral to antero-medial as it moves inferiorly. Our findings are consistent with the hypothesis that the ZO functions as a ring that resists femoral head distraction and contributes to dynamic circulation of synovial fluid.

Metastasis is the most lethal attribute of cancer,1 and activation of invasion and metastasis is one of the hallmarks of cancer cells.2 Proliferation, deregulated adhesion, increased invasiveness, motility, resistance to apoptotic signals, and the ability to induce angiogenesis are characteristics of metastatic cells.2 Recently, metastasis-associated in colon cancer 1 (MACC1) has been discovered as an independent prognostic indicator of metastasis formation and metastasis-free survival for colon carcinoma patients.3 MACC1 expression is upregulated in malignant colon cancer tissues compared with normal tissues, like colon mucosa or liver, and occurs mainly at the crucial step of transition from the benign to the malignant phenotype.4 It induces cell migration, invasion, proliferation, colony formation, wound healing, and hepatocyte growth factor (HGF)–triggered scattering of colon cancer cells in cell culture. In tumor xenografts it causes tumor growth and metastasis.3,5 It is also discussed that it might be involved in the regulation of apoptosis.6 Mining of databases revealed high MACC1 expression not only in colorectal cancer, but also in pancreatic, ovarian, endometrial, cervical, breast, lung, liver, esophageal, and head and neck cancers.7 Meanwhile, different tumor entities have been analyzed for MACC1 expression by quantitative real-time reverse transcription (RT ) PCR and immunohistochemistry.8 Increased MACC1 expression was shown in advanced colorectal carcinomas,9–11 peritoneal-disseminated gastric carcinomas,12 recurrent lung adenocarcinomas,13,14 and vascular invasive hepatocellular carcinomas.15,16 To the best of our knowledge, there are no data on MACC1 expression in human astrocytic tumors available yet. Diffuse low-grade astrocytomas (LGAs) of World Health Organization (WHO) grade II are well-differentiated tumors with diffuse infiltration of the adjacent brain parenchyma.17 Most of these tumors progress to anaplastic astrocytomas of WHO grade III or glioblastoma multiforme (GBM) of WHO grade IV within 4–5 years after diagnosis.18 This secondary GBM is distinguished from primary GBM, which arises de novo without detectable precursor lesion.19–21 However, GBM are the most prevalent, highly malignant, invasive, and difficult to treat primary brain tumors of adults. The treatment regimens of patients with GBM include neurosurgical tumor resection followed by local γ-irradiation and chemotherapy.17 However, in spite of multidisciplinary treatment, the median survival is only 14.6 months.22,23 Therefore, it is vital to identify new potential therapeutic targets for future therapies. Although these tumors rarely metastasize, their invasive and migratory behaviors are very similar to those of metastatic cells of tumors originating from other tissues. Thus, we hypothesized that MACC1 may also be involved in progression of human gliomas. This hypothesis was supported by the fact that HGF and its receptor c-Met have been shown to be upregulated in high-grade astrocytic tumors,24 thereby inducing migration of their cells.25–28 MACC1 binds to the Sp1 site of the c-Met promoter, controls c-Met promoter activity and expression, and thereby regulates c-Met–mediated signaling.29 Indeed, HGF/c-Met is one of the major signaling cascades regulated by MACC1 in colorectal cancer and is of major importance for both the malignant transformation and metastatic potential of colorectal tumor cells.30 Here we report that MACC1 overexpression promoted proliferation and migration of GBM cells in cell culture. Furthermore, MACC1 overexpression increased the rates of tumor formation in organotypic hippocampal slice cultures (OHSCs) derived from C57BL6/J mice, probably via upregulation of c-Met, as shown by crizotinib inhibitor experiments. In human malignant gliomas, MACC1 expression increased concomitantly with increasing WHO grade. Moreover, MACC1 expression levels allowed discrimination of dormant and recurrent LGAs and of primary and secondary GBM. Most importantly, strong MACC1 protein expression was associated with reduced patient survival. Taken together, these data indicate that MACC1 may represent a promising new biomarker for prognostication and a target for inhibition of proliferation and migration of astrocytic tumor cells.

