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During the development of new navigation systems, the ergonomic aspects of the accompanying software are seldom taken into account. The VN system is a navigation system working with real and previously stored neuroendoscopic images. The latter enable the module to execute virtual back movement, e.g. in case of bleeding. Several other modules are offered. The aim of the study was the ergonomic analysis of different modules and their learning curves in cadaveric heads. The endoscope was navigated by the neurosurgeon while another person operated the computer. A total of 128 experiments were performed with two software versions. When the landmark tracking module was used, a real learning curve could be observed. By contrast, testing the measurement module did not produce a learning curve. A significant reduction of the time required by the three modules investigated could be observed with software version 2. The module for virtual back movement works best with a minimum time of 20 s for image storage. During machine-human interactions ergonomic software use is important, especially if operative procedures are performed.

Vertebralisdissektionen konnen traumatisch, spontan oder iatrogen verursacht werden. Wahrend spontane Vertebralisdissektionen haufiger sind, finden sich in der Literatur Einzelfallberichte von traumatischen Vertebralisdissektionen. Gerade bei polytraumatisierten Patienten ist die fruhzeitige diagnostische Erkennung schwierig, und die geschilderten Beschwerden des Patienten konnen leicht als Folge der Polytraumatisierung verkannt werden. Im Gegensatz zu den Vertebralisdissektionen stehen die traumatischen Ursachen der Atiopathogenese von Armplexuslasionen an erster Stelle. Trotz ihrer atiopathogenetischen Gemeinsamkeiten wurde nach Kenntnisstand der Autoren in der Literatur bisher noch keine Kombination beider Verletzungen beim traumatisierten Patienten beschrieben.

Severe acute respiratory syndrome (SARS) is caused by the SARS coronavirus (SCV). The disease appeared in the Guandong province of southern China in 2002. The epidemic affected > 8422 patients and caused 908 deaths in 29 countries on 5 continents. Several treatment modalities were tried with limited success to treat SARS and a variety of experimental drugs are under development. Type I interferons (IFNs-alpha/beta) were suggested as potential candidates to treat SARS. Several animal and human coronaviruses, including SCV, were shown to be sensitive to IFNs both in vitro and in vivo. A pilot clinical report showed effectiveness of IFN-alpha for the treatment of SARS patients. This review summarises antiviral activities of IFNs with special regard to SARS, and reviews the published clinical and experimental data describing the use of IFNs for SARS.

Recently, the term oncomodulation has been proposed to express the ability of human cytomegalovirus (HCMV) to modify tumor cell biology, a phenomenon that is independent from transformation. Because past studies have failed to show that HCMV can transform normal human cells, HCMV has not been regarded as an oncogenic tumor virus. However, recent investigations have revealed a high frequency of HCMV in tumor cells of malignancies such as colon cancer, malignant glioma, prostatic intraepithelial neoplasia, and carcinoma. Data from experiments with HCMV-infected tumor cell lines have highlighted the oncomodulatory potential of HCMV and provided important insights into the patho-mechanisms associated with aberrant signaling pathways and transcription factor and/or tumor suppressor function of the host cell.

Cardiac surgery with cardiopulmonary bypass (CPB) is associated with neutrophil activation, inflammation, and consecutive edema. The impairment of endothelial junction molecules, and thus, hyperpermeability elicited by the interaction of activated neutrophils with endothelial cells may be important in this regard. Cocultures with human endothelial cells and neutrophils from 10 cardiac surgery patients with CPB were used to evaluate the role of neutrophils in modifications of the endothelial zonula adherens molecules VE-cadherin and beta-catenin. Laser scan microscopic analyses showed that neutrophils, which were isolated after the beginning of CPB, significantly impaired intracellular redistribution of endothelial beta-catenin with regard to membrane association (p.0002) and staining pattern (p.0001). VE-cadherin localization was not found to be significantly modified. Western blots with total cell extracts showed that amounts of beta-catenin did not vary significantly after co-culture with activated neutrophils. Activated neutrophils during cardiac surgery with CPB may induce endothelial dysfunction by impairing beta-catenin localization and thus contribute to endothelial hyperpermeability.

Brain abscesses are life-threatening and sometimes difficult to detect. A brain abscess after placement, manipulation of a bone anchored hearing aid, or a periauricular implant for fixation of an ear prosthesis has never been reported in the literature.A 42-year-old man suffered from a right-sided temporodorsal brain abscess after change of a bone anchored hearing aid abutment. The fixture itself had been inserted 8 years before without any complications in the peri- or postoperative period. A CT-guided puncture of the abscess could be performed via the screw-hole in the temporal bone after removal of the fixture, and the patient was treated with antibiotics.The outcome of the procedure was good without neurologic deficits for the patient.The insertion of periauricular screw implants bears the risk of meningeal lesions as well as a small risk of purulent intracranial and intracerebral complications perioperatively or in the context of later manipulations. Minimally invasive therapy of such brain abscesses can be performed by removal of the foreign body, CT-guided puncture, and antibiotic medication.

