Transient Acute Diplopia as a Rare Side Effect of Hydromorphone: A Case Report.

Diplopia, or double vision, has been listed as a rare adverse effect of intravenous hydromorphone, although there are no case studies or literature documenting this. We detail a case of acute transient diplopia correlated with the use of intraoperative hydromorphone and postoperative hydromorphone patient-controlled analgesia. Although the mechanism for this adverse effect is unknown, there may be risk factors that predispose patients to the potential toxic metabolic effects of hydromorphone. We share the first published case of diplopia as a clinically relevant adverse effect of hydromorphone and propose a potential reason behind this association.

Local anesthetic dosing and toxicity of adult truncal catheters: a narrative review of published practice.

BACKGROUND/IMPORTANCE: Anesthesiologists frequently use truncal catheters for postoperative pain control but with limited characterization of dosing and toxicity. OBJECTIVE: We reviewed the published literature to characterize local anesthetic dosing and toxicity of paravertebral and transversus abdominis plane catheters in adults. EVIDENCE REVIEW: We searched the literature for bupivacaine or ropivacaine infusions in the paravertebral or transversus abdominis space in humans dosed for 24 hours. We evaluated bolus dosing, infusion dosing and cumulative 24-hour dosing in adults. We also identified cases of local anesthetic systemic toxicity and toxic blood levels. FINDINGS: Following screening, we extracted data from 121 and 108 papers for ropivacaine and bupivacaine respectively with a total of 6802 patients. For ropivacaine and bupivacaine, respectively, bolus dose was 1.4 mg/kg (95% CI 0.4 to 3.0, n=2978) and 1.0 mg/kg (95% CI 0.18 to 2.1, n=2724); infusion dose was 0.26 mg/kg/hour (95% CI 0.06 to 0.63, n=3579) and 0.2 mg/kg/hour (95% CI 0.06 to 0.5, n=3199); 24-hour dose was 7.75 mg/kg (95% CI 2.1 to 15.7, n=3579) and 6.0 mg/kg (95% CI 2.1 to 13.6, n=3223). Twenty-four hour doses exceeded the package insert recommended upper limit in 28% (range: 17%-40% based on maximum and minimum patient weights) of ropivacaine infusions and 51% (range: 45%-71%) of bupivacaine infusions. Toxicity occurred in 30 patients and was associated with high 24-hour dose, bilateral catheters, cardiac surgery, cytochrome P-450 inhibitors and hypoalbuminemia. CONCLUSION: Practitioners frequently administer ropivacaine and bupivacaine above the package insert limits, at doses associated with toxicity. Patient safety would benefit from more specific recommendations to limit excessive dose and risk of toxicity.

Local anesthetic dosing and toxicity of pediatric truncal catheters: a narrative review of published practice.

BACKGROUND/IMPORTANCE: Despite over 30 years of use by pediatric anesthesiologists, standardized dosing rates, dosing characteristics, and cases of toxicity of truncal nerve catheters are poorly described. OBJECTIVE: We reviewed the literature to characterize dosing and toxicity of paravertebral and transversus abdominis plane catheters in children (less than 18 years). EVIDENCE REVIEW: We searched for reports of ropivacaine or bupivacaine infusions in the paravertebral and transversus abdominis space intended for 24 hours or more of use in pediatric patients. We evaluated bolus dosing, infusion dosing, and cumulative 24-hour dosing in patients over and under 6 months. We also identified cases of local anesthetic systemic toxicity and toxic blood levels. FINDINGS: Following screening, we extracted data from 46 papers with 945 patients.Bolus dosing was 2.5 mg/kg (median, range 0.6-5.0; n=466) and 1.25 mg/kg (median, range 0.5-2.5; n=294) for ropivacaine and bupivacaine, respectively. Infusion dosing was 0.5 mg/kg/hour (median, range 0.2-0.68; n=521) and 0.33 mg/kg/hour (median, range 0.1-1.0; n=423) for ropivacaine and bupivacaine, respectively, consistent with a dose equivalence of 1.5:1.0. A single case of toxicity was reported, and pharmacokinetic studies reported at least five cases with serum levels above the toxic threshold. CONCLUSIONS: Bolus doses of bupivacaine and ropivacaine frequently comport with expert recommendations. Infusions in patients under 6 months used doses associated with toxicity and toxicity occurred at a rate consistent with single-shot blocks. Pediatric patients would benefit from specific recommendations about ropivacaine and bupivacaine dosing, including age-based dosing, breakthrough dosing, and intermittent bolus dosing.