HIF-1α regulated genes are mainly responsible for tumour resistance to radiation- and chemo-therapy. Among these genes, carbonic anhydrase isoform IX (CA9) is highly over expressed in many types of cancer especially in high grade brain cancer like Glioblastoma (GBM). Inhibition of the enzymatic activity by application of specific chemical CA9 inhibitor sulphonamides (CAI) like Acetazolamide (Aza.), the new sulfonamide derivative carbonic anhydrase inhibitor (SU.D2) or indirect inhibitors like the HIF-1α inhibitor Chetomin or molecular inhibitors like CA9-siRNA are leading to an inhibition of the functional role of CA9 during tumorigenesis. Human GBM cells were treated with in vitro hypoxia (1, 6, or 24 h at 0.1%, O 2 ). Aza. application was at a range between 250 and 8000 nM and the HIF-1α inhibitor Chetomin at a concentration range of 150–500 nM. Cell culture plates were incubated for 24 h under hypoxia (0.1% O 2 ). Further, CA9-siRNA constructs were transiently transfected into GBM cells exposed to extreme hypoxic aeration conditions. CA9 protein expression level was detectable in a cell-type specific manner under normoxic conditions. Whereas U87-MG exhibited a strong aerobic expression, U251 and U373 displayed moderate and GaMG very weak normoxic CA9 protein bands. Aza. as well as SU.D2 displayed inhibitory characteristics to hypoxia induced CA9 expression in the four GBM cell lines for 24 h of hypoxia (0.1% O 2 ) at concentrations between 3500 and 8000 nM, on both the protein and mRNA level. Parallel experiments using CA9-siRNA confirmed these results. Application of 150–500 nM of the glycolysis inhibitor Chetomin under similar oxygenation conditions led to a sharply reduced expression of both CA IX protein and CA9 mRNA levels, indicating a clear glucose availability involvement for the hypoxic HIF-1α and CA9 expression in GBM cells. Hypoxia significantly influences the behaviour of human tumour cells by activation of genes involved in the adaptation to hypoxic stress. The main objective in malignant GBM therapy is either to eradicate the tumour or to convert it into a controlled, quiescent chronic disease. Aza., SU.D2, Chetomin or CA9-siRNA possesses functional CA9 inhibitory characteristics when applied against human cancers with hypoxic regions like GBM. They may be used as alternative or in conjunction with other direct inhibitors possessing similar functionality, thereby rendering them as potential optimal tools for the development of an optimized therapy in human brain cancer treatment.

The amount of fluid that may be lost into the soft tissues during hip arthroscopic surgery is unknown. We measured the volumes of irrigation fluid infused, operating time, fluid pressures and volumes of fluid recovered in 36 therapeutic hip arthroscopies. We excluded those where fluid was lost to the floor, leaving 28 patients. The majority were undergoing surgery for the treatment of femoroacetabular impingement. In 5 patients an intra-articular contrast medium was instilled, in order to establish the likely location of any extravasated fluid. The mean operating time was 68 minutes (31 to 120), and the mean infusion pressure was 46 mm Hg (30 to 70). The mean volume of infused fluid was 9677 ml (95% confidence interval (CI) 7715 to 11638) and the mean volume of fluid recovered was 8544 ml (95% CI 6715 to 10373). The mean fluid extravasation loss into the peri-articular tissues was 1132 ml (95% CI 808 ml to 1456 ml). There was a significant correlation between the volume of extravasated fluid and both the length of operation and the volume of infused fluid used. We had no adverse events in our series. During arthroscopic hip surgery more than a litre of irrigation fluid may be extravasated into the soft tissues. In order to reduce problems related to this we attempt to keep operating times low, and maintain intra-operative fluid pressures as low as possible.

The primary objective of this augmental, prospective, uncontrolled phase II multicentre trial was to assess adverse events (AE) associated with malignant glioma resection using 5-aminolevulinic (5-ALA). During accrual, the standard of adjuvant therapy changed to concomitant radiochemotherapy with adjuvant temozolomide (RT/TMZ). Thus, this study also provided a platform for investigating the influence of RT/TMZ on survival in patients with fluorescence-guided resections. Malignant glioma patients, aged 18-75 years and with a Karnofsky performance score (KPS) ≥70%, were eligible. Data were collected on adverse events, KPS, survival and adjuvant therapies. In 243 patients evaluable for safety, 6-week AE incidence was 51.9% (nervous system disorders: 30.0%). Three patients experienced four possibly drug-related AEs. Grade III/IV incidence was 18.9% (nervous system disorders: 10.7%). About 48 h after surgery, AE incidence was 26.3% (9.9% grade III/IV), which was related to overall survival. A total of 219 patients (glioblastoma 206; anaplastic astrocytoma: 13) qualified for efficacy analysis. Median overall survival was 14.1 months (95% CI: 12.0-16.6), but 16.3 (13-19.2) months in 122 glioblastoma patients receiving RT/TMZ compared to 11.9 (9.6-14.1) months in the remaining 84 patients (P = 0.0194). Older patients (≥60 years) had less adjuvant therapies than younger patients. Median survival of older glioblastoma patients with RT/TMZ was also significantly prolonged (16.3; 12.0-17.2 months vs. 11.2; 7.4-14.1, hazard ratio = 0.55; 0.32-0.92). Risks of surgery were similar to past experiences with 5-ALA. Ancillary analyses demonstrated surgical glioblastoma patients, including the elderly, to have derived benefit from RT/TMZ. Thus, older patients should not generally be excluded from accepted therapies (fluorescence-guided resection plus RT/TMZ).