Cardiac surgery with cardiopulmonary bypass (CPB) results in transient cerebral swelling in most patients. Cognitive decline occurs in 24-57% of patients and 2-5% experience stroke. Serum levels of S-100B, a potential marker of increased blood-brain barrier permeability, increase during and early after surgery. The authors studied the effects of the novel Na /H exchange inhibitor cariporide (HOE642) on postoperative serum levels of S-100B and neuron-specific enolase (NSE) in 53 patients at high risk undergoing coronary artery bypass grafting. Patients were randomly assigned to one of four groups: I, placebo; II, 20 mg cariporide; III, 80 mg cariporide; IV, 120 mg cariporide). In addition, the leukocyte activation marker myeloperoxidase (MPO) and malondialdehyde (MDA), a marker for lipid peroxidation, were evaluated by enzyme-linked immunoassay. Postoperatively, five patients experienced transient ischemic attack or stroke. S-100B levels increased from 0.43 microg/l +/- 0.33 before operation to 2.27 microg/l +/- 0.69 1 hour after surgery in the placebo group. Preoperative S-100B levels in the HOE642 groups did not differ from the placebo group whereas, 1 hour after surgery, levels were significantly lower in groups II, III, and IV (1.63 microg/l +/- 0.2, 1.27 microg/l +/- 0.27, and 0.90 microg/l +/- 0.21, respectively). NSE, MPO, and MDA serum levels did not differ among groups. These findings may stimulate larger clinical studies to examine the effects of HOE642 on cerebral swelling and neurologic/cognitive outcome of cardiac surgery with CPB.

Selection of an optimal treatment plan requires the comparison of dose distributions and dose-volume histograms (DVH) of all plan variants calculated for the patient. Each treatment plan consists generally of 30 to 40 CT slices, making the comparison difficult and time consuming. The present study proposes an objective index that takes into account both physical and biological criteria for the evaluation of the dose distribution. The DHV-based evaluation index can be calculated according to the following four criteria: ICRU conformity (review of the differences between the dose in the planning target volume and the ICRU recommendations); mean dose and dose homogeneity of the planning target volume; the product of tumour complication probability (TCP) and normal tissue complication probability (NTCP); and finally a criterion that takes into account the dose load of non-segmented tissue portions within the CT slice. The application of the objective index is demonstrated for two different clinical cases (esophagus and breast carcinoma). During the evaluation period, the objective index showed a good correlation between the doctor's decision and the proposed objective index. Thus, the objective index is suitable for a computer-based evaluation of treatment plans.

Dear Editor, We report the case of a 44-year-old female patient with lumbo-ischialgic pain projecting to dermatomes S1. Conservative treatment was unsuccessful and the pain progressed until the patient was unable to walk. After lumbar computed tomography (CT) evaluation, a radicular compression due to listhesis could be seen in the level L5/S1 (Meyerding Grade I, Fig. 1a). Radicular decompression and screw fixation from L5 to S1 followed. The postoperative CT shows good screw position and dural decompression (Fig. 1b). At this point it is important to mention that the patient had allergies against sodium thiosulphate (dental products), 1,3-diphenylguanidine (rubber) and nickel (II) sulphate. No titanium allergy. Immediately post-surgery, the patient still complained of lumbo-ischialgic pain with a 7/10 visual analogue scale (VAS) score. Because of pain, ambulation was impossible (despite good postoperative results on CT). Inspection of the wound showed oedema, redness and hyperthermia resembling the clinical signs of wound infection. After microbiological screening (Staphylococcus epidermidis, Streptococcus oralis, Streptococcus faecalis and Staphylococcus haemoliticus positive), we started antibiotic treatment even in absence of leucocytosis or increased C-reactive protein. The pain persisted and a lumbar magnetic resonance imaging (MRI) 2 weeks post-surgery failed to show signs of post-operative infection. Irrespective of absence of inflammatory proteins in the serum and/or leucocytosis and under antibiotic treatment, there was putrid wound excretion. Surgical wound debridment followed. Intraoperativelly there was no dislocation of the screws. There were no signs of infection under the skin (i.e. epidural or lumbar bone). After wound-debridment there was still no improvement of pain (VAS 6/10). Creactive protein was normal. Because of persistence of symptoms, another lumbar CT followed 7 weeks postsurgery. No signs of screw dislocation were seen, but at this time there was subcutaneous air identifiable (subcutaneous infection?). MRI and serum failed to show infection. In a second wound debridment, granulation tissue was removed epidurally. The whole time the patient received antibiotic treatment. After two wound revisions we performed an epicutaneus allergy test. A titan screw like the ones used for fixation in the patient’s case was adhered for 48 h on the patient’s upper arm. After 48 h the patient exhibited an allergic reaction of the type IV (allergic contact dermatitis) (Fig. 2). Steel and PEEK cage did not resemble allergic reactions on the patient’s skin. In a third revision we changed the titanium screws with steel screws and a PEEK cage was placed in the intervertebral space L5/S1. Histopathologically, fat and muscle tissue from the wound showed lymphocytic inflammation and chronic inflammatory infiltrates. Immediately after the replacement of the titanium screws the patient showed an improvement of her symptoms (VAS 1/10), and could be discharged with minimal postoperative pain. In the MELISA (Memory Lymphocyte Immunostimulation Assay) test and the lymphocyte transformation test, no Rashad El Habony and Yucel Binay contributed equally

The treatment of meningiomas is still at the borderline of two or even three disciplines. Surgery, radiation and interventional neuroradiology. Even when it seems confusing, reviewing the literature allows us to draw a clear line between the therapeutic modalities. There are cases where surgery is the first line treatment and others where radiation should be first line and again others where pre-operative embolization, surgery and postsurgical radiation are the treatment options of choice. In the present short review we present four cases of different meningiomas treated surgically in our department and we review the literature to provide a flow chart, indicating which treatment modality would fit to different meningiomas. Of course the flow chart is based on the present literature and cannot be followed without restrictions and reservations. Randomized multicenter studies will help to clear this field more effectively.

