Influence of intradiscal medication on nucleus pulposus cells

Background contextEugene Carragee was the first to prove that provocative discography may contribute to intervertebral disc degeneration. Disc degeneration can be induced either by mechanical trauma caused by the puncturing needle or as a pharmacological effect of the drugs instilled into the disc.PurposeThe aim of this study was to test the influence of cortisone, lidocaine, and iopamidol on nucleus pulposus cells under an in vitro setting.Study designControlled in vitro study is the design type.MethodsThe nucleus pulposus was excised from 12 bovine tail intervertebral discs and monolayer cell cultures were generated. The cultures were divided into four sample groups and incubated in either standard cell culture medium (control group) or medium supplemented with the test substances. The dose rate was adapted based on a total dose of 3 mL iopamidol, 1 mL lidocaine, and 10 mg cortisone per nucleus pulposus. Cell count, viability, proliferation, and differentiation features were analyzed. The study was supported by DePuy. No conflicts of interest arise from this support.ResultsAfter 24 hours, a significant decrease in cell counts was observed in all three test groups. Population doubling time was 16 hours in the control group cultured in standard medium and increased to 21 hours (cortisone), 25 hours (iopamidol), and 38 hours (lidocaine) after incubation in discography medication (p<.001). Cell viability was slightly, but not significantly decreased in all medication groups. Cells incubated in Lidocaine were significantly smaller (p<.01) and showed clearly reduced pseudopodia formation. Incubation in lidocaine and iopamidol also significantly reduced glycosaminoglycan synthesis.ConclusionAlthough only a small decrease in cell viability was observed in all three substances tested, cell count and proliferation decreased significantly. Incubation in lidocaine inhibited pseudopodia formation and might therefore interfere with intercellular signalling and cell migration. Glycosaminoglycan synthesis was significantly decreased after contact with lidocaine as well as Iopamidol. These observations suggest that all three medications tested might interfere with biological repair mechanisms of the intervertebral disc and therefore contribute to a further degeneration.     

Racial and ethnic disparities in the use of antipsychotic medication: a systematic review and meta-analysis

Objective

To conduct a systematic review and meta-analysis of published evidence on ethnic or racial disparities in the outpatient use versus non-use of antipsychotics and in the outpatient use of newer versus older antipsychotics.

Method

Electronic databases were searched for potentially relevant studies. Two independent reviewers conducted the review in three stages: title review, abstract review and full-text review. Included studies were those that: (a) report measures of disparity in the outpatient use of antipsychotic drugs in clearly defined racial or ethnic groups (b) have a primary focus on ethnic or racial disparities, and (c) have adjusted for factors known to influence medicine use. Odds ratios were pooled following the inverse-variance method of weighting effect sizes. I ² statistics were calculated to quantify the amount of variation that is likely due to heterogeneity between studies. Funnel plots were produced and Egger’s statistic was calculated to assess potential publication bias.

Results

No significant differences were found in the odds of using any antipsychotics among African Americans (OR = 1.01, CI = 0.99–1.02) compared with non-African Americans and among Latinos (OR = 0.98, CI = 0.86–1.13) compared with non-Latinos. Small to moderate but statistically non-significant disparities were also noted in other ethnic groups: Asians (OR = 1.10, CI = 0.88–1.36), Maoris (OR = 0.78, CI = 0.53–1.13) and Pacific Islanders (OR = 0.97, CI = 0.84–1.11). Among those who received antipsychotic medication, African Americans (OR = 0.62, CI = 0.50–0.78) and Latinos (OR = 0.77, CI = 0.73–0.81) appeared to have lower odds of receiving newer antipsychotics compared with non-African Americans and non-Latinos.

Conclusion

No significant ethnic disparities in the use versus non-use of any antipsychotics were observed, but, among those who received antipsychotic treatment, ethnic minorities were consistently less likely than non-ethnic minorities to be treated with newer antipsychotics.     

Versatile magnetic microdiscs for the radio enhancement and mechanical disruption of glioblastoma cancer cells

This study describes the use of highly versatile, lithographically defined magnetic microdiscs. Gold covered magnetic microdiscs are used in both radiosensitizing cancer cells, acting as intracellular emitters of secondary electrons during radiotherapy, and as well as inducing mechanical damage by exerting a mechanical torque when exposed to a rotating magnetic field. This study reveals that lithographically defined microdiscs with a uniform size of 2 microns in diameter highly increase the DNA damage and reduce the glioblastoma colony formation potential compared to conventional radiation therapy. Furthermore, the addition of mechanical disruption mediated by the magnetic component of the discs increased the efficiency of brain cancer cell killing.

