Quasi-exact solutions for guided modes in two-dimensional materials with tilted Dirac cones.

We show that if the solutions to the (2+1)-dimensional massless Dirac equation for a given one-dimensional (1D) potential are known, then they can be used to obtain the eigenvalues and eigenfunctions for the same potential, orientated at an arbitrary angle, in a 2D Dirac material possessing tilted, anisotropic Dirac cones. This simple set of transformations enables all the exact and quasi-exact solutions associated with 1D quantum wells in graphene to be applied to the confinement problem in tilted Dirac materials such as 8-Pmmn borophene. We also show that smooth electron waveguides in tilted Dirac materials can be used to manipulate the degree of valley polarization of quasiparticles travelling along a particular direction of the channel. We examine the particular case of the hyperbolic secant potential to model realistic top-gated structures for valleytronic applications.

Mechanisms regulating spill-over of synaptic glutamate to extrasynaptic NMDA receptors in mouse substantia nigra dopaminergic neurons.

N-Methyl-D-aspartate glutamate receptors (NMDARs) contribute to neural development, plasticity and survival, but they are also linked with neurodegeneration. NMDARs at synapses are activated by coincident glutamate release and depolarization. NMDARs distal to synapses can sometimes be recruited by 'spill-over' of glutamate during high-frequency synaptic stimulation or when glutamate uptake is compromised, and this influences the shape of NMDAR-mediated postsynaptic responses. In substantia nigra dopamine neurons, activation of NMDARs beyond the synapse during different frequencies of presynaptic stimulation has not been explored, even though excitatory afferents from the subthalamic nucleus show a range of firing frequencies, and these frequencies change in human and experimental Parkinson's disease. This study reports that high-frequency stimulation (80 Hz/200 ms) evoked NMDAR-excitatory postsynaptic currents (EPSCs) that were larger and longer lasting than those evoked by single stimuli at low frequency (0.1 Hz). MK-801, which irreversibly blocked NMDAR-EPSCs activated during 0.1-Hz stimulation, left a proportion of NMDAR-EPSCs that could be activated by 80-Hz stimulation and that may represent activity of NMDARs distal to synapses. TBOA, which blocks glutamate transporters, significantly increased NMDAR-EPSCs in response to 80-Hz stimulation, particularly when metabotropic glutamate receptors (mGluRs) were also blocked, indicating that recruitment of NMDARs distal to synapses is regulated by glutamate transporters and mGluRs. These regulatory mechanisms may be essential in the substantia nigra for restricting glutamate diffusion from synaptic sites and keeping NMDAR-EPSCs in dopamine neurons relatively small and fast. Failure of glutamate transporters may contribute to the declining health of dopamine neurons during pathological conditions.

Memantine block depends on agonist presentation at the NMDA receptor in substantia nigra pars compacta dopamine neurones.

NMDA glutamate receptors (NMDARs) have critical functional roles in the nervous system but NMDAR over-activity can contribute to neuronal damage. The open channel NMDAR blocker, memantine is used to treat certain neurodegenerative diseases, including Parkinson's disease (PD) and is well tolerated clinically. We have investigated memantine block of NMDARs in substantia nigra pars compacta (SNc) dopamine neurones, which show severe pathology in PD. Memantine (10 µM) caused robust inhibition of whole-cell (synaptic and extrasynaptic) NMDARs activated by NMDA at a high concentration or a long duration, low concentration. Less memantine block of NMDAR-EPSCs was seen in response to low frequency synaptic stimulation, while responses to high frequency synaptic stimulation were robustly inhibited by memantine; thus memantine inhibition of NMDAR-EPSCs showed frequency-dependence. By contrast, MK-801 (10 µM) inhibition of NMDAR-EPSCs was not significantly different at low versus high frequencies of synaptic stimulation. Using immunohistochemistry, confocal imaging and stereological analysis, NMDA was found to reduce the density of cells expressing tyrosine hydroxylase, a marker of viable dopamine neurones; memantine prevented the NMDA-evoked decrease. In conclusion, memantine blocked NMDAR populations in different subcellular locations in SNc dopamine neurones but the degree of block depended on the intensity of agonist presentation at the NMDAR. This profile may contribute to the beneficial effects of memantine in PD, as glutamatergic activity is reported to increase, and memantine could preferentially reduce over-activity while leaving some physiological signalling intact.