INTRODUCTION: Owing to increasing numbers of decompressive craniectomies in patients with malignant middle cerebral artery infarction, cranioplastic surgery becomes more relevant. However, the current literature mainly consists of retrospective single-centre (evidence class III) studies. This leads to a wide variability of technical approaches and clinical outcomes. To improve our knowledge about the key elements of cranioplasty, which may help optimising clinical treatment and long-term outcome, a prospective multicentre registry across Germany, Austria and Switzerland will be established. METHODS: All patients undergoing cranioplastic surgery in participating centres will be invited to join the registry. Technical methods, materials, medical history, adverse events and clinical outcome measures, including modified Rankin scale and EQ-5D, will be assessed at several time points. Patients will be accessible to inclusion either at initial decompressive surgery or when cranioplasty is planned. Scheduled monitoring will be carried out at time of inclusion and subsequently at time of discharge, if any readmission is necessary, and at follow-up presentation. Cosmetic results and patient satisfaction will also be assessed. Collected data will be managed and statistically analysed by an independent biometric institute. The primary endpoint will be mortality, need for operative revision and neurological status at 3 months following cranioplasty. ETHICS AND DISSEMINATION: Ethics approval was obtained at all participating centres. The registry will provide reliable prospective evidence on surgical techniques, used materials, adverse events and functional outcome, to optimise patient treatment. We expect this study to give new insights in the treatment of skull defects and to provide a basis for future evidence-based therapy regarding cranioplastic surgery. TRIAL REGISTRATION NUMBER: This trial is indexed in the German Clinical Trials Register (DRKS-ID: DRKS00007931). The Universal Trial Number (UTN) is U1111-1168-7425. peerReviewed

Objective and design: The beneficial effects of leukocyte filtration on the outcome of cardiac surgery with cardiopulmonary bypass (CPB) is probably due to the limitation of pathogenesis mediated by over-stimulated neutrophils. However, the influence of leukocyte filtration on the functional neutrophil activity has not been studied in detail. Therefore, by using different filtration timing strategies we determined neutrophil effector functions before and after the filter passage as well as blood surrogate markers for neutrophil activation.¶Methods: We randomly assigned 80 cardiac surgery patients to four groups (n = 20 each) without (I) and with three different filtration timing strategies (II–IV). As functional end points neutrophil phagocytic activity and oxidative burst upon ex vivo stimulation with E.coli were analyzed from blood of 31 patients whereas polymorphonuclear elastase (PMNE), myeloperoxidase, and malondialdehyde (MDA), a marker for lipid peroxidation was determined in plasma samples from 80 patients. Blood was harvested immediately before and behind the filter (Pall LG6) at different times during CPB.¶Results: We found that none of the filtration strategies either reduced the number of neutrophils capable of eliciting phagocytic activity and oxidative burst or the activity per cell. In contrast, PMNE and MPO levels in peripheral venous blood were found to be significantly increased in groups II–IV compared with group I throughout the entire filtration period in all patients. MDA was not enhanced in the filter groups.¶Conclusions: Our results show that the leukocyte depletion filter in the arterial line of the heart-lung machine failed to limit neutrophil stimulation but rather augmented PMNE plasma levels. We speculate that augmented PMNE and MPO levels mainly stem from neutrophils that are captured within the mesh of the leukocyte filter.

OBJECTIVE: Tumor Treating Fields (TTFields) are a non-invasive, low intensity, intermediate frequency, alternating electric fields serving as anti-mitotic therapy for treatment of patients with newly diagnosed or recurrent glioblastoma multiforme (GBM). Recently, the Phase 3 EF-14 study demonstrated significantly prolonged overall survival in newly diagnosed GBM patients treated with TTFields + Temozolomide (TMZ) compared to TMZ alone. Although the development of hydrocephalus is a rare complication of GBM treatment, the need for a programmable shunt however, could prevent patients from TTFields treatment as the implantation of a programmable valve is a contraindication. In our multicentric observational cohort, we assessed patients requiring programmable valves during concomitant TTFields treatment with the Optune® System, for safety and feasibility. METHODS: We observed six patients (male=4, female=2) of median age 47.3 years (range 26-59 years) with newly diagnosed or recurrent GBM who had received programmable shunt valves due to different indications such as hydrocephalus, CSF fistula or partial obstruction of ventricles. Shunt indications and valve types implanted differed throughout different neurosurgical departments, according to local standards of care. All patients received antimitogenic treatment with Optune; the shunt valve was radiographically assessed at predefined time points of clinical practice after the initiation of TTFields treatment. Patients were treated at 4 different centers in Germany and Austria, respectively. RESULTS: All programmable shunt types proved functional while undergoing simultaneous treatment with TTFields. We found no influence of alternating electric fields on shunt valve programming during follow-up. For patients’ safety, shunt programming was assessed meticulously. Further imaging (MRI / CT follow-up) included the assessment of shunt valves, showed no dysfunction or unintended reprogramming. CONCLUSION: Our multicentric observational case series demonstrated safety and feasibility of Optune in patients with programmable shunt valves. Additional studies are needed to validate our observations and assess comparable efficacy of TTFields in patients with the need of programmable shunt valves.

Rapid responses of chloroplast metabolism and adjustments to photosynthetic machinery are of utmost importance for plants’ survival in a fluctuating environment. These changes may be achieved through posttranslational modifications of proteins, which are known to affect the activity, interactions, and localization of proteins. Recent studies have accumulated evidence about the crucial role of a multitude of modifications, including acetylation, methylation, and glycosylation, in the regulation of chloroplast proteins. Both of the Arabidopsis (Arabidopsis thaliana) leaf-type FERREDOXIN-NADP+ OXIDOREDUCTASE (FNR) isoforms, the key enzymes linking the light reactions of photosynthesis to carbon assimilation, exist as two distinct forms with different isoelectric points. We show that both AtFNR isoforms contain multiple alternative amino termini and undergo light-responsive addition of an acetyl group to the α-amino group of the amino-terminal amino acid of proteins, which causes the change in isoelectric point. Both isoforms were also found to contain acetylation of a conserved lysine residue near the active site, while no evidence for in vivo phosphorylation or glycosylation was detected. The dynamic, multilayer regulation of AtFNR exemplifies the complex regulatory network systems controlling chloroplast proteins by a range of posttranslational modifications, which continues to emerge as a novel area within photosynthesis research.