To examine whether the maintenance of elevated magnesium serum concentrations by intravenous administration of magnesium sulfate can reduce the occurrence of cerebral ischemic events after aneurysmal subarachnoid hemorrhage.Prospective, randomized, placebo-controlled study.Neurosurgical intensive care unit of a University hospital.One hundred ten patients were randomized to receive intravenous magnesium sulfate or to serve as controls. Magnesium treatment was started with a bolus of 16 mmol, followed by continuous infusion of 8 mmol/hr. Serum concentrations were measured every 8 hrs, and infusion rates were adjusted to maintain target levels of 2.0-2.5 mmol/L. Intravenous administration was continued for 10 days or until signs of vasospasm had resolved. Thereafter, magnesium was administered orally and tapered over 12 days.Delayed ischemic infarction (primary end point) was assessed by analyzing serial computed tomography scans. Transcranial Doppler sonography and digital subtraction angiography were used to detect vasospasm. Delayed ischemic neurologic deficit was determined by continuous detailed neurologic examinations; clinical outcome after 6 months was assessed using the Glasgow outcome scale. Good outcome was defined as Glasgow outcome scale score 4 and 5.The incidence of delayed ischemic infarction was significantly lower in magnesium-treated patients (22% vs. 51%; p = .002); 34 of 54 magnesium patients and 27 of 53 control patients reached good outcome (p = .209). Delayed ischemic neurologic deficit was nonsignificantly reduced (9 of 54 vs. 15 of 53 patients; p = .149) and transcranial Doppler-detected/angiographic vasospasm was significantly reduced in the magnesium group (36 of 54 vs. 45 of 53 patients; p = .028). Fewer patients with signs of vasospasm had delayed cerebral infarction.These data indicate that high-dose intravenous magnesium can reduce cerebral ischemic events after aneurysmal subarachnoid hemorrhage by attenuating vasospasm and increasing the ischemic tolerance during critical hypoperfusion.

Losses and rearrangements of genetic material on chromosome 6q are frequently found in several human malignancies, including primary central nervous system tumors. We previously used microsatellite analysis of ependymomas to identify frequent deletions in regions 6q15 approximately q16, 6q21 approximately q22.1, and 6q24.3 approximately q25.3. To refine our preliminary analysis of potential prognostic regions, we used a panel of 25 microsatellite markers located between 6q15 and 6qter in 49 pairs of matched normal and tumor specimens from 28 children and 21 adults with ependymoma. Allelic deletions were detected in 34 of 49 patients (69%), and two common regions of deletions (6q24.3 and 6q25.2 approximately q25.3) were identified. A short segment of approximately 0.4 Mb between D6S1612 and D6S363 on 6q25.3, containing the SNX9 and SYNJ2 genes, exhibited the highest number of aberrations (n = 38). Pediatric tumors showed slightly fewer aberrations (64%) than adult tumors (76%) and also predominantly exhibited small interstitial deletions, in contrast to the extensive losses of genetic material in adults. Pediatric anaplastic intracranial (supra- and infratentorial) ependymomas harboring the 6q25.3 deletion (n = 9) showed significantly longer overall survival than did patients of the same group without the aberration (n = 6), independent of the extent of resection (P = 0.013). This supports the identified deletion on 6q25.3 as a candidate favorable prognostic parameter and warrants further investigation.

Glioblastomas (GBM) are the most prevalent type of malignant primary brain tumor in adults. They may manifest de novo or develop from low-grade astrocytomas (LGA) or anaplastic astrocytomas. They are characterized by an aggressive local growth pattern and a marked degree of invasiveness, resulting in poor prognosis. Tumor progression is facilitated by an increased activity of proteolytic enzymes such as matrix metalloproteinases (MMPs). Elevated levels of several MMPs were found in glioblastomas compared to LGA and normal brain (NB). However, data for some MMPs, like MMP-1, are controversially discussed and other MMPs like MMP-11 and MMP-19 have as yet not been analysed in detail. We examined the expression of MMP-1, MMP-9, MMP-11 and MMP-19 in NB, LGA and GBM by semiquantitative RT-PCR, Western blotting and immunohistochemistry and found an enhanced expression of these MMPs in GBM compared to LGA or NB in signal strength and in the percentage of tumors displaying MMP expression. The transition from LGA to GBM was characterized by a shift of pro-MMP-11 to expression of the active enzyme. Therefore, MMP-1, MMP-11 and MMP-19 might be of importance for the development of high-grade astrocytic tumors and may be promising targets for therapy.

Background Mobile 3D fluoroscopes have become increasingly available in neurosurgical operating rooms. In this series, the image quality and value of intraoperative 3D fluoroscopy with intravenous contrast agent for the evaluation of aneurysm occlusion and vessel patency after clip placement was assessed in patients who underwent surgery for intracranial aneurysms. Materials and methods Twelve patients were included in this retrospective analysis. Prior to surgery, a 360° rotational fluoroscopy scan was performed without contrast agent followed by another scan with 50 ml of intravenous iodine contrast agent. The image files of both scans were transferred to an Apple PowerMac® workstation, subtracted and reconstructed using OsiriX® free software. The procedure was repeated after clip placement. Both image sets were compared for assessment of aneurysm occlusion and vessel patency. Results Image acquisition and contrast administration caused no adverse effects. Image quality was sufficient to follow the patency of the vessels distal to the clip. Metal artifacts reduce the assessability of the immediate vicinity of the clip. Precise image subtraction and post-processing can reduce metal artifacts and make the clip-site assessable and depict larger neck-remnants. Conclusion This technique quickly supplies images at adequate quality to evaluate distal vessel patency after aneurysm clipping. Significant aneurysm remnants may be depicted as well. As it does not require visual control of all vessels that are supposed to be evaluated intraoperatively, this technique may be complementary to other intraoperative tools like indocyanine green videoangiography and micro-Doppler, especially for the assessment of larger aneurysms. At the momentary state of this technology, it cannot replace postoperative conventional angiography. However, 3D fluoroscopy and image post-processing are young technologies. Further technical developments are likely to result in improved image quality.

