Nociplastic pain concept,a mechanistic basis for pragmatic approach to fibromyalgia

Clinical Rheumatology - Nociplastic pain (NP), as a mechanistic term, denotes pain arising from altered nociception without clear evidence of tissue or somatosensory damage. Fibromyalgia (FM), a...     

Two sides on the fibromyalgia coin: physical pain and social pain (invalidation)

Clinical Rheumatology - Although fibromyalgia (FM) has been traditionally defined by the extent of physical pain sites alongside other non-pain symptoms, recent evidence has highlighted the...     

In vitro and in vivo evaluation of heparin mediated growth factor release from tissue‐engineered constructs for anterior cruciate ligament reconstruction

Anterior cruciate ligament (ACL) rupture is a common injury often necessitating surgical treatment with graft reconstruction. Due to limitations associated with current graft options, there is interest in a tissue‐engineered substitute for use in ACL regeneration. While they represent an important step in translation to clinical practice, relatively few in vivo studies have been performed to evaluate tissue‐engineered ACL grafts. In the present study, we immobilized heparin onto electrospun polycaprolactone scaffolds as a means of incorporating basic fibroblast growth factor (bFGF) onto the scaffold. In vitro, we demonstrated that human foreskin fibroblasts (HFFs) cultured on bFGF‐coated scaffolds had significantly greater cell proliferation. In vivo, we implanted electrospun polycaprolactone grafts with and without bFGF into athymic rat knees. We analyzed the regenerated ACL using histological methods up to 16 weeks post‐implantation. Hematoxylin and eosin staining demonstrated infiltration of the grafts with cells, and picrosirius red staining demonstrated aligned collagen fibers. At 16 weeks postop, mechanical testing of the grafts demonstrated that the grafts had approximately 30% the maximum load to failure of the native ACL. However, there were no significant differences observed between the graft groups with or without heparin‐immobilized bFGF. While this study demonstrates the potential of a regenerative medicine approach to treatment of ACL rupture, it also demonstrates that in vitro results do not always predict what will occur in vivo. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:229–236, 2015.     

Esthesioneuroblastoma: An Update on the UCLA Experience, 2002–2013

Objectives To profile the clinical presentation and treatment results of esthesioneuroblastomas at the University of California, Los Angeles (UCLA), from 2002 to 2013. Design Retrospective review. Setting Tertiary academic institution. Participants Forty-one patients with esthesioneuroblastomas treated at UCLA. Main Outcome Measures Overall survival (OS) and recurrence-free survival (RFS). Results Thirty-six patients were included with a mean age of 50.1 years and a median duration of follow-up of 33 months. The 5-year RFS and OS were 54% and 82%, respectively. Modified Kadish stage was the only factor identified to affect OS. Multivariate analysis demonstrated that tumor grade was the only factor that had an independent impact on RFS. There was no statistical difference in survival among the surgical approaches chosen. Conclusions The updated data on the UCLA experience reveals that all three surgical approaches chosen provide comparable survival, although longer follow-up will be needed to ascertain if these findings hold true. The endoscopic approach had a statistically significant decrease in length of hospital stay and a trend toward reduced blood loss, intensive care unit admission, and complications. The modified Kadish staging was the only factor identified to predict OS. Multivariate analysis revealed that tumor grade was an independent predictor of recurrence; therefore, its importance should be emphasized in future staging systems.     

Efficacy analysis of hydroxychloroquine therapy in systemic lupus erythematosus: a study on disease activity and immunological biomarkers

Background

Hydroxychloroquine (HCQ) is a widely prescribed medication to patients with systemic lupus erythematosus (SLE), with potential anti-inflammatory effects. This study was performed to investigate the efficacy of HCQ therapy by serial assessment of disease activity and serum levels of proinflammatory cytokines in SLE patients.

Methods

In this prospective cohort study, 41 newly diagnosed SLE patients receiving 400 mg HCQ per day were included. Patients requiring statins and immunosuppressive drugs except prednisolone at doses lower than 10 mg/day were excluded. Outcome measures were assessed before commencement of HCQ therapy (baseline visit) as well as in two follow-up visits (1 and 2 months after beginning the HCQ therapy). Serum samples of 41 age-matched healthy donors were used as controls.