Tissue biomarkers for prostate cancer radiation therapy.

Prostate cancer is the most common cancer and second leading cause of cancer deaths among men in the United States. Most men have localized disease diagnosed following an elevated serum prostate specific antigen test for cancer screening purposes. Standard treatment options consist of surgery or definitive radiation therapy directed by clinical factors that are organized into risk stratification groups. Current clinical risk stratification systems are still insufficient to differentiate lethal from indolent disease. Similarly, a subset of men in poor risk groups need to be identified for more aggressive treatment and enrollment into clinical trials. Furthermore, these clinical tools are very limited in revealing information about the biologic pathways driving these different disease phenotypes and do not offer insights for novel treatments which are needed in men with poor-risk disease. We believe molecular biomarkers may serve to bridge these inadequacies of traditional clinical factors opening the door for personalized treatment approaches that would allow tailoring of treatment options to maximize therapeutic outcome. We review the current state of prognostic and predictive tissue-based molecular biomarkers which can be used to direct localized prostate cancer treatment decisions, specifically those implicated with definitive and salvage radiation therapy.

Piloting education days for patients with early rheumatoid arthritis and their partners: a multidisciplinary approach.

OBJECTIVES: To develop, pilot, refine and reassess an education day presented by a rheumatology multidisciplinary team (MDT) for recently diagnosed (less than six months) rheumatoid arthritis (RA) patients and their partners/carers. METHODS: A patient education day was developed drawing on an assessment of local patient educational needs and preferences and input from a rheumatology MDT. Feedback from the first education day (2004) (Day 1; 12 patients; age range 19-63 years (median 46); 10 of whom were accompanied by a partner) informed the development of a second education day (2005) (Day 2; 19 patients; age range 36-75 years (median 57.5); 13 of whom were accompanied by a partner). Participants completed evaluation forms on both days and at follow-up between six and seven weeks later, rating each session on a 5-point scale on dimensions of 'informative', 'useful', 'interesting' and 'enjoyable'. A global rating of the day's 'usefulness' was completed at the end of each day on a 10-point scale. Participants were asked to write comments on each session and on aspects of the entire day. RA knowledge, and general and RA-specific self-efficacy were also measured on day 2 (and at follow-up) using the 12-item Patient Knowledge Questionnaire, the 10-item generalized self-efficacy scale and a four-item RA-specific self-efficacy scale. Both qualitative and quantitative methodologies were used in the analysis. RESULTS: Ratings for individual sessions were all high, with no session being rated below 4 out of 5 (1 = 'totally disagree' to 5 = 'totally agree') on both days. The majority of patients (84%) and their partners (57%) responded to the follow-up. Many had used the information package distributed on the day. Some patients and their partners reported positive changes in RA management. Although patient knowledge did not increase significantly (medians 11 at both time points, p = 0.054) (Day 2), RA self-efficacy improved (baseline 11 and 14, respectively), suggesting that patients were more confident in managing their condition (p = 0.010). CONCLUSIONS: The development of this 'local' education and information intervention was carried out in line with Medical Research Council guidelines, and the lessons learned from Day 1 informed further development for Day 2. A one-day format for education of early RA involving the rheumatology MDT was rated highly by participants and warrants further examination. Although this study was a small 'local' intervention, its strengths are that it informs the possibility of wider developments of this kind using a MDT.

[Additional treatment in chronic pain syndrome due to hip and knee arthritis with the selective serotonin reuptake inhibitor fluvoxamine (Fevarin]. / Eine additive Therapie chronischer Schmerzen bei fortgeschrittener Gon-/Coxarthrose mit dem selektiven Serotonin-Reuptake-Hemmer Fluvoxamin (Fevarin).