Background: The present study evaluates the effectiveness of an ultrasound (US) practice course based on a sheep brain cadaver. Neurosurgical education is considerably restrained following patient safety objections and work time restrictions. It is therefore of vital importance to offer residents an opportunity to practice certain US techniques in a controlled environment without ethical or legal restrictions. We developed an US training model based on a sheep brain cadaver in order to demonstrate the feasibility of such a model, facilitate crucial anatomic knowledge, and demonstrate a learning curve from it. Methods: Over the course of 2 months from December 2012-January 2013, a total of 13 residents took part in a three part training session, each consisting of 20-30 min of individual US-training and performance evaluation based on a biological phantom. The first cadaver was a physiologic sheep brain. After initial familiarization with the US, the residents performed an US on a second cadaveric brain and tried to find a 0.5 cm big (in diameter) echogenic structure. In a third brain they were asked to identify a cyst (Fogarty catheter filled with water). Results: Thirteen neurosurgical residents participated in the study. After the first training session, the learning curve improved significantly in the second and the third session. The ability to actuate the US device, the time needed to display crucial anatomic landmarks, and to locate the two different artificial masses increased, and respectively decreased remarkably by up to 80%. Conclusion: After 2 months and three training sessions, the handling of the US from the residents was excellent in the operating room. The accuracy and the dexterity in use of the US improved significantly. The participants found the model to be realistic and agreed on the need for further promotion of such courses.

The posterior reversible encephalopathy syndrome (PRES) is a well described entity of white matter pathology. PRES is triggered by numerous different factors such as acute elevated arterial hypertension, immunosupressive therapy, chemotherapy, etc. The case of a 67-year old woman is presented. The patient was treated for breast cancer 10 months ago and because of acute disorientation a magnetic resonance imaging (MRI) was performed. In the MRI biparieto-occipital hyperintense lesions were seen. Brain metastases were suspected. After chemothe - rapy and hypertonia and the typical appearance of the lesions in the MRI, PRES was also suspected. Before initializing the surgery for an open biopsy a follow-up MRI had been performed (2 weeks after initial MRI). In follow-up MRI the lesions disappeared completely proving the diagnosis of PRES. PRES can be misdiagnosed as a tumour and surgery could be mistakenly performed. It’s important to keep the differential diagnosis of PRES in mind when radiologic features of the syndrome are present.

Preface Regulatory issues Sterilization of combination devices Polyelectrolyte monolayers (I) Polyelectrolyte monolayers (II) Surface modifications Three dimensional characterization of immobilized biomolecules Aptamers for biofunctionalization of stents Coating of implants with antibiotics Microneedles and nanopatchesfor vaccination Microchips for antibody binding analyses Biofunctionalized wound dressings Extracorporeal device for trapping circulating tumor cells Outlook

Leukocyte filtration has evolved as an important technique in cardiac surgery with cardiopulmonary bypass to prevent pathogenic effector functions mediated by activated leukocytes. The underlying mechanisms that result in an improvement of laboratory variables as well as clinical outcome are not resolved yet. Moreover, the optimum strategy for the use of current filtration technology has not been systematically evaluated. This paper, therefore, reviews how activated leukocytes may lead to tissue damage, summarizes the known effects of leukocyte filtration on clinical outcome and laboratory parameters, and deals with current experimental and clinical efforts to further limit the pathogenic effects of leukocytes in cardiac surgery.

The human CMV (HCMV) is a persistent virus that may cause severe inflammatory responses especially in immunocompromised hosts. In different cell types, HCMV infection leads to the activation of the pleiotropic transcription factor, NF-κB, which triggers virus replication but also propagates cell-mediated inflammatory mechanisms that largely depend on PG synthesis. We investigated the interactions of HCMV and the NF-κB-dependent PG synthesis pathway in cultures of retinal pigment epithelial (RPE) cells that are known to be infected in HCMV retinitis patients. Unlike in other cell types, HCMV increased neither NF-κB activity nor p65 and p105/50 mRNA levels in RPE cells. Both TNF-α and phorbol ester 12,0-tetradecanoylphorbol 13-acetate (TPA) enhanced NF-κB activity but only TPA increased HCMV replication. Cyclooxygenase-2 expression and PGE2 release was increased by TPA and TNF-α but not by HCMV infection. Stimulatory activity of TPA on HCMV replication was suppressed by protein kinase C inhibitors and inhibitors of p42/44 and p38 mitogen-activated protein kinases but not by NF-κB inhibitors. In conclusion, HCMV circumvents the NF-κB route in favor of the protein kinase C-dependent mitogen-activated protein kinase pathway in RPE cells. This virus/host cell interaction might be a mechanism that promotes HCMV persistence in immune-privileged organs such as the eye.

Studie. In der vorliegenden retrospektiven Studie wurde die plastische Deckung von Schadeldefekten durch praoperativ mittels CAD/CAM hergestellte Titanimplantate in einer klinischen und radiologischen Nachuntersuchung ausgewertet (76 Patienten mit 78 Titanimplantaten, in 19 Kliniken in Deutschland und dem benachbarten Ausland von 1994–1998 nach dieser Methode operiert). Die Patienten konnten in einem standardisierten Fragebogen zur Lebensqualitat Stellung nehmen und uber ihre Einschatzung des Operationsergebnisses berichten.