First study demonstrating the use of physically engineered magnetic particles that display two functionalities for cancer treatment.     

Multiplex analysis of genetic polymorphisms within UGT1A9, a gene involved in phase II of Δ9-THC metabolism

We present a novel multiplex assay for the simultaneous detection of 12 polymorphisms within the UGT1A9 sequence, which codes for enzymes involved in phase II biotransformation. The assay combines a multiplexed amplification step with single-base extension sequencing. The method described here is fast, cost-effective, and easy-to-use, combining the relevant features of screening methods for research and diagnostics in pharmacogenetics. To validate the assay, we tested reproducibility and sensitivity and analysed allele frequencies of 110 Caucasian individuals. Furthermore, we describe combining genetic information of individuals consuming Cannabis sativa products with respective plasma concentrations of a metabolite.

     

Validation of the DYALS (dysphagia in amyotrophic lateral sclerosis) questionnaire for the evaluation of dysphagia in ALS patients

Neurological Sciences - Dysphagia is a common symptom during the trajectory of ALS, and it can significantly impact on the quality of life and prognosis of patients. Nowadays, no specific tool for...     

Bilateral autologous microtia reconstruction: a simultaneous two-stage approach

Background

Traditionally, for cases of bilateral autologous ear reconstruction, each side is addressed independently in discrete operative sessions. Herein, we describe our approach to bilateral microtia reconstruction, where each stage is performed simultaneously on both sides.

Methods

All patients who underwent autologous ear reconstruction by a single surgeon (NWB) from April 2006 to January 2012 were retrospectively reviewed. Reconstruction was realized as a two-stage procedure, with each stage performed simultaneously on both sides in bilateral cases. Patient demographics, operative details and incidences of peri- and post-operative complications were collected. A cost comparison of two-stage versus four-stage bilateral auricular reconstruction was completed.

Results

Among a total of 182 patients who underwent autologous ear reconstruction, 18 patients (male, 10, median age, 11.4 years) had simultaneous bilateral auricular correction. Based on estimates derived from unilateral reconstruction theatre times, simultaneous bilateral reconstruction resulted in a savings of 56 min for the first stage and 97 min for the second stage of reconstruction. Moreover, surgical times decreased as operative experience with auricular reconstruction was accrued. There was no increased incidence of peri- or post-operative complications noted. Based on cost estimates at our institution, bilateral reconstruction as a two-stage procedure resulted in a health care cost savings of £10448.16 ($16790.72 USD) per patient with bilateral microtia.

Conclusions

Simultaneous bilateral autologous ear reconstruction is a practicable cost-effective treatment strategy with notable aesthetic and personal benefit to the patient with no increased morbidity.Level of Evidence Level III, therapeutic study.

     

Differences in the vascular tree of the femoral trochlear growth cartilage at osteochondrosis‐susceptible sites in foals revealed by SWI 3T MRI

Focal ischemic chondronecrosis of epiphyseal growth cartilage (EGC) during endochondral ossification is believed to be a key early event on the pathway to osteochondrosis (OC) in both animals and humans. The lateral ridge of the equine trochlea is a site where severe osteochondritis dissecans lesions frequently arise and is a model for the study of naturally occurring disease. Non‐invasive imaging to investigate EGC vascularity may help elucidate why focal ischemia occurs. 3T MRI susceptibility‐weighted imaging (SWI) of femoral trochlea of OC predisposed (n = 10) and control (n = 6) day‐old foals, with minimal joint loading after birth, was performed. SWI and 3D images revealed the EGC vascular architecture without a contrast agent, and matched histologic observations. No vascular lesions were identified. There was no difference in the vascular density and architecture between control and OC specimens, but a striking difference in vascular pattern was seen at the OC‐predilected site in the lateral ridge of the trochlea in all specimens, when compared to the medial ridge of the trochlea, where OC lesions are rarely observed. This site was less ossified with more perichondrial vessels not yet bridging with the subchondral bone. Furthermore, the mean vascular density of all specimens was significantly higher at this site. We speculate that joint morphology and focal internal trauma on this site with a unique vascular architecture may trigger ischemic events at this site. SWI permitted visualization of EGC in young foals with a clinical 3T MRI and paves the way for non‐destructive longitudinal studies to improve understanding of OC in all species. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1539–1546, 2016.