To identify molecular markers of tumor hypoxia and potential therapeutic targets in glioblastoma (GBM), we investigated the hypoxia-related expression of osteopontin (OPN), carbonic anhydrase 9 (CA9), erythropoietin (EPO), vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1alpha (HIF-1alpha) in vitro in human GBM cell lines and in vivo in human tumor samples of GBM, compared to low-grade astrocytoma (LGA).Expression of the hypoxia-induced genes OPN, CA9, EPO, VEGF and HIF-1alpha was analyzed in three GBM cell lines, GaMG, U373 and U251, under in vitro hypoxia (1, 6 or 24h at 5%, 1% or 0.1% O(2)) and in tumor samples from two patient groups with LGA and GBM (n=15 each), at the mRNA level (semiquantitative RT-PCR). Selected conditions and representative tumor samples were also evaluated at the protein level by Western blot.OPN and CA9 mRNA was most consistently upregulated in relation to severity and duration of in vitro hypoxia. In tumor samples, mean expression levels (LGA vs. GBM, normalized to mean expression in normal brain) were 1.71 vs. 4.57 (p0.001) for OPN, 1.11 vs. 3.35 (p0.001) for CA9, 2.79 vs. 5.28 (not significant, n.s.) for Epo, 1.13 vs. 2.0 (p=0.007) for VEGF and 0.97 vs. 0.97 (n.s.) for HIF-1alpha. In tumor samples, GBM showed a particularly strong protein expression of OPN.Among a panel of known hypoxia-inducible genes, OPN and CA9 emerge as most consistently induced by in vitro hypoxia in human GBM cell lines and most specifically expressed in patient GBM tumor tissue, rendering these two genes attractive targets for hypoxia-directed treatment approaches.

Ependymomas are primary tumors of the central nervous system that typically originate from the walls of the cerebral ventricles or from the spinal canal. The pathogenesis of these tumors is poorly understood, and prognostic assessment based on histologic features and clinical parameters is difficult. The aim of this study was to investigate the molecular heterogeneity of ependymomas. We used cDNA microarrays and RT-PCR to examine gene expression in 47 ependymomas. We present results for five comparisons: (1) tumors from children and adults with poor versus favorable outcome, (2) tumors from children with poor versus favorable outcome, (3) tumors with high versus low proliferation indices, (4) subependymomas versus myxopapillary ependymomas, and (5) spinal versus intracranial ependymomas. For patients with an overall survival >10 years after diagnosis, we identified 27 genes associated with favorable prognosis. In contrast, overexpression of BNIP3, MRC1, EPHB3, GLIS3, CDK4, COL4A2, EBP, NRCAM, and CCNA1 genes in tumors with high proliferation indices was associated with a poor outcome. Thirty genes, including ETV6, YWHAE, TOP2A, TLR2, IRAK1, TIA1, and UFD1L were found to be highly expressed in subependymomas but not myxopapillary ependymomas. Also, 30 genes were differentially expressed in spinal versus intracranial ependymomas. There was no relationship between expression profiles and tumor grade, patient age, and patient gender. Our results provide insight into specific molecular events underlying ependymoma tumorigenesis and may contribute to more accurate diagnosis and prediction of clinical outcome.

In order to investigate the impact of signalling proteins on the phenotype and malignant behavior of glioblastoma cells, we optimized the transfection procedure of human glioblastoma cell lines U251, U373, GaMG and of primary cells obtained from a patient's tumor using nucleofection technology in conjunction with plasmid pmaxGFP. We describe the optimization procedure, show that a high percentage of the cells can be transfected and that nucleofection does not cause phenotypic alterations of the cells. Therefore, we conclude that nucleofection is a highly efficient tool to deliver plasmids for transient protein overexpression and siRNA for specific protein knock-down to different glioblastoma cell lines or primary cells.

Coil fracture represents a serious device-related complication during coil embolisation of intracranial aneurysms. If the coil cannot be retrieved completely, the loose end floating in the parent vessel can prolapse into the distal part of the vessel and may cause occlusion and brain infarction. We present a new technique in which the loose end of the fractured coil is fixed with a stent at the proximal parent vessel wall. Herniation of the loose coil end to the distal part of the vessel with potential vessel occlusion is therefore prevented. This procedure was technically feasible in all cases and no clinical complications were encountered. We suggest this new technique as a treatment option in cases of fractured coils.

