Establishing a common language for lumbar transforaminal epidural steroid injections.

BACKGROUND: Patients presenting to spine surgeons for lumbar radiculopathy often undergo initial conservative treatment including medications, therapy, and lumbar transforaminal epidural steroid injections. Despite a growing number of spinal injections performed, there is a lack of available data regarding the occurrence of wrong-site injections. However, when examined, the discrepancies between ordering level and level of epidural steroid injection performed are immense. To aid with this issue, we propose that instead of ordering a lumbar transforaminal epidural steroid injections at a given level, it should be ordered to address a specific nerve root with laterality. This has the potential to reduce wrong-site procedures and improve patient outcomes. METHODS: Retrospective chart review of 60 patients at a private orthopaedic spine practice under the care of spine surgeons or physician assistants over a 1-year period. The progress note, injection order form, procedure note, and procedural fluoroscopy were reviewed. If there were inconsistencies between one or more of these steps, it was deemed a failure. Results were analyzed to assess for any differences in outcomes between the two groups. We calculated our sample size prior to the study and powered it at 90%; descriptive statistics, Chi-square, Fisher's exact test, Student's t-test, and Wilcoxon rank sum tests were used where appropriate utilizing SAS v9.4. RESULTS: Thirty-seven patients (37/60, 61.6%) were considered a failure. There were no failures when ordering an S1 nerve root injection. We identified one wrong-site procedure and one wrong-level order that was identified and corrected by the interventionalist. CONCLUSIONS: There were multiple inconsistencies identified at various steps in the injection ordering process. This indicates a need to standardize the language used in this process to avoid wrong-site procedures. There were no inconsistencies in ordering an S1 injection, likely because this injection could only be ordered at the nerve root. It is also critical to utilize and save a localization film to ensure accuracy and accountability. We propose indicating the affected nerve root in all cases rather than the level of disc pathology would avoid confusion.

Intractable Central Pain in a Patient With Diffuse Glioma.

Central neuropathic pain can be difficult to treat and, subsequently, cause a great amount of disability and distress to patients, which limits quality of life. Common etiologies include the following: stroke, spinal cord injury, multiple sclerosis, infection, vasculitis, and malignancy. This case is a description of an 18-yr-old male patient diagnosed with a grade IV diffuse glioma who experienced severe neuropathic pain refractory to first-line treatment options including the following: gabapentinoids, tricyclic antidepressants, and selective serotonin and norepinephrine reuptake inhibitors. The patient remained on high-dose oral gabapentin as well as methadone and high-dose oxycodone for pain control at the time of submission. The aims of this case report were to review the nociceptive pathways and to explore the role of opioids in central neuropathic pain secondary to neoplasm because a better understanding of these topics can aid physiatrists in better taking care of these patients and improving function and quality of life.

Antioxidant and pro-oxidant mechanisms of (+) catechin in microsomal CYP2E1-dependent oxidative stress.

The objectives of this work were to evaluate the effects of catechin on cytochrome P450 2E1 (CYP2E1)-dependent oxidative stress. Microsomes co-expressing human CYP2E1 with NADPH cytochrome P450 reductase and cytochrome b5 were incubated with NADPH and DTPA at pH 7.0. Superoxide anion generation was specifically detected by spin-trapping with DEPMPO. Generation of the DEPMPO-OOH adduct was not observed in the absence of CYP2E1 and in the presence of superoxide dismutase (SOD) or catechin, while catalase was ineffective. Reactive oxygen species generation was detected with 1-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine (CPH) by the EPR-detection of its oxidation product, 3-carboxy-proxyl radical (CP●). CP● generation was not observed in the absence of CYP2E1 and in the presence of SOD, while catalase was ineffective. In contrast, catechin increased CPH oxidation, an effect that was not observed in the absence of CYP2E1 or in the presence of SOD (but not catalase), and was not associated with an increase in oxygen consumption. Catechin also increased the non-specific oxidation of the probes CPH and hydroethidine by the superoxide anion-generating system xanthine plus xanthine oxidase. Catechin oxidized CPH in the presence of horseradish peroxidase plus hydrogen peroxide, a catechin radical-generating system. In conclusion, catechin exhibits both antioxidant (superoxide-scavenging) and pro-oxidant effects under CYP2E1-dependent oxidative stress.

Single-molecule visualization of fast polymerase turnover in the bacterial replisome.

The Escherichia coli DNA replication machinery has been used as a road map to uncover design rules that enable DNA duplication with high efficiency and fidelity. Although the enzymatic activities of the replicative DNA Pol III are well understood, its dynamics within the replisome are not. Here, we test the accepted view that the Pol III holoenzyme remains stably associated within the replisome. We use in vitro single-molecule assays with fluorescently labeled polymerases to demonstrate that the Pol III* complex (holoenzyme lacking the ß2 sliding clamp), is rapidly exchanged during processive DNA replication. Nevertheless, the replisome is highly resistant to dilution in the absence of Pol III* in solution. We further show similar exchange in live cells containing labeled clamp loader and polymerase. These observations suggest a concentration-dependent exchange mechanism providing a balance between stability and plasticity, facilitating replacement of replisomal components dependent on their availability in the environment.

Pseudomyogenic hemangioendothelioma.

Pseudomyogenic hemangioendothelioma (PMHE) is a rare vascular tumor that was added to the World Health Organization classification of soft tissue tumors. These tumors have a unique clinical presentation and microscopic appearance as compared to other vascular tumors in the differential diagnosis. Unlike its microscopic mimicker epithelioid sarcoma, PMHE rarely metastasizes and long-term survival in affected patients is excellent. In this report, we present a patient with PMHE and review the current literature on clinical presentation and histologic differentiation of this unique tumor, comparing findings to its mimickers.