OBJECTIVE: The aim of this study was to investigate the effectiveness and safety of the selective serotonin reuptake inhibitor fluvoxamine (Flevarin) in patients with a chronic pain syndrome due to hip and knee arthritis. METHODS: We prospectively investigated 60 patients in a single-centre double-blind study. The group was divided into two groups (M1 fluvoxamine; M2 placebo) each containing 30 patients, age ranging from 30 to 80 years. During treatment results were evaluated using several scales once at the beginning (V1) followed by weekly evaluations (V1-V8) and one final investigation at the end of treatment (V9). The investigated medication consisted of 50-150 mg fluvoxamine. In addition other drugs such as NSAID were administered (diclofenac, piroxicam, ibuprofen). RESULTS: Both groups (M1 and M2) showed a reduction of pain during treatment using the visual analogue scale (VAS). However, no statistical difference was found between both groups concerning pain reduction at any time. A significant pain relief was monitored in the patients of the M1 group towards the end of treatment. Concerning the daily impairment because of pain measured by the Griss scale an improvement was seen in 70 % of the patients receiving fluvoxamine versus 44 % in patients receiving placebo. Additionally, an improvement in the M1 group was seen in the WOMAC scale and in factors such as pain, stiffness and mobility compared to the M2 group. Using the CGI scale, 56.6 % of the M1 group compared to 37.9 % of the M2 group were stating that their overall status had improved "much" or "very much" at the end of the treatment (V9). A depression had been excluded in all patients. No statistical differences were seen in the Bf scale (von Zerssen) during all evaluations (V1 to V9). During the whole study 127 side effects were registered in 49 patients. None of the 5 severe events were related to the investigated drug. CONCLUSION: Considering the good effects in combination with very few side effects, a positive cost-effectiveness relation for the usage of fluvoxamine can be stated in patients with chronic pain syndrome due to hip and knee arthritis.

[Gorham-stout disease]. / Morbus Gorham-Stout.

INTRODUCTION: Gorham-Stout disease is a rare entity characterised by a massive osteolysis and typically starts monocentrically in an isolated bone. Concerning the pathogenesis, haemangiomatosis and an overstimulation of osteoclasts are discussed which cause a progressive destruction of the affected skeleton and involve neighbouring soft tissue in the further progress of the disease. CASE REPORT: This report is about a 45-year-old male who suffered a traumatic insult. X-rays showed an osteolytic lesion in the 4th lumbar vertebra with depression in the ventral roof plate. Further radiological investigation has ruled out a malignant lesion and suggested Gorham-Stout disease as a diagnosis. Therapy has been carried out using bisphosphonates as well as fractioned radiation of the vertebra with 30 Gy under which a remission was achieved. DISCUSSION: The progress of our case correlates with published data in the literature. Spinal lesions are rare, but possible neurological complications or a possible chylothorax reflect the high mortality rate. We found no complications in our case. CONCLUSION: Despite massive osteolysis with resorption of up to a whole bone segment, radiation with a dose of 22.8 Gy and the use of antiresorptive substances, as reported in our case, have often been shown to limit the destructive progression of the disease. A causal therapy of the disease is not known yet.

[Therapeutic efficiency in multisegmental fusions of the lumbar spine]. / Therapeutische Effizienz langstreckiger Fusionen im Bereich der LWS.