Tumour endothelial markers (TEMs) are a newly discovered family of endothelial markers associated with tumour specific angiogenesis. This study sought to examine the levels of expression for TEMs in human breast cancer. Breast cancer tissues (n = 120) together with normal background tissues (n = 33) were obtained after surgery. RNA was extracted from frozen sections for gene amplification. The expression of TEMs was assessed using RT-PCR and the quantity of their transcripts was determined using real-time-quantitative PCR (Q-RT-PCR). TEM-7R (P = 0.05) and TEM-8 (P < 0.01) were significantly raised in breast cancer tissues compared with the levels detected in normal background tissues. After a median follow-up of 72.2 months it was found that patients who had recurrent disease and/or who had died from breast cancer had a significantly (P < 0.05) elevated level of TEM-1 compared to those patients who were disease free. In addition, elevated levels of TEM-4, TEM-5, TEM-6, TEM-7 and TEM-7R were also raised in breast cancer tissues. Patients who had developed nodal involvement exhibited significantly (P < 0.05) high levels of TEM-1 and TEM-7R compared to patients who were node negative. Furthermore, the levels of TEMs did not correlate with tumour or histological grade. We conclude that elevated levels of TEM-1, TEM-7R and TEM-8 (but not TEM-2, 4, 5, 6 and 7) are associated with either nodal involvement, and/or disease progression, and may therefore, have a prognostic value in breast cancer.

The aim of this study was to compare the outcome of hip arthroscopy for femoroacetabular impingement (FAI) between athletes and non-athletes.The authors prospectively collected data on 122 patients, the largest comparative series reported, who underwent hip arthroscopy for FAI. Of these, 80 actively participated in sporting activities (athletes), while 42 did not (non-athletes). Patients were asked to complete questionnaires for the modified Harris hip score (MHHS), non-arthritic hip score (NAHS), patient satisfaction on a visual analogue scale (VAS). This was collected immediately before surgery, and at 6 weeks, 6 months and 1 year after the procedure. The responses to the MHHS questionnaire were used to calculate the quality-of-life (QoL) score using the Rosser index matrix.A significant improvement in the MHHS, NAHS and QoL was observed at 6 weeks, 6 months and 1 year after surgery (p0.001). The 6-week MHHS (p=0.01) and NAHS (p=0.04) for the athletes were significantly better as compared with non-athletes. However, the 6-month and 1-year MHHS, NAHS and QoL scores were statistically similar for both groups.In this large, prospective series of patients we have demonstrated the positive impact of arthroscopic surgery for FAI in both the athletic and non-athletic population. Arthroscopic management of FAI is thus not the sole domain of the athletic patient. Non-athletes can do just as well.

Exophytic glioblastoma arising from the cerebellar tonsil is an extremely rare variant within the possible anatomical presentations of the glioblastoma multiforme (GBM). We report the case of a 55-year-old woman who presented with a tumor located at the cranio-cervical junction with compression of the medulla oblongata and consecutive hydrocephalus. Due to the radiological presentation, the first tentative diagnosis was a meningioma. The tumor was microsurgically removed. Histopathological examination of the tumor revealed a GBM WHO IV. The patient underwent a postoperative percutaneous radiotherapy and concomitant chemotherapy with temozolomide. GBM should be also considered in the differential diagnosis of cerebellar tumors.

Os acromiale is an unfused epiphysis of the anterior part of the acromion occurring in approximately 8% of the population. Infection of this joint has not been previously described in the literature. We report such a case in a 59-year-old woman presenting with shoulder pain. A high index of clinical suspicion, with early imaging of the shoulder leading to prompt and definitive diagnosis, can lead to appropriate treatment and produce a favorable outcome.

The most appropriate surgical technique for posterior fossa decompression in Chiari malformation (CM) remains a matter of debate. Intraoperative electrophysiological studies during posterior fossa decompression of Type I CM (CM-I) aim to shed light on the entity's pathomechanism as well as on the ideal extent of decompression. The existing reports on this issue state that significant improvement in conduction occurs after craniotomy in all cases, but additional durotomy contributes a further improvement in only a minority of cases. This implies that craniotomy alone might suffice for clinical improvement without the need of duraplasty or even subarachnoid manipulation at the level of the craniocervical junction. In contrast to published data, the authors describe the case of a 32-year-old woman who underwent surgery for CM associated with extensive cervicothoracic syringomyelia and whose intraoperative somatosensory evoked potentials (SSEPs) did not notably improve after craniotomy or following durotomy; rather, they only improved after opening of the fourth ventricle and restoration of CSF flow through the foramen of Magendie. Postoperatively, the patient recovered completely from her preoperative neurological deficits. To the authors' knowledge, this is the first report of significant SSEP recovery after opening the fourth ventricle in the decompression of a CM-I. The electrophysiological and operative techniques are described in detail and the findings are discussed in the light of available literature. The authors conclude that there might be a subset of CM-I patients who require subarachnoid dissection at the level of the craniocervical junction to benefit clinically. Prospective studies with detailed electrophysiological analyses seem warranted to answer the question regarding the best surgical approach in CM-I decompression.

