CalDAG-GEFI down-regulation in the striatum as a neuroprotective change in Huntington's disease.

Huntingtin protein (Htt) is ubiquitously expressed, yet Huntington's disease (HD), a fatal neurologic disorder produced by expansion of an Htt polyglutamine tract, is characterized by neurodegeneration that occurs primarily in the striatum and cerebral cortex. Such discrepancies between sites of expression and pathology occur in multiple neurodegenerative disorders associated with expanded polyglutamine tracts. One possible reason is that disease-modifying factors are tissue-specific. Here, we show that the striatum-enriched protein, CalDAG-GEFI, is severely down-regulated in the striatum of mouse HD models and is down-regulated in HD individuals. In the R6/2 transgenic mouse model of HD, striatal neurons with the largest aggregates of mutant Htt have the lowest levels of CalDAG-GEFI. In a brain-slice explant model of HD, knock-down of CalDAG-GEFI expression rescues striatal neurons from pathology induced by transfection of polyglutamine-expanded Htt exon 1. These findings suggest that the striking down-regulation of CalDAG-GEFI in HD could be a protective mechanism that mitigates Htt-induced degeneration.

Does the public think it is reasonable to wait for more evidence before funding innovative health technologies? The case of PET scanning in Ontario.

OBJECTIVES: Many innovative health technologies do not have a sufficient evidence-base to allow for adequate assessment of their benefits. Funders in several countries have been exploring arrangements that allow for temporary or partial coverage of these technologies, but only as part of a further evaluation. The public's support of arrangements that restrict access to innovative technology until sufficient evidence is available is crucial if these arrangements are going to remain viable. The project's other objective is to examine the lay public's views on a case in which patients' publicly funded access to an innovative health technology is being delayed until there is sufficient evidence to justify a coverage decision. The case considered is the Ontario (Canada) government's decision to restrict access to positron emission tomography (PET) scans until further evidence becomes available. METHODS: The case was deliberated on by twenty-six members of the Toronto Health Policy Citizens' Council, with a follow-up survey administered to individual council members. RESULTS: The majority of council members agreed that the approach taken by the government was reasonable and in the best interests of its citizens. The council did express concerns regarding certain aspects of the case, including about the length of time it is taking to obtain further evidence. CONCLUSIONS: Public support for arrangements that limit access to new technologies will likely vary depending on the details of the specific arrangement being proposed. Deliberative public dialogue can be effectively used to identify cases the general public is most likely to support.

Survey of Ehlers-Danlos Patients' ophthalmic surgery experiences.

BACKGROUND: Ehlers-Danlos Syndrome (EDS) is a rare disease affecting approximately 1 in 5,000 people. Although ophthalmic conditions associated with EDS have been described, little data exist concerning ophthalmic surgical outcomes experienced by EDS patients. METHODS: Patients with EDS were surveyed via the EDS Society and asked about their ophthalmic surgical experiences including procedure, complications, and the timing with respect to receiving the EDS diagnosis. Complications were confirmed as such by subspecialists. RESULTS: Of 579 respondents, 467 reported confirmed EDS, and 112 of those had an ophthalmic procedure, including refractive surgery, cataract/lens surgery, retinal surgery, strabismus surgery, oculoplastic surgery, corneal surgery, and laser surgery for glaucoma. The rate of confirmed complications was: 23%-refractive, 33%-lens/cataract, 33%-retina, 59%-strabismus, 23%- oculoplastics, 0%-cornea, and 25%-glaucoma laser. In addition, 76% of patients underwent surgery prior to the EDS diagnosis. CONCLUSIONS: Patients with EDS may have elevated risk of postoperative ophthalmic surgical complications. It would seem reasonable to systemically and prospectively explore how patients with EDS respond to ophthalmic surgery. Furthermore, it would seem circumspect to ask surgical candidates patients about whether they carry a diagnosis of EDS or have signs and symptoms of EDS prior to surgery.

Orbital Floor Fracture with Atypical Extraocular Muscle Entrapment Pattern and Intraoperative Asystole in an Adult.

Extraocular muscle entrapment in a nondisplaced orbital fracture, although a well-known entity in pediatric trauma, is atypical in adults. It can present with a triad of bradycardia, nausea, and in rare cases, syncope, and result in severe fibrosis of damaged and incarcerated muscle. We present a case of muscle entrapment in a partially nondisplaced two-wall orbital fracture with accompanying preoperative bradycardia and intraoperative asystole in an adult.