AIM: The aim of this study was to evaluate of the efficiency of an internal fixateur used since 1998 in multisegmental spondylodesis of the lumbar spine. METHOD: The prospective study included 105 patients with degenerative changes or instabilities of the lumbar spine, who underwent an anterior and posterior stabilisation of more than two segments. The minimum period of follow-up was more than 6 months. There were several objective scores used for the evaluation of the efficiency (Oswestry score/visual analogue scale [VAS]). In addition, the quality of the new internal implant was assessed concerning the rate of loosening and failure of the implant. This new internal fixateur, produced as a titanium alloy, consists of pedicle screws and longitudinal rods with 5 mm diameter and connection elements. Upon pulling the nut a square stabilised situation is created. Altogether the three-segmental stabilisations predominated (n=77), 23 patients received a four-segmental, four patients a five-segmental stabilisation and one received a stabilisation of six levels, mainly involving the segments L3/4 to L5/S1. Because of severe deformities in 14 cases the pedicle screws were applied by computer-assisted navigation (Navitrak). RESULTS: In 12 patients (11.4%) radiological signs of loosening of the inserted pedicle screws in the vertebra were diagnosed. The radiological analysis resulted in pseudarthrosis of 4 (1.2%) of the 349 amalgamated segments. There were no cases of material failure. The average value of the pain score preoperatively (VAS) was 7.7 (5-10, SA 1.3) and postoperatively 4.6 (1-10, SA 1.8). With regard to the Oswestry disability index the preoperative average value amounted to 51.9% (30-91, SA 11.8) and postoperatively 35% (12-74, SA 11.8). In all 98 (93.3%) patients were satisfied, 7 (6.7%) patients reported a decline of the subjective outcome. CONCLUSION: This system achieved a high degree of patient satisfaction and showed a low rate of pseudarthrosis. Furthermore, it can be inserted for short and long fusions, as well in deformities.

[Mid-term therapeutic effect analysis of cementless total knee arthroplasty without patella replacement].

OBJECTIVE: To explore the flexibility and reliability of cementless total knee arthroplasty (TKA) without patella replacement through a retrospective study of the mid-term therapeutic effect of the treatment of the patients. METHODS: From June 1997 to March 2000, a consecutive series of 152 (152 knees) cementless TKA performed in Hessing-Stiftung was studied. Among them, there were 63 males and 89 females, with 70 left knees and 82 right knees. Their ages ranged from 51 years to 72 years, with an average of 59 years. There were 146 cases of osteoarthritis and 6 cases of traumatic arthritis. The course of the disease lasted for 1.0 years to 3.5 years. The EFK prostheses of German Plus company were used in all the cases. The HSS score before the operation was 41.5 +/- 12.3, and the average range of motion was 55 degrees (ranging from 30 degrees to 90 degrees). RESULTS: Five patients underwent anterior knee pain, and the pain was released after the appropriate treatment. No deep infection happened in all cases. A total of 145 patients (145 knees) were followed up for 5 years to 8 years. The HSS score was 87.5 +/- 8.2 at the end of the follow-up, showing significant difference (P < 0.05). The average range of motion was 95 degrees (ranging from 90 degrees to 110 degrees). Partial radiolucencies occurred at the tibia side in 18 knees 3 to 6 months after the operation. Among them, the width was less than 2 mm in 15 knees without symptom, and more than 2 mm in 3 knees. There were 2 of the 3 knees which were revised at the tibia side because of the aseptic loosing, while 1 patient had only mild pain in the knee during the follow-up, with no sign of loosing. CONCLUSION: The mid-term effect of cementless TKA is satisfactory. The ingrowth of femur and tibial bones is reliable. The early stage migration of the component is the main reason of loosing. Satisfying outcomes can also be achieved without patella replacement during TKA.

Clinical outcome after transfixation of the epiphysis with Kirschner wires in unstable slipped capital femoral epiphysis.

Treatment of slipped capital femoral epiphysis (SCFE) is still controversial. Agreement has not yet been reached on the appropriate time to perform surgery, the necessity of repositioning manoeuvres, the type of implants for stabilisation, or the need for prophylactic treatment of the contralateral side. In this retrospective study, we present 29 patients with unstable (acute and acute-on-chronic) SCFE treated by internal fixation of the epiphysis with three or four Kirschner wires both therapeutically on the affected side and prophylactically on the not (yet) affected side. After hardware removal and mean follow-up of 3.5 years, radiological and clinical examination of hip function was carried out. X-ray in two planes showed no incidence of any slip progression. Applying the score used by Heyman and Herndon, 18 results (62.1%) were classified as excellent, nine (31.1%) as good, one (3.4%) as fair, and one (3.4%) as poor. The rate of severe complications such as chondrolysis and avascular necrosis of the femoral head was low in our series (0% and 6.8%, respectively). This form of therapeutic management shows good clinical results with low complication rates. The slip can be efficiently stabilised, progression is reliably prevented, and remodelling of the joint gives the patient good overall hip function. We see no indication for emergency surgery.