Results

Median levels of IL-1β (p?<?0.001), IL-6 (p?=?0.001), and TNF-α (p?<?0.001) were significantly higher, whereas, median CH50 level was significantly lower (p?<?0.001) in SLE patients compared with controls. Two-month treatment with HCQ resulted in significant decrease in SLEDAI-2K (p?<?0.001), anti-dsDNA (p?<?0.001), IL-1β (p?=?0.003), IL-6 (p?<?0.001) and TNF-α (p?<?0.001) and a significant increase in CH50 levels (p?=?0.012). The reductions in SLEDAI-2K and serum levels of IL-1β and TNF-α were significantly greater in the first month compared with the reductions in the second month.

Conclusion

HCQ therapy is effective on clinical improvement of SLE patients through interfering with inflammatory signaling pathways, reducing anti-DNA autoantibodies and normalizing the complement activity.

     

Differential regulation of observational fear and neural oscillations by serotonin and dopamine in the mouse anterior cingulate cortex

Rationale

The aberrant regulation of serotonin (5-HT) and dopamine (DA) in the brain has been implicated in neuropsychiatric disorders associated with marked impairments in empathy, such as schizophrenia and autism. Many psychiatric drugs bind to both types of receptors, and the anterior cingulate cortex (ACC) is known to be centrally involved with empathy. However, the relationship between the 5-HT/DA system in the ACC and empathic behavior is not yet well known.

Objectives

We investigated the role of 5-HT/DA in empathy-like behavior and in the regulation of ACC neural activity.

Methods

An observational fear learning task was conducted following microinjections of 5-HT, DA, 5-HT and DA, methysergide (5-HT receptor antagonist), SCH-23390 (DA D₁ receptor antagonist), or haloperidol (DA D₂ receptor antagonist) into the mouse ACC. The ACC neural activity influenced by 5-HT and DA was electrophysiologically characterized in vitro and in vivo.

Results

The microinjection of haloperidol, but not methysergide or SCH-23390, decreased the fear response of observing mice. The administration of 5-HT and 5-HT and DA together, but not DA alone, reduced the freezing response of observing mice. 5-HT enhanced delta-band activity and reduced alpha- and gamma-band activities in the ACC, whereas DA reduced only alpha-band activity. Based on entropy, reduced complexity of ACC neural activity was observed with 5-HT treatment.

Conclusions

The current results demonstrated that DA D₂ receptors in the ACC are required for observational fear learning, whereas increased 5-HT levels disrupt observational fear and alter the regularity of ACC neural oscillations.     

Lymphocyte transformation test detects a response to Campylobacter jejuni antigens in patients with Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy. Campylobacter jejuni-associated gastrointestinal infection is identified as a major precipitating agent of GBS; however, a standard test to diagnose this infection in patients with GBS is lacking. The aim of the present study was to evaluate an outer membrane protein (OMP)-based lymphocyte transformation test (LTT) for the diagnosis of C. jejuni infection in GBS. Forty patients with GBS, age and gender matched 52 healthy controls (HC) and 46 disease controls (DC) were analyzed for C. jejuni infection by culture, polymerase chain reaction (PCR) and LTT. Lymphocytes at concentration of 1 × 10⁶/well isolated from GBS patients and controls were stimulated with 20 μg/ml of C. jejuni OMP, and ³H-thymidine was incorporated to measure cell proliferation. LTT detected significantly higher C. jejuni infection compared to culture (77.5 vs. 2.5%; P < 0.05) and PCR (77.5 vs. 22.5%; P < 0.05). The cutoff value of lymphocyte proliferation by receiver operating characteristic (ROC) curve of 2.5 had 77.5% sensitivity and 96.5% specificity. Area under ROC curve was 0.92. The mean SI of the cell proliferation for GBS cases was significantly higher than the controls (GBS vs. HC; P < 0.001, GBS vs. DC; P < 0.001). LTT appears to be a sensitive tool for detecting preceding C. jejuni infection in GBS patients with reasonable sensitivity and specificity. It is possible that the activated lymphocytes might play role in the pathogenesis of neuronal damage in GBS.