The Effects of Hyperbaric Oxygen on Rheumatoid Arthritis: A Pilot Study.

BACKGROUND/OBJECTIVE: This case series pilot study assessed the effects of hyperbaric oxygen therapy (HBO2) for treating rheumatoid arthritis (RA). METHODS: Ten RA subjects received 30 HBO2 treatments over 6 to 10 weeks. Serial rheumatologic evaluations (ie, the Disease Activity Scale [DAS28], the Routine Assessment of Patient Index Data 3, and the Pain and Sleep Quality Questionnaire) were completed at baseline, throughout the course of the study, and at the 6-month follow-up. RESULTS: There was a statistically significant effect of HBO2 therapy over time on the DAS28-Global Health (p = 0.01), the DAS28-C-reactive protein (p = 0.002), and the DAS28-erythrocyte sedimentation rate (p = 0.008) measures; these analyses excluded 2 patients who were in clinical remission at baseline. Selected post hoc comparisons showed significantly lower DAS28-Global Health, DAS28-C-reactive protein, and DAS28-erythrocyte sedimentation rate scores at 3 and 6 months relative to baseline. In addition, statistically significant decreases in pain as measured by the Routine Assessment of Patient Index Data 3 and Pain and Sleep Quality Questionnaire were observed at the end of HBO2 relative to baseline. CONCLUSIONS: Hyperbaric oxygen therapy is effective for joint pain in patients with RA based on data from multiple, validated clinical measures. Further research with more subjects and the use of a control group is necessary.

Approach to Osteoarthritis Management for the Primary Care Provider.

Osteoarthritis is the most common joint disease in the world today. Patients will present for evaluation and treatment to primary care providers on a regular basis. A general understanding of its pathogenesis, risk factors, diagnosis, and treatment is imperative. The goal of this article was to provide the primary care provider with a primer on osteoarthritis care and management.

Role of Leukocyte-Platelet-Rich Fibrin in Endoscopic Endonasal Skull Base Surgery Defect Reconstruction.

Objective Advancements in endoscopic endonasal approaches have increased the extent and complexity of skull base resections, in turn demanding the development of novel techniques for skull base defect reconstruction. The objective of this pilot study was to investigate the effect of leukocyte-platelet-rich fibrin (L-PRF) on the postoperative healing after endoscopic skull base surgery. Methods Between January and May of 2015, 47 patients underwent endoscopic endonasal resection of sellar, parasellar, and suprasellar lesions with the application of L-PRF membranes during the skull base reconstruction at two surgical centers. Early postoperative records were retrospectively reviewed. Results We found that 21 days following the surgery, 17/41 patients (42%) demonstrated improvement in the crusting score as compared with their 7 day postoperative examination. Ten of these patients (23%) showed no crusting. Fourteen (34%) patients had no change in the crusting score. Six patient records were incomplete. A total of 4/47 cases (8.5%) had postoperative cerebrospinal fluid leak requiring surgical repair. Conclusion This study demonstrates the potential utility of L-PRF membranes for skull base defect reconstruction. Future studies will be conducted to better assess the role of L-PRF in endoscopic skull base surgery.

Pain improvement in rheumatoid arthritis with hyperbaric oxygen: report of three cases.

Rheumatoid arthritis (RA) is a chronic, erosive, symmetrical inflammatory disease that can progress to synovial destruction, severe disability and premature mortality. Immunotherapies, while beneficial, can cause significant adverse events. Three patients with RA treated in our facility with hyperbaric oxygen (HBO2) for unrelated diagnoses all reported significant but unanticipated improvement in RA-related pain, increased activity and improved sleeping patterns. Two improved while continuing traditional RA medications; the other patient had all RA meds held due to cancer and postoperative wound healing problems. The significant symptomatic improvement in these three patients led us to hypothesize that HBO2 for patients with RA may result in decreased joint pain, increased activity level, improvement in sleeping patterns and possibly a decreased need for standard rheumatologic medications, effectively reducing or avoiding the effects of immunosuppression. A clinical trial is planned to objectively assess these findings.

Rash and elevated creatine kinase in a deployed soldier.