Effects of Rho Kinase Inhibitors on Intraocular Pressure and Aqueous Humor Dynamics in Nonhuman Primates and Rabbits.

PURPOSE: This study examines the effects of 2 Rho kinase inhibitors on intraocular pressure (IOP) and aqueous humor dynamics. METHODS: IOPs of New Zealand albino rabbits with ocular normotension and cynomolgus macaques (nonhuman primate, NHP) with chronic unilateral laser-induced glaucoma were measured at baseline and periodically after a 9 a.m. dose of H-1152, Y-27632, or vehicle. In a separate group of NHPs, aqueous flow, outflow facility, uveoscleral outflow, and IOP were determined after treatment with Y-27632 or vehicle control. RESULTS: Decreases in IOP were found in rabbits (n = 5) at 6 h after one dose of 2% Y-27632 (29%, P = 0.0002) or 1% H-1152 (35%, P = 0.0001), and in hypertensive eyes of NHPs (n = 7-9) at 3 h after one dose of 2% Y-27632 (35%, P = 0.005) or 1% H-1152 (51%, P = 0.0003). With 2 doses of 1% Y-27632 or vehicle in NHP hypertensive eyes (n = 12), significant drug effects were IOP reduction of 28% (P = 0.05) at 2.5 h after the second dose and increases in aqueous flow (36%; P = 0.013), uveoscleral outflow (59%, P = 0.008), and outflow facility (40%; P = 0.01). In normotensive eyes of the same animals, aqueous flow increased by 21% (P = 0.03). No significant change was found in any of the other parameters. CONCLUSIONS: Y-27632 and H-1152 lower IOP in rabbits and hypertensive eyes of NHPs for at least 6 h after single doses. The Y-27632 effect on IOP in hypertensive NHP eyes is caused by increases in outflow facility and uveoscleral outflow. An increase in aqueous humor formation attenuates but does not prevent an IOP decrease.

Introduction to microperimetry and its use in analysis of geographic atrophy in age-related macular degeneration.

PURPOSE OF REVIEW: This article discusses recent advances in the fundus-guided perimetry (microperimetry) and its utilization in evaluation and monitoring of patients with geographic atrophy. RECENT FINDINGS: Although best-corrected visual acuity has been gold standard in clinical practice for decades, it does not provide an entire assessment of visual function that determines daily activity and quality of life of a patient. Furthermore, psychophysical tests, including low-luminance visual acuity, reading speed, and contrast sensitivity, cannot be used to quantify retinal sensitivity or detect pattern of retinal dysfunction. Microperimetry provides a true evaluation of visual function by offering fundus-controlled testing through eye-tracking technology that allows for structural and functional correlation and test-retest reliability for the same test point. Furthermore, it enables precise assessment of location and stability of fixation. Recent research has shown microperimetry to be more representative of the macular function in macular diseases. SUMMARY: Microperimetry is currently the clinical investigation of choice to assess residual visual functions and functional vision in macular degenerative diseases, especially geographic atrophy. There is an increasing popularity to employ microperimetry in clinical trials investigating new treatments for geographic atrophy, as well as other macular degenerative diseases, as a reliable functional outcome measure.

Proofreading exonuclease on a tether: the complex between the E. coli DNA polymerase III subunits α, epsilon, θ and ß reveals a highly flexible arrangement of the proofreading domain.

A complex of the three (αεθ) core subunits and the ß2 sliding clamp is responsible for DNA synthesis by Pol III, the Escherichia coli chromosomal DNA replicase. The 1.7 Å crystal structure of a complex between the PHP domain of α (polymerase) and the C-terminal segment of ε (proofreading exonuclease) subunits shows that ε is attached to α at a site far from the polymerase active site. Both α and ε contain clamp-binding motifs (CBMs) that interact simultaneously with ß2 in the polymerization mode of DNA replication by Pol III. Strengthening of both CBMs enables isolation of stable αεθ:ß2 complexes. Nuclear magnetic resonance experiments with reconstituted αεθ:ß2 demonstrate retention of high mobility of a segment of 22 residues in the linker that connects the exonuclease domain of ε with its α-binding segment. In spite of this, small-angle X-ray scattering data show that the isolated complex with strengthened CBMs has a compact, but still flexible, structure. Photo-crosslinking with p-benzoyl-L-phenylalanine incorporated at different sites in the α-PHP domain confirm the conformational variability of the tether. Structural models of the αεθ:ß2 replicase complex with primer-template DNA combine all available structural data.

A direct proofreader-clamp interaction stabilizes the Pol III replicase in the polymerization mode.

Processive DNA synthesis by the αεθ core of the Escherichia coli Pol III replicase requires it to be bound to the ß2 clamp via a site in the α polymerase subunit. How the ε proofreading exonuclease subunit influences DNA synthesis by α was not previously understood. In this work, bulk assays of DNA replication were used to uncover a non-proofreading activity of ε. Combination of mutagenesis with biophysical studies and single-molecule leading-strand replication assays traced this activity to a novel ß-binding site in ε that, in conjunction with the site in α, maintains a closed state of the αεθ-ß2 replicase in the polymerization mode of DNA synthesis. The ε-ß interaction, selected during evolution to be weak and thus suited for transient disruption to enable access of alternate polymerases and other clamp binding proteins, therefore makes an important contribution to the network of protein-protein interactions that finely tune stability of the replicase on the DNA template in its various conformational states.