Improved myocardial protection and cardiopulmonary bypass (CPB) have limited, but not abolished, intraoperative myocardial damage due to surgical reperfusion injury after release of the aortic crossclamp. In this double-blind, randomized study, we evaluated whether short-term leukocyte filtration during reperfusion may further reduce myocardial damage. Thirty-eight patients with coronary artery disease were randomly assigned to CPB with (group I; n = 19) or without leukocyte filtration (group II; n = 19). There was no difference in bypass time or crossclamp time between the groups. No patient in group I required catecholamines, whereas three patients in group II were supported with adrenaline or dobutamine on the first and second postoperative day. In addition, troponin T plasma levels were lower in group I ( p < 0.05), whereas other markers for tissue injury (CK, CK-MB, LDH, S- GOT and S100B) did not differ. In conclusion, leukocyte filtration during reperfusion may further improve CPB by reducing myocardial damage.

Human cytomegalovirus (HCMV) infection is associated with excessive proinflammatory immune responses such as cytokine/chemokine production or upregulation of adhesion molecules on the host cells. It is assumed that these features of HCMV-related immunopathology can not be treated effectively with currently available anti HCMV drugs. In the present study the efficacy of ganciclovir (GCV), foscarnet (PFA), cidofovir (HPMPC), and ISIS 2922, an antisense oligonucleotide complementary to HCMV immediate-early (IE) mRNA, was investigated on HCMV-induced secretion and functional activity of the C-X-C chemokine IL-8 and the expression of the intercellular adhesion molecule-1 (ICAM-1). As compared with mock-infected cells IL-8 production was increased up to 9-fold and ICAM-1 expression up to 4-fold in HCMV-infected fibroblasts. Treatment of infected cells with GCV (40 microM), PFA (200 microM) or HPMPC (2 microM) suppressed completely virus replication as demonstrated by quantification of late (L) antigen expression and infectious virus production. These drugs, however, failed to inhibit IE antigen expression and did not prevent HCMV-induced upregulation of IL-8 and ICAM-1. In contrast, ISIS 2922 (1 microM) suppressed both IE and L antigen expression by 99% and inhibited infectious virus production by 10(4)-fold. Moreover, ISIS 2922 significantly suppressed HCMV-induced upregulation of both IL-8 and ICAM-1 expression on the transcriptional and on the protein level. Our results indicate that ISIS 2922 but not inhibitors of HCMV DNA prevents HCMV-induced upregulation of IL-8 and ICAM-1, both hallmarks of inflammatory processes. Thus, inhibition of HCMV IE expression with ISIS 2922 may be an important strategy for the treatment of HCMV-related immunopathogenesis.

Background. Cyclosporine A (CsA) and tacrolimus prevent proliferation but not transendothelial migration of alloreactive lymphocytes into donor organs. As a result, serious adverse effects, such as nephrotoxicity and neurotoxicity, have been observed under CsA/ tacrolimus therapy. The incorporation of new drugs with infiltration blocking properties might enhance the efficacy of the current immunosuppressive protocol, allowing lower CsA/tacrolimus dosage. Because Ca 2+ plays a critical role in cell-cell interaction, the Ca 2+ -channel blocker verapamil might be a good cany. didate for supporting CsA/tacrolimus-based therap Methods. A T-cell endothelial cell coculture model or immobilized immunoglobulin G globulin chimeras were employed to investigate how S- and R- verapamil interfere with the lymphocytic infiltration process. The expression and arrangement of membranous adhesion receptors and cytoskeletal F-actin filaments were analyzed by fluorometric method in the presence of, verapamil. Results. Both verapamil enantiomers strongly inhibited lymphocyte infiltration. CD4 + and CD8 + T-cells were influenced to a similar extent with regard to horizontal locomotion (CD4 + =CD8 + ), but to a different extent with regard to adhesion and penetration (CD4 + > CD8 + ). Moreover, penetration was blocked to a higher extent than was adhesion. ID 50 -values were 31 μM (CD4 + -adhesion) and 11 μM (CD4 + -penetration). Verapamil reduced P-selectin expression on endothelial cells and effectively down-regulated binding of T-cells to immobilized P-selectin immunoglobulin G globulins (ID 50 =4.4 μM; CD4 + ). A verapamil-induced reduction of intracellular F-actin in T-lymphocytes was proven to be mainly responsible for diminished cell locomotion. Conclusions. The prevention of CD4 + T-cell penetration by verapamil might argue for its use as an adjunct to CsA/tacrolimus-based immunosuppressive therapy.

Lumbar synovial cysts represent a rare condition, they are believed to arise from defects of the joint capsule due to degeneration, trauma, rheumatoid arthritis or spondylosis. The symptom spectrum ranges from neural claudication to neurological deficits. We report the case of a contralateral asynchronous facet joint cyst after surgical resection and review the literature.

Glioneuronal tumors with neuropil-like islands, so called “rosetted glioneuronal tumors” (RGNTs), were reported a few years ago as a new group of mixed glioneuronal neoplasms [5]. The majority of reported cases were located supratentorially in the cerebrum. Apart from their common distinctive neuronal features, cerebral RGNTs contain a predominant glial component of either WHO grade II or III and—though clinical data are still sparse—they seem to behave in a manner similar to astrocytomas of the respective WHO grade. Thus, the 2007 WHO classiWcation does not regard RGNTs as a separate entity but rather as a distinct diVerentiation pattern that may be found in diVerent types of diVuse gliomas.

