Light-Induced Fos Expression in Intrinsically Photosensitive Retinal Ganglion Cells in Melanopsin Knockout (Opn4−/−) Mice

Retinal ganglion cells that express the photopigment melanopsin are intrinsically photosensitive (ipRGCs) and exhibit robust synaptically driven ON-responses to light, yet they will continue to depolarize in response to light when all synaptic input from rod and cone photoreceptors is removed. The light-evoked increase in firing of classical ganglion cells is determined by synaptic input from ON-bipolar cells in the proximal sublamina of the inner plexiform layer. OFF-bipolar cells synapse with ganglion cell dendrites in the distal sublamina of the inner plexiform layer. Of the several types of ipRGC that have been described, M1 ipRGCs send dendrites exclusively into the OFF region of the inner plexiform layer where they stratify near the border of the inner nuclear layer. We tested whether M1 ipRGCs with dendrites restricted to the OFF sublamina of the inner plexiform layer receive synaptic ON-bipolar input by examining light-induced gene expression in vivo using melanopsin knockout mice. Mice in which both copies of the melanopsin gene (opn4) have been replaced with the tau-lacZ gene (homozygous tau-lacZ+/+ knockin mice) are melanopsin knockouts (opn4−/−) but M1 ipRGCs are specifically identified by their expression of β-galactosidase. Approximately 60% of M1 ipRGCs in Opn4−/− mice exposed to 3 hrs of light expressed c-Fos; no β-galactosidase-positive RGCs expressed c-Fos in the dark. Intraocular application of L-AP4, a compound which blocks transmission of visual signals between photoreceptors and ON-bipolar cells significantly reduced light-evoked c-Fos expression in M1 ipRGCs compared to saline injected eyes (66% saline vs 27% L-AP4). The results are the first description of a light-evoked response in an ipRGC lacking melanopsin and provide in vivo confirmation of previous in vitro observations illustrating an unusual circuit in the retina in which ganglion cells sending dendrites to the OFF sublamina of the inner plexiform layer receive excitatory synaptic input from ON-bipolar cells

Reviewing the integration of patient data: how systems are evolving in practice to meet patient needs

<p>Abstract</p> <p>Background</p> <p>The integration of Information Systems (IS) is essential to support shared care and to provide consistent care to individuals – patient-centred care. This paper identifies, appraises and summarises studies examining different approaches to integrate patient data from heterogeneous IS.</p> <p>Methods</p> <p>The literature was systematically reviewed between 1995–2005 to identify articles mentioning patient records, computers and data integration or sharing.</p> <p>Results</p> <p>Of 3124 articles, 84 were included describing 56 distinct projects. Most of the projects were on a regional scale. Integration was most commonly accomplished by messaging with pre-defined templates and middleware solutions. HL7 was the most widely used messaging standard. Direct database access and web services were the most common communication methods. The user interface for most systems was a Web browser. Regarding the type of medical data shared, 77% of projects integrated diagnosis and problems, 67% medical images and 65% lab results. More recently significantly more IS are extending to primary care and integrating referral letters.</p> <p>Conclusion</p> <p>It is clear that Information Systems are evolving to meet people's needs by implementing regional networks, allowing patient access and integration of ever more items of patient data. Many distinct technological solutions coexist to integrate patient data, using differing standards and data architectures which may difficult further interoperability.</p

Single-dose pharmacokinetics and cardiovascular effects of oral pimobendan in healthy cats

Abstract not availableM. Yata, A.J. McLachlan, D.J.R. Foster, A.S. Hanzlicek, N.J. Beijerin

Abiotrofia della corteccia cerebellare in tre American Pit Bull Terriers

none8- ISSN:noneDe Martino L; BERNARDINI M.; Cizinauskas; Hanzlicek D; Botteron C; Srenk P; Gailleard C; Jaggy A.De Martino, L; Bernardini, Marco; Cizinauskas, ; Hanzlicek, D; Botteron, C; Srenk, P; Gailleard, C; Jaggy, A

Reduced susceptibility to fluconazole in a cat with histoplasmosis

Case summary An 11-year-old neutered male domestic longhair cat was diagnosed with histoplasmosis from fine-needle aspirates of an abdominal lymph node. Lymph node size initially decreased with fluconazole therapy (11.8 mg/kg PO q12h); however, after 13 months of continuous fluconazole therapy, lymphadenomegaly worsened and samples were collected for culture and antifungal susceptibility. The Histoplasma capsulatum isolate had a very high fluconazole minimum inhibitory concentration (MIC) of 64 µg/ml and an itraconazole MIC of 0.06 µg/ml. The owner declined a change to itraconazole and, ultimately, the cat developed neurologic signs and was euthanized. Owing to the initial response to fluconazole followed by treatment failure and high MIC value, acquired fluconazole resistance was suspected. Clinical breakpoints for fluconazole for the dimorphic fungi are not available to define true antifungal resistance. Relevance and novel information This is the first published report of reduced susceptibility to fluconazole in a cat being treated for histoplasmosis. Fluconazole failure and increases in MIC between pretreatment and long-term treatment isolates are known to occur in humans with histoplasmosis. Practitioners should be aware of this possibility when treating cats with fluconazole (particularly in cases with long-term [>1 year] fluconazole therapy or in cases with disease recrudescence)