THE BRONCHODILATOR AND CARDIAC STIMULANT EFFECTS OF Th1165a, SALBUTAMOL AND ISOPROTERENOL

ABSTRACT GILES, RALP

White-matter relaxation time and myelin water fraction differences in young adults with autism

Increasing evidence suggests that autism is associated with abnormal white-matter (WM) anatomy and impaired brain ‘connectivity’. While myelin plays a critical role in synchronized brain communication, its aetiological role in autistic symptoms has only been indirectly addressed by WM volumetric, relaxometry and diffusion tensor imaging studies. A potentially more specific measure of myelin content, termed myelin water fraction (MWF), could provide improved sensitivity to myelin alteration in autism. We performed a cross-sectional imaging study that compared 14 individuals with autism and 14 age- and IQ-matched controls. T 1 relaxation times (T 1), T 2 relaxation times (T 2) and MWF values were compared between autistic subjects, diagnosed using the Autism Diagnostic Interview – Revised (ADI-R), with current symptoms assessed using the Autism Diagnostic Observation Schedule (ADOS) and typical healthy controls. Correlations between T 1, T 2 and MWF values with clinical measures [ADI-R, ADOS, and the Autism Quotient (AQ)] were also assessed. Individuals with autism showed widespread WM T 1 and MWF differences compared to typical controls. Within autistic individuals, worse current social interaction skill as measured by the ADOS was related to reduced MWF although not T 1. No significant differences or correlations with symptoms were observed with respect to T 2. Autistic individuals have significantly lower global MWF and higher T 1, suggesting widespread alteration in tissue microstructure and biochemistry. Areas of difference, including thalamic projections, cerebellum and cingulum, have previously been implicated in the disorder; however, this is the first study to specifically indicate myelin alteration in these regions

Subretinal Hyperreflective Material in the Comparison of Age-Related Macular Degeneration Treatments Trials

PurposeTo evaluate the association of subretinal hyperreflective material (SHRM) with visual acuity (VA), geographic atrophy (GA), and scar in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).DesignProspective cohort study within a randomized clinical trial.ParticipantsThe 1185 CATT participants.MethodsMasked readers graded scar and GA on fundus photography and fluorescein angiography and graded SHRM on time-domain and spectral-domain (SD) optical coherence tomography (OCT) throughout 104 weeks. Measurements of SHRM height and width in the fovea, within the center 1 mm(2), or outside the center 1mm(2) were obtained on SD OCT images at 56 (n = 76) and 104 (n = 66) weeks.Main outcome measuresPresence of SHRM, as well as location and size, and associations with VA, scar, and GA.ResultsAmong CATT participants, the percentage with SHRM at enrollment was 77%, decreasing to 68% at 4 weeks after treatment and to 54% at 104 weeks. At 104 weeks, scar was present more often in eyes with persistent SHRM than in eyes with SHRM that resolved (64% vs. 31%; P < 0.0001). Among eyes with detailed evaluation of SHRM at weeks 56 (n = 76) and 104 (n = 66), mean VA letter score was 73.5 (standard error [SE], 2.8), 73.1 (SE, 3.4), 65.3 (SE, 3.5), and 63.9 (SE, 3.7) when SHRM was absent, present outside the central 1 mm(2), present within the central 1 mm(2) but not the foveal center, or present at the foveal center (P = 0.02), respectively. When SHRM was present, the median maximum height under the fovea, within the central 1 mm(2) including the fovea and anywhere within the scan, was 86 μm, 120 μm, and 122 μm, respectively. Visual acuity was decreased with greater SHRM height and width (P < 0.05).ConclusionsIn eyes with neovascular age-related macular degeneration (AMD), SHRM is common and often persists after anti-vascular endothelial growth factor treatment. At 2 years, eyes with scar were more likely to have SHRM than other eyes. Greater SHRM dimensions were associated with worse VA. In eyes with neovascular AMD, SHRM is an important morphologic biomarker