Background Cytomegalovirus (CMV) infection is associated with acute and chronic allograft rejection. We have recently shown that rat CMV increases portal inflammation and bile duct destruction in a model of rat liver allograft rejection. Desferrioxamine (DFO), an iron chelator and antioxidant, has recently been demonstrated to have antiviral as well as immunomodulatory effects in vitro. We therefore investigated whether DFO inhibits (a) CMV infection and (b) graft destruction in our rat model. Method One day after liver transplantation, PVG (RT1c) into BN(RT1n), the rats were infected with rat CMV (RCMV, Maastricht strain; 10(5) plaque-forming units i.p.). The effects of 100 mg/kg body weight and 200 mg/kg body weight DFO were examined. Results In the untreated group, the grafts were uniformly RCMV culture-positive. In the group receiving 200 mg/kg DFO, RCMV replication was effectively inhibited. Inflammatory response in the graft, and especially the number of macrophages, was significantly reduced by DFO. Portal inflammation and bile duct destruction were also significantly reduced. In the untreated group, the bile duct epithelial cells were found to be strongly positive for tumor necrosis factor-alpha and this expression was clearly decreased by DFO. In addition, DFO significantly inhibited vascular cell adhesion molecule-1 expression on sinusoidal endothelial cells. Conclusions Our in vivo transplant study strongly supports the inhibitory effects of metal chelators on CMV infection and their possible usefulness in the treatment of CMV-induced pathogenic changes.

Thrombospondin-1 (TSP-1) is a potent inhibitor of angiogenesis. It has been shown that promoter sequences of the TSP-1 gene can be transactivated by the wild-type tumor suppressor protein p53. As human cytomegalovirus (HCMV) infection inactivates wild-type p53 of various cell types, we investigated whether HCMV infection is associated with reduced TSP-1 production. We found, in conjunction with accumulated p53, that TSP-1 mRNA and protein expression was significantly reduced in HCMV-infected cultured human fibroblasts. To determine whether the observed TSP-1 suppression depends on p53 inactivation, the p53-defective astrocytoma cell line U373MG was infected with HCMV. In these cells TSP-1 expression was also significantly reduced by HCMV infection whereas expression of the p53 mutant variant remained unaltered. In both cell lines the decreased expression of TSP-1 mRNA occurred early after infection (4 hours), indicating that HCMV inhibits TSP-1 transcription during the immediate-early phase of infection before HCMV DNA replication. Inhibition of HCMV DNA synthesis by ganciclovir did not influence TSP-1 reduction whereas the antisense oligonucleotide ISIS 2922, complementary to HCMV immediate-early mRNA, completely prevented the HCMV-mediated TSP-1 suppression. These findings strongly suggest a novel role for HCMV in the modulation of angiogenesis due to p53-independent down-regulation of TSP-1 expression.

BACKGROUND There is evidence that the infection with human cytomegalovirus is clinically associated with enhanced metastasis and progression of neuroblastoma disease. An in vitro model with HCMV-infected neuroblastoma cells (NB) was used to investigate whether HCMV modulates the metastatic potential of NB. METHODS The neuroblastoma cell line UKF-NB-4 and its productively and persistently HCMV-infected variant UKF-NB-4AD169 were cocultured with human endothelial cells (EC). The rate of NB adherent to the endothelial monolayer and the rate of transmigrating NB was determined by means of combined reflexion interference contrast/phase contrast microscopy. RESULTS UKF-NB-4AD169 adhered to and transmigrated through cocultured EC monolayer to a significantly higher extent compared with the non-infected cell line UKF-NB-4. At the cell-to-cell contact sites between UKF-NB-4AD169 and EC the intercellular endothelial contacts loosened resulting in the formation of reversible focal openings in the monolayer. This phenomenon was not observed with UKF-NB-4. The transendothelial migration rate of UKF-NB-4AD169 was therefore significantly higher than that of UKF-NB-4. The formation of focal openings in the endothelial monolayer and the enhanced transmigration rate of UKF-NB-4AD169 was suppressed in the presence of phenantroline, suggesting that HCMV-induced proteinases might be responsible for this phenomenon. CONCLUSION The results confirm our assumption that HCMV has the ability to modulate functional properties of NB which are essential for the interactions with endothelial cells and thus for metastasation. The clinical relevance of these findings has to be further defined yet by means of prospective studies with HCMV-infected neuroblastoma patients. Proteinase inhibitors could be valuable in the therapeutic treatment of these patients.

In this retrospective investigation 7 patients operated on for recurrent trigeminal neuralgia via a suboccipital enlarged burr hole trepanation were evaluated. The intraoperative findings indicate that neo-compressive effects due to foreign material used during prior surgery are more important than adhesions around the nerve. Furthermore, the results of recurrent operations are encouraging as 6 of the 7 patients were painfree without additional neurological deficits.

Occult sacral meningoceles are a rare causative factor for neural claudication or radiculopathy. Facet joint cysts in the lumbar spine causing similar symptoms are much more frequent. We report the case of a patient with the radiological diagnosis of a facet joint cyst causing neural claudication. During surgery an occult sacral meningocele was diagnosed. In the literature there are only few cases reported. Hence, the findings and important differential diagnoses of cystic epidural lesions in the lumbar spine are discussed.

We observed the effects of antiviral therapy on CMV and/or oxidative-stress-induced stimulation of proinflammatory molecules including interleukin-8 (IL-8), melanoma growth stimulatory activity-α (GRO-α) and intercellular adhesion molecule 1 (ICAM-1) using human foreskin fibroblasts. Ganciclovir, foscarnet or cidofovir completely suppressed virus replication, as demonstrated by CMV late (L) antigen production. These drugs did not influence CMV immediate-early (IE) antigen expression and had no effects on CMV-induced cellular changes in IL-8, GRO-α and ICAM-1 levels. Phosphorothioate oligonucleotide (ISIS 2922) suppressed both CMV IE and L antigen by 99%. ISIS 2922 completely suppressed CMV-induced upregulation of both chemokines and ICAM-1. Induction of oxidative stress by H2O2 upregulated IL-8 expression. Oxidative stress and CMV infection showed synergistic effects on IL-8 expression. ISIS 2922 only partially inhibited the upregulation of IL-8 in infected cells treated with H2O2, whereas cotreatment with ISIS 2922 and antioxidants inhibited the upregulation almost completely. The results showed that inhibition of CMV IE expression alone or in combination with antioxidants is promising for the treatment of CMV disease.

