Aim: To report the visual and angiographic outcomes after combination photodynamic therapy (PDT) and immunosuppression for inflammatory subfoveal choroidal neovascularisation (CNV). Methods: ...Retrospective review of six consecutive patients, five female and one male, aged 23–40 years with active subfoveal CNV secondary to posterior uveitis. Patients received either intravitreal triamcinolone or systemic immunosuppression (mycophenolate mofetil, tacrolimus) and PDT. Five patients had intravitreal triamcinolone injections and two patients were on systemic immunosuppression; all patients underwent PDT (mean two treatments). Visual acuity was measured on a 2 metre ETDRS chart and fluorescein angiograms were performed at each visit. Results: Median follow up was 15 months (range 10–31). Vision improved by a median of 13 letters in five patients and remained stable (±1 letter) in one patient. Median visual acuity improved from 20/160 at presentation to 20/40 at latest follow up (p = 0.03). There was a reduction in clinical exudation and cessation of angiographic leakage in all six patients. All interventions were well tolerated. Conclusion: Combination PDT and immunosuppression may be a useful therapeutic option for young patients with active inflammatory subfoveal CNV.
Effects of ketamine and lidocaine on electroencephalographic (EEG) changes were evaluated in minimally anaesthetized dogs, subjected to electric stimulus. Six dogs were subjected to six treatments in ...a crossover design with a washout period of one week. Dogs were subjected to intravenous boluses of lidocaine 2 mg/kg, ketamine 3 mg/kg, meloxicam 0.2 mg/kg, morphine 0.2 mg/kg and loading doses of lidocaine 2 mg/kg followed by continuous rate infusion (CRI) of 50 and 100 mcg/kg/min, and ketamine 3 mg/kg followed by CRI of 10 and 50 mcg/kg/min. Electroencephalogram was recorded during electrical stimulation prior to any drug treatment (before treatment) and during electrical stimulation following treatment with the drugs (after treatment) under anaesthesia. Anaesthesia was induced with propofol and maintained with halothane at a stable concentration between 0.85 and 0.95%. Pretreatment median frequency was evidently increased ( P < 0.05 ) for all treatment groups. Lidocaine, ketamine, and morphine depressed the median frequency resulting from the posttreatment stimulation. The depression of median frequency suggested evident antinociceptive effects of these treatments in dogs. It is therefore concluded that lidocaine and ketamine can be used in the analgesic protocol for the postoperative pain management in dogs.
Background: The Genomics of Drug Sensitivity in Cancer {GDSC; www.cancerRxgene.org) resource facilitates development of targeted cancer therapies through pre-clinical identification of therapeutic ...biomarkers. Materials and Methods: We are using pharmacogenomic profiling in a collection of 1,000 highly annotated cancer cell lines as a biomarker discovery platform by systematically linking pharmacological data with genomic information. The GDSC database can be used to guide the preclinical development of new therapies and to identify opportunities for re-purposing of existing molecules. Results: Established in 2012, the GDSC database has recently undergone a significant upgrade to increase functionality for mining data, and through the addition of new drug sensitivity datasets and analyses. The database now contains drug sensitivity data for over 210.000 experiments, describing response to 265 anti-cancer drugs across over 990 cancer cell lines. This includes drug sensitivity data for targeted agents and chemotherapeutics, incorporating clinically approved drugs, drugs in clinical development, and experimental compounds to diverse cancer-associated targets. To identify clinically relevant pharmacogenomic markers, we have derived a set of genomic alterations, including somatic mutations in cancer genes and recurrent copy number alterations, from the analysis of over 11,000 patient tumours. These alterations have been mapped onto our cell lines and integrated with drug sensitivity data using cancer-type specific and pan-cancer analyses. Conclusions: Analysis of GDSC data is through a web portal based on queries of specific anti-cancer drugs, cancer alterations, or cell lines of interest. Pharmacological and genomic dataset for our cell line collection can be accessed through the GDSC and COSMIC databases. GDSC provides a unique public resource incorporating large drug sensitivity and genomic datasets to facilitate discovery of new therapeutic biomarkers to accelerate the development of cancer therapies.
Epitaxial Ti3GeC2 thin films were deposited on 4° off-cut 4H-SiC(0001) using magnetron sputtering from high purity Ti, C, and Ge targets. Scanning electron microscopy and helium ion microscopy show ...that the Ti3GeC2 films grow by lateral step-flow with {112̄0} faceting on the SiC surface. Using elastic recoil detection analysis, atomic force microscopy, and X-Ray diffraction the films were found to be substoichiometric in Ge with the presence of small Ge particles at the surface of the film.
► Epitaxial growth of Ti3GeC2(0001) on 4H-SiC(0001) using magnetron sputtering. ► Ti3GeC2 films grow by lateral step-flow with {112̄0} faceting on the SiC surface. ► Films are substoichiometric in Ge with small Ge particles present at the surface.
Although the skeleton is extensively innervated by sensory nerves, the importance of this innervation to skeletal physiology is unclear. Neuronal connectivity between limbs is little studied and ...likely underestimated. In this study, we examined the effect of bone loading on spinal plasticity in young male Sprague–Dawley rats, using end-loading of the ulna and transynaptic tracing with the Bartha pseudorabies virus (PRV). PRV was inoculated onto the periosteum of the right ulna after 10 days of adaptation to a single period of cyclic loading of the right ulna (1,500 cycles of load at 4
Hz, initial peak strain of −3,750
μɛ). We found that neuronal circuits connect the sensory innervation of right thoracic limb to all other limbs, as PRV was detectable in the dorsal root ganglia (DRG) of left and right brachial and lumbosacral intumescences. We also found that mechanical loading of the right ulna induced plasticity in the spinal cord, with significant augmentation of the connectivity between limbs, as measured by PRV translocation. Within the spinal cord, PRV was predominantly found adjacent to the central canal and in the dorsal horns, suggesting that plasticity in cross-talk between limbs is likely a consequence of dendritic growth, and enhanced connectivity of propriospinal interneurons. In conclusion, the data clearly demonstrate that the innervation of the skeleton exhibits plasticity in response to loading events, suggesting the existence of a dynamic control system that may be of regulatory importance during functional skeletal adaptation.
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