Central Retinal Vein Occlusion Associated with Fibromuscular Dysplasia: A Case Report.

In this report, we detail a rare presentation of central retinal vein occlusion (CRVO) in a patient with fibromuscular dysplasia (FMD). A 45-year-old woman with a 12-year history of FMD presented to the ophthalmology clinic with symptoms and exam findings consistent with CRVO. Dilated fundus examination revealed disc edema, diffuse flame, and dot-blot hemorrhages, and tortuous, engorged retinal veins. The patient was diagnosed with CRVO, and she was treated with monthly anti-VEGF monoclonal antibody followed by a VEGF inhibitor. At her most recent follow-up, her macular edema was resolved and her visual acuity had markedly improved. FMD has been shown to rarely present with retinal manifestations, especially in patients with hypertension. This appears to be first case report to document CRVO in the context of known FMD. We suggest that CRVO be considered as a potential complication for young patients with FMD.

Seasonally timed treatment programs for Ascaris lumbricoides to increase impact-An investigation using mathematical models.

There is clear empirical evidence that environmental conditions can influence Ascaris spp. free-living stage development and host reinfection, but the impact of these differences on human infections, and interventions to control them, is variable. A new model framework reflecting four key stages of the A. lumbricoides life cycle, incorporating the effects of rainfall and temperature, is used to describe the level of infection in the human population alongside the environmental egg dynamics. Using data from South Korea and Nigeria, we conclude that settings with extreme fluctuations in rainfall or temperature could exhibit strong seasonal transmission patterns that may be partially masked by the longevity of A. lumbricoides infections in hosts; we go on to demonstrate how seasonally timed mass drug administration (MDA) could impact the outcomes of control strategies. For the South Korean setting the results predict a comparative decrease of 74.5% in mean worm days (the number of days the average individual spend infected with worms across a 12 month period) between the best and worst MDA timings after four years of annual treatment. The model found no significant seasonal effect on MDA in the Nigerian setting due to a narrower annual temperature range and no rainfall dependence. Our results suggest that seasonal variation in egg survival and maturation could be exploited to maximise the impact of MDA in certain settings.

Positron emission tomography and functional characterization of a complete PBR/TSPO knockout.

The evolutionarily conserved peripheral benzodiazepine receptor (PBR), or 18-kDa translocator protein (TSPO), is thought to be essential for cholesterol transport and steroidogenesis, and thus life. TSPO has been proposed as a biomarker of neuroinflammation and a new drug target in neurological diseases ranging from Alzheimer's disease to anxiety. Here we show that global C57BL/6-Tspo(tm1GuWu(GuwiyangWurra))-knockout mice are viable with normal growth, lifespan, cholesterol transport, blood pregnenolone concentration, protoporphyrin IX metabolism, fertility and behaviour. However, while the activation of microglia after neuronal injury appears to be unimpaired, microglia from (GuwiyangWurra)TSPO knockouts produce significantly less ATP, suggesting reduced metabolic activity. Using the isoquinoline PK11195, the ligand originally used for the pharmacological and structural characterization of the PBR/TSPO, and the imidazopyridines CLINDE and PBR111, we demonstrate the utility of (GuwiyangWurra)TSPO knockouts to provide robust data on drug specificity and selectivity, both in vitro and in vivo, as well as the mechanism of action of putative TSPO-targeting drugs.

Synthesis and biological characterisation of 18F-SIG343 and 18F-SIG353, novel and high selectivity σ2 radiotracers, for tumour imaging properties.

BACKGROUND: Sigma2 (σ2) receptors are highly expressed in cancer cell lines and in tumours. Two novel selective 18F-phthalimido σ2 ligands, 18F-SIG343 and 18F-SIG353, were prepared and characterised for their potential tumour imaging properties. METHODS: Preparation of 18F-SIG343 and 18F-SIG353 was achieved via nucleophilic substitution of their respective nitro precursors. In vitro studies including radioreceptor binding assays in the rat brain membrane and cell uptake studies in the A375 cell line were performed. In vivo studies were carried out in mice bearing A375 tumours including positron emission tomography (PET) imaging, biodistribution, blocking and metabolite studies. RESULTS: In vitro studies showed that SIG343 and SIG353 displayed excellent affinity and selectivity for σ2 receptors (Ki(σ2) = 8 and 3 nM, σ2:σ1 = 200- and 110-fold, respectively). The σ2 selectivity of 18F-SIG343 was further confirmed by blocking studies in A375 cells, however, not noted for 18F-SIG353. Biodistribution studies showed that both radiotracers had similar characteristics including moderately high tumour uptake (4%ID/g to 5%ID/g); low bone uptake (3%ID/g to 4%ID/g); and high tumour-to-muscle uptake ratios (four- to sevenfold) up to 120 min. Although radiotracer uptake in organs known to express σ receptors was significantly blocked by pre-injection of competing σ ligands, the blocking effect was not observed in the tumour. PET imaging studies indicated major radioactive localisation in the chest cavity for both ligands, with approximately 1%ID/g uptake in the tumour at 120 min. Metabolite studies showed that the original radiotracers remained unchanged 65% to 80% in the tumour up to 120 min. CONCLUSIONS: The lead ligands showed promising in vitro and in vivo characteristics. However, PET imaging indicated low tumour-to-background ratios. Furthermore, we were unable to demonstrate that uptake in the A375 tumour was σ2-specific. 18F-SIG343 and 18F-SIG343 do not display ideal properties for imaging the σ2 receptor in the A375 tumour model. However, since the radiotracers show promising in vitro and in vivo characteristics, longer scans using appropriate half-life isotopes and alternative tumour models will be carried out in future studies to fully validate the imaging characteristics of these radiotracers.

Effects of hydrocephalus after cerebellar tumor: a case-by-case approach.

Although hydrocephalus affects approximately 80% of children with a posterior fossa tumor, its impact on neurodevelopmental outcomes remains unclear. We investigated the effects of hydrocephalus severity on the development of cognitive, motor, academic, and attention skills in 15 children with cerebellar injury after treatment for a tumor sustained during preschool years. Significant impairment was indicated by scores 2 S.D.s or more below the test norm mean. Results indicated substantial intra-individual and interindividual variation, with little consistent influence of hydrocephalus severity on outcomes. Generally, children with moderate hydrocephalus were least impaired, but the child without hydrocephalus performed most poorly. Those who received a shunt generally performed higher on many of the cognitive, but not motor, tests. Thus, when considering differences within and across individuals, neither hydrocephalus severity nor shunt placement alone is a strong predictor of neurodevelopmental outcomes.

Development of cognitive and motor function following cerebellar tumour injury sustained in early childhood.

We investigated the interrelation between cognitive and motor development and the role of the cerebellum in this relationship by examining performance in each of these domains in 15 children with injury to the cerebellum following tumour before 5 years of age and 242 typically developing control children aged 4-11 years. Each child was given a comprehensive standardised battery of cognitive and motor tests. Results showed depressed levels of performance for the cerebellar patients across both domains at the group level but considerable variation in individual profiles. However, a significant, positive correlation between cognitive and motor skill was found for both the patient and control group, suggesting these domains are developmentally linked. In addition, the effects of several potential moderating variables were explored. Results showed the most reliable predictors of outcome were age at diagnosis and tumour type/treatment. These results suggest that both cognitive and motor skill can be compromised following tumour in the cerebellum in early childhood leading to delayed, but qualitatively typical, development in both domains.