SummaryNavigation in neuroendoscopy is becoming increasingly important, especially in complex interventions, such as tumour biopsies and cyst fenestrations. Theoretically, all existing image modalities are available to fulfill this need. Navigation with preoperative computed tomography (CT) or magnetic resonance images represents the ‘gold standard’ and is highly recommended for almost al neuroendoscopic operations. However, intra-operative changes of anatomy, due to, e.g. brain shift, cannot be taken into account by such navigation systems. For such cases, real-time imaging with sonography, CT or MRI may be helpful. At the moment, these methods are not routinely employed. Another interesting future development is digital image-processing in neuroendoscopy (as well as in other endoscopic procedures). With this new method, the control of dangerous intra-operative situations may become easier (because different modules are available) and documentation and training can be performed using the stored digital e...

A variety of cells such as leukocytes and tumor cells may adhere to endothelial cells and subsequently transmigrate into the solid tissue by involving specific intercellular molecular pathways. One important prerequisite for transendothelial migration is the loosening of endothelial cell-to-cell contact sites, which can be triggered by extravasating cells. Cytomegalovirus (CMV) has obviously evolved the ability not only to influence host cells floating in the blood stream to adhere to endothelial cells, but also to induce the formation of intercellular gaps within the endothelium, resulting in transendothelial migration. These features allow the virus to disseminate and evade the immune system. In coculture experiments with human endothelial monolayers and human CMV (HCMV)-infected neuroblastoma cells or leukocytes, changes in the integrity of the monolayer were observed and further analyzed on the molecular level. For example, HCMV may activate the integrin β1α5 (VLA-5) that triggers adhesion to endothelial cells with subsequent focal disruption of endothelial cell-to-cell connections. It is hypothesized that a Ca2+-independent pathway following VLA-5 binding disconnects the cadherin-catenin-actin complex within the endothelial cells. The loss of cadherin function causes the loss of contact to the neighboring endothelial cells and thus could represent an important mechanism in HCMV-induced cellular transendothelial migration and disruption of the endothelial integrity.

Despite the increased bandwidth and the Quality of Service (QoS) capabilities of ATM networks, measurements show that only a fraction of the available bandwidth can be used by applications with current approaches for realizing data communications over ATM employing the TCP/IP protocol suite [1, 2]. This is largely due to the unsuited protocol mechanisms and the lack of QoS support on transport level. Native Mode ATM offers full access to ATM's Quality of Service capabilities in homogenous ATM networks and provides support for a wide range of information streams with different properties and requirements [6]. In order to exploit the capabilities of ATM networks, and to optimally use the available resources, in the network and end system, new transport protocols are inevitable. In this paper we propose the transport protocols ADTS (ATM Data Transfer Service), which uses efficient protocol mechanisms suitable for ATM systems with a minimum of protocol processing overhead. We discuss implementation issues and present performance results obtained with a reference implementation of the ADTS protocol.

Cyclosporin A reduces the mitotic activity of allosensitized lymphocytes, but fails to limit emigration of these cells into the donor organ. However, the modulation of both lymphocyte proliferation and infiltration are desirable characteristics of immunosuppressive therapy. The calcium-channel blocker, verapamil, has recently been shown to effectively prevent the transmigration of CD4+ and CD8+ T cells through allogeneic endothelium. Mibefradil (Ro 40-5967) represents a new generation of calcium antagonists with high potency and long-term activity. To evaluate the immunosuppressive potential of this drug, the influence of mibefradil on lymphocyte adhesion to, horizontal locomotion along, and penetration through allogeneic endothelium (HUVEC) was performed. When lymphocytes were prestimulated for 24 hr with mibefradil, adhesion and penetration were dose-dependently reduced. The adhesion ID50 values were 3.4 microM (CD4+ T cells) versus 9.2 microM (CD8+ T cells) and 2.1 microM (CD4+ T cells) versus 3.9 microM (CD8+ T cells) with regard to penetration. Mibefradil also effectively blocked horizontal locomotion. Specific down-regulation of T-cell binding to the P-selection receptor (ID50: CD4+ T cells, 0.8 microM: CD8+ T cells, 1.2 microM) and to the intracellular adhesion molecule-1 (ICAM-1) receptor (ID50: CD4+ T cells, 1.9 microM; CD8+ T cells, 1.5 microM) by mibefradil seems to be responsible for the decreased adhesion and penetration rates. Reduction of intracellular F-actin in T lymphocytes could diminish cell locomotion. In conclusion, the potent suppressive properties of mibefradil support its use as a co-medication in cyclosporin A-based immunosuppressive therapy.

Primary cell cultures, such as isolated epithelial cells, neuronal cells, or hepatocytes are characterized by a very low mitotic activity. Monitoring of small changes in cell numbers requires staining with a DNA-specific dye with an extremely high sensitivity and a low inter- and intraassay variability. For this purpose, an ultrasensitive in vitro assay has been developed based on the fluorescent nucleic acid stain PicoGreen. PicoGreen has been shown to detect as little as 0.5 ng pure DNA or 10(2) cells (interassay SD < 10%, intraassay SD < 5%). This is far above the limit of sensitivity of conventional fluorochromes, such as Hoechst 33342 or propidium iodide. To obtain optimum efficacy of PicoGreen, cells were digested with papain for 20 h at 60 degrees C prior to staining. Under these conditions, the slope factor was calculated to be 0.105 relative fluorescence units (RFU)/cell, which is far superior to the slope factor of Hoechst 33342 (0.0137 RFU/cell) or propidium iodide (0.0077 RFU/cell). Analysis of the blank values revealed a very low autofluorescence of PicoGreen, which is only 1/50th of the autofluorescence of Hoechst 33342 and 1/5th of the autofluorescence of propidium iodide. Additional coating of the culture plates with extracellular matrix proteins to prevent cellular dedifferentiation did not influence the high sensitivity of PicoGreen. In conclusion, the PicoGreen-assay seems to be the method of choice when the growth capacity of primary cell cultures needs to be analyzed with high accuracy.