The emergence of an association between gadolinium-based contrast agents (GBCA) and the rare condition nephrogenic systemic fibrosis (NSF) led to a warning in 2006 from the Food and Drug Administration (FDA) restricting the use of the GBCAs to patients with an estimated glomerular filtration rate of30 mL/min/1.73m(2) . We discuss our experience with a post-FDA restriction presentation of NSF and subsequent patient death in which the prolonged lead-time of ∼5.5 years led to challenges in ensuring a secure diagnosis of NSF and establishing risk exposures. Accurate contemporary records of contrast administration and clinical factors alongside clinical and pathological expertise ensured that we were able to confidently diagnose NSF, despite the length of lead time and confounding factors.

Background Glioblastoma multiforme located in the posterior fossa is extremely rare with a frequency up to 3.4%. Compared with glioblastoma of the hemispheres the prognosis of infratentorial glioblastoma seems to be slightly better. Absence of brainstem invasion and low expression rates of epidermal growth factor receptor are described as factors for long-time survival due to the higher radiosensitivity of these tumors. Case presentation In this case study, we report a German female patient with an exophytic glioblastoma multiforme arising from the cerebellar tonsil and a secondary spinal manifestation. Furthermore, the tumor showed no O (6)-Methylguanine-DNA methyltransferase promotor-hypermethylation and no isocitrate dehydrogenase 1 mutations. All these signs are accompanied by significantly shorter median overall survival. A long-term tumor control of the spinal metastases was achieved by a combined temozolomide/bevacizumab and irradiation therapy, as part of a standard care administered by the treating physician team. Conclusion To our knowledge this is the first published case of a combined cerebellar exophytic glioblastoma with a subsequent solid spinal manifestation. Furthermore this case demonstrates a benefit undergoing this special adjuvant therapy regime in terms of overall survival. Due to the limited overall prognosis of the disease, spinal manifestations of glioma are rarely clinically relevant. The results of our instructive case, however, with a positive effect on both life quality and survival warrant treating future patients in the frame of a prospective clinical study.

BACKGROUND By detection of the Ki-1 antigen, Stein (1985) defined a new entity of anaplastic large cell lymphoma [24]. Apart from our case, only four further cases of Ki-1 positive primary central nervous system lymphoma (PCNSL) have been reported in the literature to date. CASE REPORT A 63-year-old man presented with two frontal and parietal mass lesions and one ring lesion on computed tomography scan. Clinically, no evidence of brain metastases or abscesses could be found. Immunohistochemical investigations of biopsy specimens revealed a large cell anaplastic T-cell lymphoma positive to Ki-1 antigen. In spite of all therapeutic efforts, the patient died less than 3 months after the onset of symptoms. DISCUSSION In all cases the clinical course was very rapid, suggesting that Ki-1 positive PCNSL might form an aggressive subtype of lymphomas. Since the radiologic appearance was atypical and clinical diagnosis was not possible, diagnostic biopsy for immunohistochemical diagnosis should be performed.

Study Design. Ten subjects (seven with neurogenic claudication and three control subjects) underwent examination of lower limb muscle blood flow before and after exercise using positron emission tomography. Objectives. To investigate the hypothesis that lower limb muscle ischemia was the origin of symptoms in neurogenic claudication. Background. Patients with neurogenic claudication secondary to spinal stenosis experience lower limb discomfort after exercise similar to that of ischemic claudication. However, they do not have clinical evidence of peripheral vascular disease. The authors postulated that the lower limb discomfort in patients with neurogenic claudication may arise from muscle ischemia due to inadequate dilatation of arterioles in response to exercise, this itself arising secondary to sympathetic dysfunction due to spinal stenosis. Method. Using O 15 -labeled water and positron emission tomography measured thigh and leg muscle blood flow response to exercise bilaterally in seven patients with unilateral neurogenic claudication and three constrol subjects were measured. Results. The average values obtained for mid-thigh and mid-calf muscle perfusion at rest were 2.57 ml/min/100 g tissue (2.23-3.90) and 2.39 ml/ml/100 g tissue (2.03-3.46), respectively. The average values obtained from mid-thigh and mid-calf perfusion after exercise were 4.41 ml/min/100 g tissue (2.8-6.0) and 4.87 ml/min/100 g (2.2-11.7). We found no difference in muscle perfusion between symptomatic and asymptomatic limbs in this group of patients. Conclusions. These studies suggest that muscle ischemia is not the origin is not the origin of symptoms in most patients with neurogenic claudication

INTRODUCTION The aim of this study was to look at the different claims made about hip resurfacing arthroplasty in the popular UK print media and how this relates to findings in the scientific literature. METHODS A review of UK popular print media from January 1992 to June 2011 was performed using the Lexis® Library online news database. Only articles discussing the clinical results of hip resurfacing arthroplasty were included. After excluding duplicates, 49 newspaper articles were found suitable for this study. The main outcome measure was the claims made in popular UK print media about hip resurfacing. These were compared with the scientific publication. We reviewed the trend of use of hip resurfacing prostheses during the same period as reported in the National Joint Registry. RESULTS A disparity was found between the claims in the newspapers and published scientific literature. The initial newspaper articles highlighted only the positive aspects of hip resurfacing arthroplasty, without definitive contemporary evidence backing the claims. Most of these claims were refuted by future scientific publications. The initial positive media reports coincided with an increase in the use of hip resurfacing but the decline coincided with negative reports in the scientific literature. CONCLUSIONS The trend of the newspaper articles and that of the number of hip resurfacing prostheses implanted suggests that the media may have been partly responsible for the increased use of this prosthesis. The subsequent decrease was initiated by the scientific literature.