[Retransfusion of unwashed drainage blood after total hip and knee arthroplasty]. / Retransfusion ungewaschenen Drainageblutes nach Hüft- und Knieendoprothesenimplantationen.

The method of retransfusion of drainage blood as known from the literature was investigated in a prospectiv study regarding effectivness and rate of side effects. 200 patients who underwent total hip and knee arthroplasty were investigated concerning hemoglobin, hematocrit, amount and quality of the retransfused drainage blood, the amount of autologous and homologous transfusions as well as complications and costs. 100 of these patients were selected as the control group. The amount of the retransfused drainage blood after hip arthroplasty amounted an average of 387 +/- 194 ml and after knee arthroplasty 595 +/- 250 ml. The retransfused blood had an average hemoglobin of 5,2 +/- 0,9mmol/l with a hematocrit of 0,24 0,05. No complications directly associated to the retransfusion were found. The need of transfusion was reduced for patients with knee arthroplasty about 30% and for hip arthroplasty about 25%. The retransfusion of unwashed drainage blood is a sufficient method to reduce perioperative homologous blood transfusion in patients with arthroplasty of hip and knee. Substantial complications were not observed, so that this method seems to be save enough for clinical usage. The method is easy to handle and usable without special technical devices. The autologous retransfusion of drainage blood can contribute to lower costs in patients treatement.

[Preoperative halo-traction in severe paralytic scoliosis]. / Die präoperative Halo-Extension bei hochgradiger Lähmungsskoliose.

AIM: During the past decades the treatment of severe paralytic scoliosis has developed towards surgical treatment. However there is controversial discussion about the need of pre-operative Halo-traction. The aim of this study was to built two groups of patients -- one group with and another one without pre-operative Halo-traction -- and to compare the results after surgical correction of scoliotic deformity with data from literature. METHOD: Between 2000-2003 twenty-five patients with severe neuromuscular spine deformity were treated surgically. Eight patients had preoperative Halo-traction, seventeen patients underwent directly operative correction and instrumentation. The evaluation included the pre- and postoperative X-rays as well those after Halo-traction before surgery. RESULTS: In the group without Halo-traction the scoliotic angle according to Cobb was reduced from 77 degrees to 33 degrees on average (mean correction of 44 degrees [57 %]). In the group with Halo-traction scoliosis was reduced from 85 degrees to 33 degrees on average (mean correction of 52 degrees [61 %]). CONCLUSION: The preoperative Halo-traction in patients with severe neuromuscular scoliosis indeed leads to radiologically higher correction, but this is not significant (p = 0.19) and only in single cases clinically relevant. In our point of view except from specific indications Halo-traction should not be applied in general as a standard procedure.

[Prospective screw misplacement analysis after conventional and navigated pedicle screw implantation]. / Prospektive Schraubenfehllagenanalyse nach konventioneller und navigierter Pedikelschraubenimplantation.

BACKGROUND: [corrected] The aim of this prospective study was (1) to evaluate the accuracy of pedicle screw placement using Computer - Assisted Orthopedic - Surgery (CAOS) in comparison to conventionelly image intensifier controlled pedicle screw instrumentation, (2) to compare our results with data from literature and (3) report our experiences with this technique. PATIENTS AND METHODS: Between 11/00 and 11/01 sixteen patients planned for spine surgery were subsequently recruited. Pedicle screw instrumentation was done in each patient as well with computer aided surgery (CAOS, SurgiGate-System, Medivision, Stratec Medical, Swiss) as also with image intensifier control, allowing for intraindividual comparison. Evaluation of pedicle screw placement was carried out with postoperative computed tomography (CT) or magnetic resonance imaging (MRI). RESULTS: 33 of altogether 36 pedicle screws inserted with Computer-Assistance (CAOS) were correctly placed (91,7%), however only 17 of altogether 24 pedicle screws inserted under image intensifier control (70,8%). The difference of frequency of screw misplacement between Computer-aided and image intensifier controlled instrumentation was statistically significant (p<0.05; chi-square test). CONCLUSION: Computer assisted surgery reduces significantly the misplacement rate of pedicle screws and remains for experienced spine surgeons an important support in the operative treatment of complex spinal deformities in future. Additionally it can be expected that Computer-Navigation will also spread out in the field of minimal-invasive spinal surgery, e.g. the kyphoplasty. The use of this technique supports beside the medical-technical knowledge an improved three-dimensional orientation in the education of spine surgeons.