We studied the frequency of patients who had chronic subdural haematomas (CSDH) and Huntington's disease (HD) in a 1-year study period. In our department a total of 58 patients with CSDH were treated. Four patients (6.9% of them) had HD. Surgical evacuation of the haematoma was performed in all four cases with the use of a twist drill trepanation without a drainage system.

Light and oxygen are factors that are very much entangled in the reactive oxygen species (ROS) stress response network in plants, algae and cyanobacteria. The first obligatory step in understanding the ROS network is to separate these responses. In this study, a LC-MS/MS based quantitative proteomic approach was used to dissect the responses of Chlamydomonas reinhardtii to ROS, light and oxygen employing an interlinked experimental setup. Application of novel bioinformatics tools allow high quality retention time alignment to be performed on all LC-MS/MS runs increasing confidence in protein quantification, overall sequence coverage and coverage of all treatments measured. Finally advanced hierarchical clustering yielded 30 communities of co-regulated proteins permitting separation of ROS related effects from pure light effects (induction and repression). A community termed redox(II) was identified that shows additive effects of light and oxygen with light as the first obligatory step. Another community termed 4-down was identified that shows repression as an effect of light but only in the absence of oxygen indicating ROS regulation, for example, possibly via product feedback inhibition because no ROS damage is occurring. In summary the data demonstrate the importance of separating light, O₂ and ROS responses to define marker genes for ROS responses. As revealed in this study, an excellent candidate is DHAR with strong ROS dependent induction profiles.

Introduction: Paediatric neurovascular diseases include different patterns, such as cerebral aneurysms, arteriovenous or vein of Galen and cerebral cavernous malformations, as well as ischemic stroke and other infrequent clinical entities like Moyamoya disease. Management and treatment of this topic requires well-coordinated multidisciplinary care of pediatric neurosurgeons, interventional neuro-radiologists and paediatricians. Materials and methods: We present six cases of neurovascular pathologies in paediatric patients and highlight the multimodal treatment and management strategy. This case-series included patients with Vein of Galen malformation, Arteriovenous-malformation-bleeding, cerebellar ischaemic stroke, dissecting PICA-aneurysm and one patient with a vascular compression of the vestibular nerve inside the internal auditory meatus. Results: All patients show a good outcome because of a fast and interdisciplinary work and a close collaboration of the neurosurgeon, the neuroradiologist and the neuropadiatrician. Discussion: A multimodal therapy-management with an effective interdisciplinary setting including the pediatric neurosurgeon, the interventional neuroradiologist and the neuropaediatricians is necessary to reach the best outcome of the patient. Paediatric neurovascular diseases should be treated in an experienced centre with good infrastructure and good interdisciplinary work.

BACKGROUND: An important part of neurosurgical training is the improvement of surgical skills. Acquiring microsurgical skills follows a learning curve, influenced by specific exercises, feedback, and training. Aim of training should be rapid learning success. The study shows the way in which video-based training can influence the learning curve. METHODS: Over a period of 18 months (2011-2012) 12 residents were evaluated in spinal surgery (12 cases per resident) by a skilled evaluator based on different criteria. The evaluation criteria (exposition of important anatomy, intraoperative bleeding, efficacy of using bipolar cauterization) were weighted and added to a single quality-score. The participating residents were divided into two groups. Only one group (n = 5) received video-based training. RESULTS: Residents showed an individually different but explicit increase in microsurgical skills. The quality-score during the first surgery compared with the end point of the study demonstrated a faster improvement of surgical skills in the group with video-based training than in the group without special training. Considering all residents together, the video-training group displayed a steeper gradient of microsurgical success. Comparison of the single resident's microsurgical skills showed individual disparities. Various biases that influence the learning success are under examination. CONCLUSION: Video-based training can improve microsurgical skills, leading to an improved learning curve. An earlier entry of the learning curve plateau in the video-training group promotes a higher acquisition of surgical skills. Because of the positive effect, we plan to apply the video-based training model to other neurosurgical subspecialties, especially neurovascular and skull base surgery.

Object Neuroendoscopy is used more and more frequently in neurosurgical procedures and has become an important tool in the neurosurgical armamentarium. However, the main restriction of neuroendoscopy is the limited field of view. A better overview of the area of interest would increase surgical safety and decrease procedure-related morbidity rates. In the present study, the authors aimed to improve this restriction by using and comparing two algorithms to create endoscopic panoramic images, which increase the field of view during neuroendoscopic procedures. Methods Different endoscopic methods with or without a stand and with linear or circular endoscope movements were performed in cadaveric ventricles. Video of the endoscopy was used to create image mosaics of the lateral ventricle with the help of the Kourogi or LogSearch (LS) algorithm. In the LS algorithm, different template sizes were used. Three observers graded the quality of the image mosaic in terms of usefulness in surgery. The fastest frame rate was 3–4 frames/second. Results The LS algorithm with a larger template size showed significantly better results for the creation of image mosaics than the Kourogi algorithm in linear endoscopic movement with or without a stand. In circular endoscopic movements, the results seemed to be better with the LS algorithm but were not significantly different from those obtained with the Kourogi algorithm. In summary, image quality in the experimental paradigms was satisfying. Conclusions Results in the study showed that the creation of image mosaics is possible and reliable with the featured algorithms. Image mosaicking is an applicable device for neuroendoscopy and can increase the field of view during endoscopic procedures. Its use can increase the safety and the field of application of neuroendoscopy. However, faster frame rates will be required to create a smooth image for practical use during surgery.