Cylindrical illumination with angular coupling for whole-prostate photoacoustic tomography.

Current diagnosis of prostate cancer relies on histological analysis of tissue samples acquired by biopsy, which could benefit from real-time identification of suspicious lesions. Photoacoustic tomography has the potential to provide real-time targets for prostate biopsy guidance with chemical selectivity, but light delivered from the rectal cavity has been unable to penetrate to the anterior prostate. To overcome this barrier, a urethral device with cylindrical illumination is developed for whole-prostate imaging, and its performance as a function of angular light coupling is evaluated with a prostate-mimicking phantom.

Photoacoustic tomography of intact human prostates and vascular texture analysis identify prostate cancer biopsy targets.

Prostate cancer is poorly visualized on ultrasonography (US) so that current biopsy requires either a templated technique or guidance after fusion of US with magnetic resonance imaging. Here we determined the ability for photoacoustic tomography (PAT) and US followed by texture-based image processing to identify prostate biopsy targets. K-means clustering feature learning and testing was performed on separate datasets comprised of 1064 and 1197 nm PAT and US images of intact, ex vivo human prostates. 1197 nm PAT was found to not contribute to the feature learning, and thus, only 1064 nm PAT and US images were used for final feature testing. Biopsy targets, determined by the tumor-assigned pixels' center of mass, located 100% of the primary lesions and 67% of the secondary lesions. In conclusion, 1064 nm PAT and US texture-based feature analysis provided successful prostate biopsy targets.

Computational Fluid Dynamics of Vascular Disease in Animal Models.

Recent applications of computational fluid dynamics (CFD) applied to the cardiovascular system have demonstrated its power in investigating the impact of hemodynamics on disease initiation, progression, and treatment outcomes. Flow metrics such as pressure distributions, wall shear stresses (WSS), and blood velocity profiles can be quantified to provide insight into observed pathologies, assist with surgical planning, or even predict disease progression. While numerous studies have performed simulations on clinical human patient data, it often lacks prediagnosis information and can be subject to large intersubject variability, limiting the generalizability of findings. Thus, animal models are often used to identify and manipulate specific factors contributing to vascular disease because they provide a more controlled environment. In this review, we explore the use of CFD in animal models in recent studies to investigate the initiating mechanisms, progression, and intervention effects of various vascular diseases. The first section provides a brief overview of the CFD theory and tools that are commonly used to study blood flow. The following sections are separated by anatomical region, with the abdominal, thoracic, and cerebral areas specifically highlighted. We discuss the associated benefits and obstacles to performing CFD modeling in each location. Finally, we highlight animal CFD studies focusing on common surgical treatments, including arteriovenous fistulas (AVF) and pulmonary artery grafts. The studies included in this review demonstrate the value of combining CFD with animal imaging and should encourage further research to optimize and expand upon these techniques for the study of vascular disease.

Label-Free Vibrational Spectroscopic Imaging of Neuronal Membrane Potential.

Detecting membrane potentials is critical for understanding how neuronal networks process information. We report a vibrational spectroscopic signature of neuronal membrane potentials identified through hyperspectral stimulated Raman scattering (SRS) imaging of patched primary neurons. High-speed SRS imaging allowed direct visualization of puff-induced depolarization of multiple neurons in mouse brain slices, confirmed by simultaneous calcium imaging. The observed signature, partially dependent on sodium ion influx, is interpreted as ion interactions on the CH3 Fermi resonance peak in proteins. By implementing a dual-SRS balanced detection scheme, we detected single action potentials in electrically stimulated neurons. These results collectively demonstrate the potential of sensing neuronal activities at multiple sites with a label-free vibrational microscope.