[Surgical therapy for spondylolysis and spondylolisthesis]. / Operative Therapie bei Spondylolyse und Spondylolisthese.

The therapy for spondylolysis and spondylolisthesis is challenging in view of the large variety of treatment options. A general, standardized therapeutic concept has still not been established. Adequate therapy depends on different parameters and personal experience. Beside direct repair surgery of spondylolysis and low grade spondylolisthesis, dorsal, ventral and combined dorsoventral surgery, with or without instrumentation, are indicated depending on patients age and severity of the slip. Complications such as pseudarthrosis and progression of the slip develop in a given percentage of cases, but these are not significantly correlated with clinical symptoms. Decompression is necessary in high grade slippage with neurologic impairment, especially paresis. Reposition is associated with a higher risk of neurologic complications. Fusion in situ without instrumentation, even in moderate and severe spondylolisthesis, shows good clinical results with high fusion rates and without the increased risk of progression and pseudarthrosis. In many cases, it is an effective, safe and economic therapeutic option.

[Bone harvesting from the iliac crest]. / Knochenspanentnahme am Becken. Techniken und Probleme.

BACKGROUND: Autogenous bone grafts from the iliac crest are frequently harvested for autologous bone transplantation. Although an autologous bone transplant does improve the local bone healing potency, significant donor site morbidity must be considered. METHODS: In this study we elucidate special bone harvesting techniques from the iliac crest and review the literature related to clinical significance of donor site morbidity. Furthermore, our own experiences are compared and discussed critically with relevant data of other investigators. RESULTS: The increasing number of scientific publications which focus on bone harvesting techniques and related complications in recent years indicate the high interest and relevance of this issue. There is a tendency to alternatives such as biomaterials as bone substitutes, whereas the role of growth factors and cell therapeutics in the treatment of bony defects are still being evaluated in clinical studies. CONCLUSION: Although autologous, heterotopic bone transplantation is still the gold standard in the treatment of bony defects, there is a tendency towards the application of biomaterials, stem cells, and growth factors. Conscientious observation of relevant anatomic considerations during bone harvesting procedures may help to avoid complications.

[Correction of forearm deformities in children with multiple cartilaginous osteochondromas]. / Deformitätenkorrektur am Unterarm bei Kindern mit multipler kartilaginärer Exostosenkrankheit.

AIM: Deformity of the forearm with shortening and bowing is common in children with multiple cartilaginous osteochondromas. The objective of this study was to evaluate the benefit of ulnar lengthening using an external fixateur in these patients. METHOD: 9 patients (10 cases) underwent surgery of the forearm between 1995 and 2001 and were evaluated using a standard protocol. The mean follow-up was 33.6 months, the mean age at operation 8.9 years. All patients were treated with ulnar lengthening, in 6 cases combined with an excision of the osteochondromas. RESULTS: Four out of ten patients did show an improvement in postoperative forearm rotation, two deteriorated and 4 presented unchanged. Wrist motion improved in 7 patients and remained unchanged in 3. The postoperative radial articular angle showed an improvement in 6, the carpal slip in 9 of the patients. The preoperative radial head dislocation in one patient remained unchanged postoperatively. CONCLUSION: The authors advocate this therapeutic concept for the correction of forearm deformity in multiple hereditary osteochondromas to prevent a progression of the deformity and to establish carpal stability. A significant improvement of forearm and wrist function could not be reached.