A Case Report of Antibiotic-Induced Aseptic Meningitis in Psoriasis.

Although frequently prescribed, certain antibiotics such as trimethoprim-sulfamethoxazole carry the risk of a rare yet life-threatening adverse effect, termed drug-induced aseptic meningitis. Morbidity can be avoided if the medication is identified and discontinued. Patients in reported cases tend to be female and have an autoimmune disease or prior adverse reaction to the offending agent. As a rare and poorly characterized condition, the subset of patients using antibiotics at risk for aseptic meningitis remains unclear; hence, cataloging these adverse events remains critical for better elucidating the disease. Here, we report a 62-year-old man with psoriasis and no prior history of sulfa allergy, who presented with a sudden onset of fever, chills, vomiting, and muscle aches 5 hours after taking single doses of trimethoprim-sulfamethoxazole and ciprofloxacin. Common infectious causes were ruled out, and his medications were discontinued. Despite initial symptom resolution with discontinuation, the patient neurologically deteriorated over the next two days before eventually recovering with supportive care. This case highlights the variable presentation of drug-induced aseptic meningitis. In contrast to previous reports of drug-induced aseptic meningitis, our patient was male, older than the median age of 40 years, and did not have a prior adverse reaction to the antibiotic. Furthermore, to the best of our knowledge, we report a possible case of antibiotic-induced aseptic meningitis in a patient with psoriasis. Lastly, the case emphasizes not only the value of a thorough medication history but also the importance of recognizing that patients may deteriorate in the first 48 hours before resolution

Hypoxic–ischemic injury causes functional and structural neurovascular degeneration in the juvenile mouse retina

Abstract Ischemic stroke is a major cause of long-term disabilities, including vision loss. Neuronal and blood vessel maturation can affect the susceptibility of and outcome after ischemic stroke. Although we recently reported that exposure of neonatal mice to hypoxia–ischemia (HI) severely compromises the integrity of the retinal neurovasculature, it is not known whether juvenile mice are similarly impacted. Here we examined the effect of HI injury in juvenile mice on retinal structure and function, in particular the susceptibility of retinal neurons and blood vessels to HI damage. Our studies demonstrated that the retina suffered from functional and structural injuries, including reduced b-wave, thinning of the inner retinal layers, macroglial remodeling, and deterioration of the vasculature. The degeneration of the retinal vasculature associated with HI resulted in a significant decrease in the numbers of pericytes and endothelial cells as well as an increase in capillary loss. Taken together, these findings suggest a need for juveniles suffering from ischemic stroke to be monitored for changes in retinal functional and structural integrity. Thus, there is an emergent need for developing therapeutic approaches to prevent and reverse retinal neurovascular dysfunction with exposure to ischemic stroke

Bayesian and Machine Learning Models for Genomic Prediction of Anterior Cruciate Ligament Rupture in the Canine Model

Anterior cruciate ligament (ACL) rupture is a common, debilitating condition that leads to early-onset osteoarthritis and reduced quality of human life. ACL rupture is a complex disease with both genetic and environmental risk factors. Characterizing the genetic basis of ACL rupture would provide the ability to identify individuals that have high genetic risk and allow the opportunity for preventative management. Spontaneous ACL rupture is also common in dogs and shows a similar clinical presentation and progression. Thus, the dog has emerged as an excellent genomic model for human ACL rupture. Genome-wide association studies (GWAS) in the dog have identified a number of candidate genetic variants, but research in genomic prediction has been limited. In this analysis, we explore several Bayesian and machine learning models for genomic prediction of ACL rupture in the Labrador Retriever dog. Our work demonstrates the feasibility of predicting ACL rupture from SNPs in the Labrador Retriever model with and without consideration of non-genetic risk factors. Genomic prediction including non-genetic risk factors approached clinical relevance using multiple linear Bayesian and non-linear models. This analysis represents the first steps toward development of a predictive algorithm for ACL rupture in the Labrador Retriever model. Future work may extend this algorithm to other high-risk breeds of dog. The ability to accurately predict individual dogs at high risk for ACL rupture would identify candidates for clinical trials that would benefit both veterinary and human medicine

Vigabatrin-Induced Retinal Functional Alterations and Second-Order Neuron Plasticity in C57BL/6J Mice

Purpose: Vigabatrin (VGB) is an effective antiepileptic that increases concentrations of inhibitory γ-aminobutyric acid (GABA) by inhibiting GABA transaminase. Reports of VGB-associated visual field loss limit its clinical usefulness, and retinal toxicity studies in laboratory animals have yielded conflicting results. Methods: We examined the functional and morphologic effects of VGB in C57BL/6J mice that received either VGB or saline IP from 10 to 18 weeks of age. Retinal structure and function were assessed in vivo by optical coherence tomography (OCT), ERG, and optomotor response. After euthanasia, retinas were processed for immunohistochemistry, and retinal GABA, and VGB quantified by mass spectrometry. Results: No significant differences in visual acuity or total retinal thickness were identified between groups by optomotor response or optical coherence tomography, respectively. After 4 weeks of VGB treatment, ERG b-wave amplitude was enhanced, and amplitudes of oscillatory potentials were reduced. Dramatic rod and cone bipolar and horizontal cell remodeling, with extension of dendrites into the outer nuclear layer, was observed in retinas of VGB-treated mice. VGB treatment resulted in a mean 3.3-fold increase in retinal GABA concentration relative to controls and retinal VGB concentrations that were 20-fold greater than brain. Conclusions: No evidence of significant retinal thinning or ERG a- or b-wave deficits were apparent, although we describe significant alterations in ERG b-wave and oscillatory potentials and in retinal cell morphology in VGB-treated C57BL/6J mice. The dramatic concentration of VGB in retina relative to the target tissue (brain), with a corresponding increase in retinal GABA, offers insight into the pathophysiology of VGB-associated visual field loss