Role of membrane biophysics in Alzheimer's-related cell pathways.

Cellular membrane alterations are commonly observed in many diseases, including Alzheimer's disease (AD). Membrane biophysical properties, such as membrane molecular order, membrane fluidity, organization of lipid rafts, and adhesion between membrane and cytoskeleton, play an important role in various cellular activities and functions. While membrane biophysics impacts a broad range of cellular pathways, this review addresses the role of membrane biophysics in amyloid-ß peptide aggregation, Aß-induced oxidative pathways, amyloid precursor protein processing, and cerebral endothelial functions in AD. Understanding the mechanism(s) underlying the effects of cell membrane properties on cellular processes should shed light on the development of new preventive and therapeutic strategies for this devastating disease.

Nanoparticle-emitted light attenuates amyloid-ß-induced superoxide and inflammation in astrocytes.

Alzheimer's disease (AD) is the sixth leading cause of age-related death with no effective intervention yet available. Our previous studies have demonstrated the potential efficacy of Low Level Laser Therapy (LLLT) in AD cell models by mitigating amyloid-ß peptide (Aß)-induced oxidative stress and inflammation. However, the penetration depth of light is still the major challenge for implementing LLLT in animal models and in the clinical settings. In this study, we present the potential of applying Bioluminescence Resonance Energy Transfer to Quantum Dots (BRET-Qdots) as an alternative near infrared (NIR) light source for LLLT. Our results show that BRET-Qdot-emitted NIR suppresses Aß-induced oxidative stress and inflammatory responses in primary rat astrocytes. These data provide a proof of concept for a nanomedicine platform for LLLT. FROM THE CLINICAL EDITOR: Low Level Laser Therapy has already been demonstrated to mitigate amyloid-ß peptide induced oxidative stress and inflammation, a key driver of Alzheimer's disease. The major issue in moving this forward from cell cultures to live animals and potentially to human subjects is light penetration depth. In this novel study, BRET-Qdots were used as an alternative near infrared light source with good efficacy, paving the way to the development of a nanomedicine platform.

IFITM proteins restrict viral membrane hemifusion.

The interferon-inducible transmembrane (IFITM) protein family represents a new class of cellular restriction factors that block early stages of viral replication; the underlying mechanism is currently not known. Here we provide evidence that IFITM proteins restrict membrane fusion induced by representatives of all three classes of viral membrane fusion proteins. IFITM1 profoundly suppressed syncytia formation and cell-cell fusion induced by almost all viral fusion proteins examined; IFITM2 and IFITM3 also strongly inhibited their fusion, with efficiency somewhat dependent on cell types. Furthermore, treatment of cells with IFN also markedly inhibited viral membrane fusion and entry. By using the Jaagsiekte sheep retrovirus envelope and influenza A virus hemagglutinin as models for study, we showed that IFITM-mediated restriction on membrane fusion is not at the steps of receptor- and/or low pH-mediated triggering; instead, the creation of hemifusion was essentially blocked by IFITMs. Chlorpromazine (CPZ), a chemical known to promote the transition from hemifusion to full fusion, was unable to rescue the IFITM-mediated restriction on fusion. In contrast, oleic acid (OA), a lipid analog that generates negative spontaneous curvature and thereby promotes hemifusion, virtually overcame the restriction. To explore the possible effect of IFITM proteins on membrane molecular order and fluidity, we performed fluorescence labeling with Laurdan, in conjunction with two-photon laser scanning and fluorescence-lifetime imaging microscopy (FLIM). We observed that the generalized polarizations (GPs) and fluorescence lifetimes of cell membranes expressing IFITM proteins were greatly enhanced, indicating higher molecularly ordered and less fluidized membranes. Collectively, our data demonstrated that IFITM proteins suppress viral membrane fusion before the creation of hemifusion, and suggested that they may do so by reducing membrane fluidity and conferring a positive spontaneous curvature in the outer leaflets of cell membranes. Our study provides novel insight into the understanding of how IFITM protein family restricts viral membrane fusion and infection.