The benefit of arthroscopy of the hip in the treatment of femoroacetabular impingement (FAI) in terms of quality of life (QoL) has not been reported. We prospectively collected data on 612 patients (257 women (42%) and 355 men (58%)) with a mean age at the time of surgery of 36.7 years (14 to 75) who underwent arthroscopy of the hip for FAI under the care of a single surgeon. The minimum follow-up was one year (mean 3.2 years (1 to 7)). The responses to the modified Harris hip score were translated using the Rosser Index Matrix in order to provide a QoL score. The mean QoL score increased from 0.946 (-1.486 to 0.995) to 0.974 (0.7 to 1) at one year after surgery (p < 0.001). The mean QoL score in men was significantly higher than in women, both before and one year after surgery (both p < 0.001). However, the mean change in the QoL score was not statistically different between men and women (0.02 (-0.21 to 0.27) and 0.04 (-0.16 to 0.87), respectively; p = 0.12). Linear regression analysis revealed that the significant predictors of a change in QoL score were pre-operative QoL score (p < 0.001) and gender (p = 0.04). The lower the pre-operative score, the higher the gain in QoL post-operatively (ρ = -0.66; p < 0.001). One year after surgery the QoL scores in the 612 patients had improved in 469 (76.6%), remained unchanged in 88 (14.4%) and had deteriorated in 55 (9.0%).

We present a CLIPPER program for the calculation and graphical representation of minimal spanning trees (MST) which is available on request on diskette from the authors. The MST are a useful parameter for structural cluster detection. They can be applied to grading problems in tumour biology. We present and discuss the applicability of MST by an example from the field of astrocytoma grading.

We describe one- to three-year results of a novel use of fibrin glue in the treatment of cartilage damage by arthroscopy in the hip. This technique uses the microfracture technique and fibrin adhesive to bond delaminated articular cartilage to the underlying subchondral bone. This is generally performed in conjunction with treatment of underlying pathology such as femoroacetabular impingement.Patients were assessed using the modified Harris Hip Score (MHHS) pre- and post-operatively, and statistical significance determined by Student's t-test. We report the mid-term results of 43 patients with femoroacetabular impingement who have undergone this technique for re-attachment of delaminated chondral flaps.There was a statistically significant improvement in MHHS at a mean of 28 months (16 to 42 months) after surgery (p

A novel technique is presented that addresses the issue of how to apply internal standard (IS) to dried matrix spot (DMS) samples that allows the IS to integrate with the sample prior to extraction. The TouchSpray, a piezo electric spray system, from The Technology Partnership (TTP), was used to apply methanol containing IS to dried blood spot (DBS) samples. It is demonstrated that this method of IS application has the potential to work in practice, for use in quantitative determination of circulating exposures of pharmaceuticals in toxicokinetic and pharmacokinetic studies. Three different methods of IS application were compared: addition of IS to control blood prior to DBS sample preparation (control 1), incorporation into extraction solvent (control 2), and the novel use of TouchSpray technology (test). It is demonstrated that there was no significant difference in accuracy and precision data using these three techniques obtained using both manual extraction and direct elution.

Discovery of an association between gadolinium-based contrast agents (GBCAs) and nephrogenic systemic fibrosis (NSF) has led to less use of GBCA-enhanced magnetic resonance imaging in dialysis patients and patients with severe renal failure at risk of NSF, and the virtual elimination of new cases of NSF. But shifting patients with renal failure to alternative imaging methods may subject patients to other risks (e.g., ionizing radiation or iodinated contrast). This review paper examines 370 NSF cases reported in 98 articles to analyze NSF risk factors. Eliminating multiple risk factors by limiting GBCA dose to a maximum of 0.1 mmol/kg, dialyzing patients undergoing dialysis quickly following GBCA administration, delaying GBCA in acute renal failure until after renal function returns or dialysis is initiated, and avoiding nonionic linear GBCA in patients with renal failure especially when there are proinflammatory conditions may substantially reduce the risk of NSF.

The goal of this study was to evaluate accelerated radiotherapy with and without temozolomide (TMZ) for glioblastoma multiforme (GBM). This retrospective analysis evaluated 86 patients with histologically proven GBM who were treated with accelerated radiotherapy of 1.8 Gy twice daily to a total dose of 54 Gy within 3 weeks. Median age was 62 years and median Karnofsky index was 90. A total of 41 patients received radiotherapy only from 2002–2005 and 45 patients were treated with TMZ concomitantly and after radiotherapy from 2005–2007. Median overall survival (OS) was 12.5 months and 2-year OS was 15.4%. Patient characteristics were well balanced between the two groups except for better performance status (p = 0.05) and higher frequency of retreatment for the first recurrence (p = 0.02) in the TMZ group. Age at diagnosis (HR 2.83) and treatment with TMZ (HR 0.60) were correlated with OS in the multivariate analysis: treatment with and without TMZ resulted in median OS of 16 months and 11.3 months, respectively. Hematological toxicity grade > II was observed in 2/45 patients and 5/37 patients during simultaneous radiochemotherapy and adjuvant TMZ. TMZ added to accelerated radiotherapy for GBM resulted in prolonged overall survival with low rates of severe hematological toxicity.

