Ocular developmental disorders, including the group classified as microphthalmia, anophthalmia, and coloboma (MAC) and inherited retinal dystrophies, collectively represent leading causes of hereditary blindness. Characterized by extreme genetic and clinical heterogeneity, the separate groups share many common genetic causes, in particular relating to pathways controlling retinal and retinal pigment epithelial maintenance. To understand these shared pathways and delineate the overlap between these groups, we investigated the genetic cause of an autosomal dominantly inherited condition of retinal dystrophy and bilateral coloboma, present in varying degrees in a large, five-generation family. By linkage analysis and exome sequencing, we identified a previously undescribed heterozygous mutation, n.37C > T, in the seed region of microRNA-204 (miR-204), which segregates with the disease in all affected individuals. We demonstrated that this mutation determines significant alterations of miR-204 targeting capabilities via in vitro assays, including transcriptome analysis. In vivo injection, in medaka fish (Oryzias latipes), of the mutated miR-204 caused a phenotype consistent with that observed in the family, including photoreceptor alterations with reduced numbers of both cones and rods as a result of increased apoptosis, thereby confirming the pathogenic effect of the n.37C > T mutation. Finally, knockdown assays in medaka fish demonstrated that miR-204 is necessary for normal photoreceptor function. Overall, these data highlight the importance of miR-204 in the regulation of ocular development and maintenance and provide the first evidence, to our knowledge, of its contribution to eye disease, likely through a gain-of-function mechanism.
Background Anti-epileptic drug (AED) prophylaxis in the first-seven days post-traumatic brain injury (TBI) is known to reduce seizure frequency acutely. AED efficacy is equivalent; therefore, choice of AED may rest with their side-effects. We hypothesise that AEDs that impair balance will prolong recovery, shown by a longer hospital stay. We compared length of hospital stay (and reported dizziness) in TBI patients receiving the commonest AEDs used in our TBI patients, Phenytoin (which may cause imbalance), and Levetiracetam (which does not affect balance). Method A retrospective observational study was performed on TBI patients admitted to a Major Trauma Unit between October 2013 and June 2018. 100 of 278 patients treated with phenytoin or levetiracetam monotherapy for seizure prophylaxis were included. The inclusion criteria of admission Glasgow Coma Score of 14 or more and length of stay less than 3 weeks minimised confounding variables such as non-ambulant patients. Length of hospital stay and incidence of dizziness were assessed. Results The length of hospital stay was longer for patients on Phenytoin versus Levetiracetam, i.e., 10.74 vs. 7.58 days (p = 0.015; unpaired, two-sided t test). Dizziness reported by patients on phenytoin was 24% and levetiracetam was 8% (p = 0.018; Chi-squared test). Conclusion In this cohort, using Phenytoin for acute TBI, seizure prophylaxis was associated with longer length of stay and more dizziness compared to Levetiracetam. Given their equivalent AED efficacy in acute TBI seizure prophylaxis, our data suggest that Levetiracetam is preferable to Phenytoin for early seizure prophylaxis in TBI. This requires evaluation in larger, prospective studies.
Objectives12% of patients with severe Traumatic brain injury (TBI) suffer from seizures. Evidence suggests that the use of an antiepileptic drug (AED) is beneficial in preventing early post TBI seizures. To date, no specific NICE guidelines exist on the choice of post TBI seizure prophylaxis. This study aims to identify the trend in AED usage, the impact on length of stay and to compare the tolerability of phenytoin and levetiracetam.DesignRetrospective observational study.Subjects201 patients.MethodsAll patients admitted to a Major Trauma Unit following a head injury treated with levetiracetam or phenytoin for seizure prophylaxis were included in the study. Data was collected between October 2013 – September 2014 and November 2016 – October 2017. Patient demographics, Glasgow Coma Score (GCS) on admission, length of treatment, AED toxicity, length of stay, complications, surgical input and length of ITU stay were recorded.Results85.6% of patients were treated with phenytoin in 2013–2014% and 82.5% were treated with levetiracetam in 2016–2017. The average length of stay for phenytoin was 23.2 days and 13.9 days for levetiracetam. Subgroup analysis was performed on patients with an admission GCS of 14–15. Length of stay for phenytoin was 14.9 days (SD −11.87) and levetiracetam 9.4 days (SD 10.588) (p=0.07). 24% of patients on phenytoin and 14% on levetiracetam suffered from dizziness.ConclusionsThis suggests that levetiracetam is tolerated better with fewer side effects. We recommend its use in clinical practice.
BackgroundAlemtuzumab is an effective disease modifying treatment (DMT) for people with relapsing multiple sclerosis (pwRMS). Its mechanism of action includes profound lymphocyte depletion.ObjectiveTo analyse the pattern of lymphocyte depletion and associated infections after alemtuzumab administration in a cohort of pwRMS treated at our centre.MethodspwRMS treated with alemtuzumab were identified on our clinical record system (Cerner Millennium). Baseline blood results, total lymphocyte counts (TLC) and infections post-treatment were studied.Results84 pwMS on alemtuzumab were followed up for a mean of 8.7 months. One month after the first treatment cycle, TLC was 13% of baseline (from 2.2 to 0.28 × 109/l). TLC recovered to >0.6 by month 3 and to >1 by month 9, however remained below baseline in all pwRMS. After the 2nd treatment cycle, TLC reconstitution was more rapid, to >1×109/l within six months. 19 (23%) pwRMS had infections within four months of treatment cycles. Infections affected the respiratory tract in 7 (8%) pwRMS, and the urinary tract in 9 (11%). All but one infection occurred with TLC <0.6.ConclusionInfections are common in pwRMS treated with alemtuzumab. To reduce their incidence prophylactic antibiotics should be considered in pwRMS with TLC of <0.6×109/l.
We report a case of a previously well, 25-year-old Caucasian female whose diagnosis of multiple sclerosis (MS) followed significant trauma. Her symptoms and signs developed quickly and satisfied the criteria for rapidly evolving relapsing-remitting MS. She was started on natalizumab (Tysabri) and was stabilized. We discuss the existing literature on traumatic demyelination and possible underlying mechanisms.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.