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Background In 2010, wait-times for new patients referred to see a haematologist at our outpatient tertiary care centre clinic exceeded 6 months. The provision of written recommendations for a subset of referred patients was undertaken to reduce patient wait-times. These recommendation letters outlined possible causes of the abnormality for which the patient was being referred and suggested a course of action for follow-up, and patients were then managed by their referring practitioner. We sought to characterize the cohort of patients for whom written recommendations were written and assess whether written recommendations were a satisfactory alternative for the referring practitioner. Methods All haematology patient referrals managed with written recommendations in 2010 were included in the study and were assessed one year later. Referring practitioners who received written recommendations were sent a short survey to evaluate their satisfaction with this process. Results A total of 444 of 2400 referrals were managed with a letter. At 1-year follow-up, 58 (13%, 95% CI) of the abnormalities which prompted the referral had resolved and 201 (45%, 95%CI) had remained stable. There was a single haematology-related death during the 1-year follow-up and the haematological abnormality worsened in 4 (1%) patients. Of 203 (71%) referring practitioners who responded to the satisfaction survey, 90% (95% CI) indicated that they would be satisfied with written recommendations in the future. Interpretation The provision of written recommendations appears to be a safe and satisfactory alternative to an inperson outpatient assessment in certain well-defined subsets of stable outpatients with haematologic abnormalities.

The endocannabinoid, N-arachidonoylethanolamine (AEA), is degraded by the enzyme fatty acid amide hydrolase (FAAH). This study examined whether the FAAH inhibitor, URB597, increases retinal ganglion cell (RGC) survival following optic nerve axotomy in young and aged animals. URB597 alone, or together with either a CB1 or CB2 receptor antagonist, was administered daily for 1 or 2 weeks post-axotomy. Histological assessment of retinas indicated that URB597 increased RGC survival in young retina at 1 and 2 weeks post-axotomy. The increase in RGC survival at 2 weeks was accompanied by a reduction in phagocytic microglia. The CB1 antagonist, AM281, but not the CB2 antagonist, AM630, ablated URB597-mediated RGC neuroprotection. CB1 or CB2 antagonism increased phagocytic microglia in URB597 and vehicle-treated animals. In aged animals, URB597 increased RGC survival at 1 week, but not at 2 weeks post-axotomy and had no effect on microglia. Retinal Iba-1 positive microglia were also decreased in URB597-treated axotomized young animals and this decrease was mitigated by CB1 but not CB2 antagonism. As seen with phagocytotic microglia, the CB2 antagonist, AM630, increased Iba-1 positive microglia in the absence of URB597 treatment. Measurement of retinal endocannabinoid levels in URB597-treated animals at 2 weeks post-axotomy revealed a significant increase in AEA levels, accompanied by a decrease in the AEA metabolite, N-arachidonoyl glycine, in young animals but not aged animals. 2-arachidonoylglycerol levels were similar across all experimental groups. These data demonstrate that URB597-mediated retinal neuroprotective effects are mediated primarily through CB1 receptors and that URB597 neuroprotective efficacy declines with age.

Endothelin-1 (ET-1) is a vasoconstrictor implicated in age-related retinal pathologies. This study determined whether responses to ET-1 differed in retinal arterioles isolated from adult (2–3 months) and aged (>20 months) Fischer 344 rats of both sexes. Risk factors for retinal disease (retinal perfusion pressure, intraocular pressure, blood glucose) were not affected by age. However, sensitivity to ET-1 declined with age, especially in females. Vasoconstrictor responses to 50 mM KCl and Ca2+ release by caffeine (10 mM) were similar in all groups. Retinal ETA and ETB receptor expression also was similar in young and aged rats, regardless of sex. Contractions elicited by 10 nM ET-1 were inhibited by the ETA antagonist BQ-123 (1 μM) in all groups. In contrast, the ETB antagonist BQ-788 (1 μM) restored ET-1-induced contractions in aged female vessels, but had no effect in any other group. Removal of the endothelium also restored contractions in vessels from aged females but not males. Thus, responsiveness to ET-1 declines with age in retinal microvasculature. In males, this is likely mediated by age-related changes in the ETA receptor signaling pathway. By contrast, effects of ET-1 on endothelial ETB receptors attenuate vasoconstrictor responses in aged females.

Monocular deprivation early in development produces considerable change in the organization of connections within the central mammalian visual system. In the dorsal lateral geniculate nucleus, the soma, dendrites, and axon terminal fields of deprived cells become considerably smaller than nondeprived counterparts. We have examined the possibility that subcellular events enabling structural modification of deprived neurons include modification of proteins comprising the cytoskeleton. We examined the integrity of the cytoskeleton by measuring the response of a subset of its proteins to varying durations of monocular deprivation. Loss of all three neurofilament subunits (light, medium, and heavy) within deprived layers was observed to parallel changes in neuron gross structure. Monocular deprivation initiated beyond early life produced neither a change in structure nor a loss of neurofilament labeling.