Lack of axon regeneration in the adult CNS has been attributed partly to myelin inhibitors and the properties of astrocytes. After spinal cord injury, proliferating astrocytes not only represent a physical barrier to regenerating axons but also express and secrete molecules that inhibit nerve growth, including chondroitin sulfate proteoglycans (CSPGs). Epidermal growth factor receptor (EGFR) activation triggers astrocytes into becoming reactive astrocytes, and EGFR ligands stimulate the secretion of CSPGs as well as the formation of cribriform astrocyte arrangements that contribute to the formation of glial scars. Recently, it was shown that EGFR inhibitors promote nerve regeneration in vitro and in vivo. Blocking a novel Nogo receptor interacting mechanism and/or effects of EGFR inhibition on astrocytes may underlie these effects. Here we show that rats subjected to weight-drop spinal cord injury can be effectively treated by direct delivery of a potent EGFR inhibitor to the injured area, leading to significantly better functional and structural outcome. Motor and sensory functions are improved and bladder function is restored. The robust effects and the fact that other EGFR inhibitors are in clinical use in cancer treatments make these drugs particularly attractive candidates for clinical trials in spinal cord injury.

Inhibition of RhoA has been shown to enhance axonal regeneration following spinal cord injury. Here we mapped mRNA expression patterns of RhoA, B, and C, Rac1, Cdc42, and Tc10 in spinal cord, sensory ganglia, and sensorimotor cortex in uninjured rats, and following spinal cord injury or sham laminectomy. In the intact spinal cord, neurons displayed high levels of Rac1, Cdc42, and Tc10 mRNA hybridization signal. GFAP-immunoreactive astrocytes expressed primarily RhoB and Rac1, while oligodendrocyte-like cells expressed RhoA, Rac1, and Cdc42. Injury caused profound, long-lasting upregulation of RhoA, Rac1, Cdc42, and Tc10 mRNA in the spinal cord, while RhoB was modestly increased and RhoC did not change. GFAP-immunoreactive reactive astrocytes exhibited a dramatic increase of RhoA mRNA expression along with increases of Rac1 and Cdc42. Injury also led to elevation of RhoA, Cdc42, and Tc10 in neurons and modest increases of RhoA, Rac1, and Tc10 in oligodendrocyte-like cells. Laminectomy caused similar, but less pronounced alterations of investigated mRNA species. In dorsal root ganglia neuronal RhoA, Rac1, Cdc42, and Tc10 mRNA levels were increased similarly by spinal cord injury and sham surgery. The CST pyramidal cells expressed Tc10 mRNA and the CST itself was Tc10-immunoreactive. Tc10-immunoreactivity disappeared distal to injury. We conclude that there are gene-specific patterns of expression of the six different Rho-GTPases in normal spinal cord and dorsal root ganglia, and that specific changes of temporal and spatial expression patterns occur in response to spinal cord injury, suggesting different roles of these GTPases in the cellular sequelae of CNS injury.

Background Neer Group VI proximal humeral fractures often are related to persistent disability despite surgical treatment. We retrospectively compared the outcome after open reduction and internal fixation with the PHILOS

Background Reconstruction of the extensor mechanism after resection of the proximal tibia is challenging, and several methods are available. A medial gastrocnemius flap commonly is used, although it may be associated with an extensor lag. This problem also is encountered, although perhaps to a lesser extent, with other techniques for reconstruction of the extensor apparatus. It is not known how such lag develops with time and how it correlates with functional outcome. Questions/purposes We therefore (1) assessed patellar height with time, (2) correlated patellar height with function using the Musculoskeletal Tumor Society (MSTS) score, and (3) correlated patellar height with range of motion (ROM) after medial gastrocnemius flap reconstruction. Methods Sixteen patients underwent tumor endoprosthesis implantation and extensor apparatus reconstruction between 1997 and 2009 using a medial gastrocnemius flap after sarcoma resection of the proximal tibia. These patients represented 100% of the population for whom we performed extensor mechanism reconstructions during that time. The minimum followup was 2 years (mean, 5 years; range, 2-11 years). Fourteen patients were alive at the time of this study. We used the Blackburne-Peel Index to follow patellar height radiographically with time. Functional outcomes were assessed retrospectively using the MSTS, and ROM was evaluated through active extensor lag and flexion. Results Eleven patients had patella alta develop, whereby the maximal patellar height was reached after a mean of 2 years and then stabilized. More normal patellar height was associated with better functional scores, a smaller extensor lag, but less flexion; the mean extensor lag (and flexion) of patients with patella alta was 17°(and 94°) compared with only 4°(and 77°) without. Conclusions In our patients patella alta evolved during the first 2 postoperative years. Patella alta is associated with extensor lag, greater flexion, and worse MSTS scores.

A variety of tests of sensorimotor function are used to characterize outcome after experimental spinal cord injury (SCI). These tests typically do not provide information about chemical and metabolic processes in the injured CNS. Here, we used 1H-magnetic resonance spectroscopy (MRS) to monitor long-term and short-term chemical changes in the CNS in vivo following SCI. The investigated areas were cortex, thalamus/striatum and the spinal cord distal to injury. In cortex, glutamate (Glu) decreased 1 day after SCI and slowly returned towards normal levels. The combined glutamine (Gln) and Glu signal was similarly decreased in cortex, but increased in the distal spinal cord, suggesting opposite changes of the Glu/Gln metabolites in cortex and distal spinal cord. In lumbar spinal cord, a marked increase of myo-inositol was found 3 days, 14 days and 4 months after SCI. Changes in metabolite concentrations in the spinal cord were also found for choline and N-acetylaspartate. No significant changes in metabolite concentrations were found in thalamus/striatum. Multivariate data analysis allowed separation between rats with SCI and controls for spectra acquired in cortex and spinal cord, but not in thalamus/striatum. Our findings suggest MRS could become a helpful tool to monitor spatial and temporal alterations of metabolic conditions in vivo in the brain and spinal cord after SCI. We provide evidence for dynamic temporal changes at both ends of the neuraxis, cortex cerebri and distal spinal cord, while deep brain areas appear less affected.

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Objective To evaluate doctors' coffee consumption at work and differences between specialties.Design Single centre retrospective cohort study. Setting Large teaching hospital in Switzerland.Participants 766 qualified doctors (425 men, 341 women) from all medical specialties (201 internal medicine, 76 general surgery, 67 anaesthetics, 54 radiology, 48 orthopaedics, 43 gynaecology, 36 neurology, 23 neurosurgery, 96 other specialties).Data source Staff purchasing history from staff canteens' electronic payment system linked to separate anonymised personal data from the human resource database. Main outcome measure Numbers of coffees purchased per person per year.Results 84% (644) of doctors purchased coffee at one of the hospital canteens. 70 772 coffees were consumed by doctors in 2014. There was a significant association between specialty and yearly coffee purchasing (F=12.45; P<0.01). On average orthopaedic surgeons purchased the most coffee per person per year (mean 189, SD 136) followed by radiologists (177, SD 191) Conclusions Doctors commonly use coffee as a stimulant. Substantial variation exists between specialties. Surgeons drink notably more coffee than physicians, with orthopaedic surgeons consuming the greatest amount in the communal cafeteria setting, though this might reflect social tendencies rather than caffeine dependency. Hierarchical position is positively correlated with coffee consumption and generosity with regard to buying rounds of coffee.

Alcohol sclerosing therapy administered in the clinic setting without alcohol is not an effective treatment in the nonoperative management of painful interdigital neuromas and has been abandoned in our clinic.