Glioblastoma multiforme (GBM) is the most prevalent, highly malignant, invasive and difficult-to-treat primary brain tumor in adults. At the genetic level, it is characterized by a high degree of chromosomal instability and aneuploidy. It has been shown that defects in the mitotic spindle checkpoint could lead to the development of aneuploidy as well as tumorigenesis. Additional proteins regulating sister chromatid cohesion could also be involved in maintaining the fidelity of chromosome segregation. One such protein is the precocious dissociation of sisters 5A (Pds5A), also known as sister chromatid cohesion protein 112. It is a nuclear protein, expressed from the S right through to the mitotic phase. It is highly conserved from yeast to man and plays a role in the establishment, maintenance and dissolution of sister chromatid cohesion. The mutation of Pds5A orthologs in lower organisms results in chromosome missegregation, aneuploidy and DNA repair defects. It is considered that such defects can cause either cell death or contribute to the development of cancer cells. Indeed, altered expression levels of Pds5A have been observed in tumors of the breast, kidney, oesophagus, stomach, liver and colon. Malignant gliomas, however, have not been analysed so far. Herein, we report on the cloning of Rattus norvegicus Pds5A and on the analysis of its expression pattern in rat tissue. We also show that Pds5A is significantly overexpressed at both the mRNA and protein level and that this overexpression correlates positively with the WHO grade of human gliomas. However, functional assays show that the siRNA-mediated knockdown of Pds5A affects sister chromatid cohesion but does not influence mitotic checkpoint function or the proliferation and survival of GBM cells. Although the mechanism by which Pds5A functions in GBM cells remains unclear, its overexpression in high grade gliomas implies that it could play a pivotal role during the development and progression of astrocytic tumors.

Trigeminal neuralgia in Chiari's type I malformation is rare and remains a therapeutic challenge. We report a case of bilateral trigeminal neuralgia in Chiari's type I malformation. This case demonstrates that microvascular decompression can be an effective treatment strategy for this complex pathology.

The inferior colliculus (IC) is an alternative site for electrode placement in neural deafness due to its surgical accessibility and its well-known tonotopic stratification. In patients where tumor surgery has already occurred and the cerebellopontine angle contains scar tissue or tumor-remnants, midline and paramedian supracerebellar approaches are alternative routes. They are often avoided due to concerns regarding the venous drainage of the cerebellum, the electrode trajectory and the course of the electrode cable. We studied these surgical routes in five neuronavigated fixed cadaveric specimens. For paramedian and midline approaches, the transverse sinus was exposed 5.8 mm on average. A mean of 1.6 cerebellar veins, with an average diameter of 2.0 mm, draining to the tentorium were transected to reach the tentorial notch. Only 0.4 arterial branches were met. We conclude that the supracerebellar midline and paramedian approaches provide a good exposure of the IC and offer safe and viable alternative routes to the IC. Additionally, they provide a wider angle of action for optimal electrode placement.

Rasmussen encephalitis (RE) is a rare neurological disorder of childhood characterized by uni-hemispheric inflammation, progressive neurological deficits and intractable focal epilepsy. Destruction of neurons and astrocytes by cytotoxic CD8 T cells has been proposed as a pathogenic mechanism underlying this enigmatic disorder. We tested this hypothesis by analysing the clonal composition and T-cell receptor (TCR) repertoire of CD4+ and CD8+ T cells using complementarity determining region 3 (CDR3) spectratyping from peripheral blood and corresponding CNS specimens. Severe perturbations of the TCR repertoire were found in brain infiltrates from all specimens (n = 5). Clonal expansions, as evidenced by peripheral blood analysis (n = 14), belonged to the CD8+ T-cell subset, while CD4+ cells showed normal distributions. Some of those expansions were analysed in the respective CNS specimens by histochemistry. The stainings showed Vbeta specific T cells containing the cytotoxic molecule granzyme B and lying in close appositions to NeuN+ neurons and GFAP+ astrocytes. Analysis of corresponding CNS/blood specimens revealed overlapping but also CNS-restricted expansions of certain TCR clonotypes suggesting expansions of T cells within the target organ itself. Longitudinal analysis of peripheral blood samples (n = 5) demonstrated dominance but also longitudinal persistence of specific CD8 T-cell clones over time. The Vbeta/Jbeta usage, length of the CDR3, and biochemical characteristics of the CDR3 amino acids suggested high similarities putatively related to common driving antigen(s) without shared clones. Taken together, our data strongly support the hypothesis of an antigen-driven MHC class-I restricted, CD8+ T cell-mediated attack against neurons and astrocytes in the CNS dominating the pathogenesis in RE.