A 24-year-old active duty soldier was evacuated from Afghanistan to the United States after persistent upper respiratory tract infection. His course was complicated by an exfoliative rash, diffuse muscle aches, and elevated creatine kinase following trimethoprim-sulfamethoxazole exposure that persisted despite withdrawal of the medication. Dermatomyositis was strongly considered, but the patient had a negative muscle biopsy and had positive serologies for acute Epstein-Barr virus infection. We present a case of acute Epstein-Barr virus infection and possible trimethoprim-sulfamethoxazole reaction mimicking dermatomyositis.

Tumor necrosis factor-alpha stimulation of calcitonin gene-related peptide expression and secretion from rat trigeminal ganglion neurons.

Expression of the neuropeptide calcitonin gene-related peptide (CGRP) in trigeminal ganglion is implicated in neurovascular headaches and temporomandibular joint disorders. Elevation of cytokines contributes to the pathology of these diseases. However, a connection between cytokines and CGRP gene expression in trigeminal ganglion nerves has not been established. We have focused on the effects of the cytokine tumor necrosis factor-alpha (TNF-alpha). TNFR1 receptors were found on the majority of CGRP-containing rat trigeminal ganglion neurons. Treatment of cultures with TNF-alpha stimulated CGRP secretion. In addition, the intracellular signaling intermediate from the TNFR1 receptor, ceramide, caused a similar increase in CGRP release. TNF-alpha caused a coordinate increase in CGRP promoter activity. TNF-alpha treatment activated the transcription factor NF-kappaB, as well as the Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways. The importance of TNF-alpha induction of MAP kinase pathways was demonstrated by inhibiting MAP kinases with pharmacological reagents and gene transfer with an adenoviral vector encoding MAP kinase phosphatase-1 (MKP-1). We propose that selective and regulated inhibition of MAP kinases in trigeminal neurons may be therapeutically beneficial for inflammatory disorders involving elevated CGRP levels.

Regulation of the cell-specific calcitonin/calcitonin gene-related peptide enhancer by USF and the Foxa2 forkhead protein.

An 18-bp enhancer controls cell-specific expression of the calcitonin/calcitonin gene-related peptide gene. The enhancer is bound by a heterodimer of the bHLH-Zip protein USF-1 and -2 and a cell-specific factor from thyroid C cell lines. In this report we have identified the cell-specific factor as the forkhead protein Foxa2 (previously HNF-3beta). Binding of Foxa2 to the 18-bp enhancer was demonstrated using electrophoretic mobility shift assays. The cell-specific DNA-protein complex was selectively competed by a series of Foxa2 DNA binding sites, and the addition of Foxa2 antiserum supershifted the complex. Likewise, a complex similar to that seen with extracts from thyroid C cell lines was generated using an extract from heterologous cells expressing recombinant Foxa2. Interestingly, overexpression of Foxa2 activated the 18-bp enhancer in heterologous cells but only in the presence of the adjacent helix-loop-helix motif. Likewise, coexpression of USF proteins with Foxa2 yielded greater activation than by Foxa2 alone. Unexpectedly, Foxa2 overexpression repressed activity in the CA77 thyroid C cell line, suggesting that Foxa2 may interact with additional cofactors. The stimulatory role of Foxa2 at the calcitonin/calcitonin gene-related peptide gene enhancer was confirmed by short interfering RNA-mediated knockdown of Foxa2. As seen with Foxa2 overexpression, the effect of Foxa2 knockdown also required the adjacent helix-loop-helix motif. These results provide the first evidence for combinatorial control of gene expression by bHLH-Zip and forkhead proteins.

Dopamine D2-like antagonists induce chromatin remodeling in striatal neurons through cyclic AMP-protein kinase A and NMDA receptor signaling.

Antipsychotic drugs regulate gene transcription in striatal neurons by blocking dopamine D2-like receptors. Little is known about the underlying changes in chromatin structure, including covalent modifications at histone N-terminal tails that are epigenetic regulators of gene expression. We show that treatment with D2-like antagonists rapidly induces the phosphorylation of histone H3 at serine 10 and the acetylation of H3-lysine 14 in bulk chromatin from striatum and in nuclei of striatal neurons. We find that, in vivo, D2-like antagonist-induced H3 phospho-acetylation is inhibited by the NMDA receptor antagonist MK-801 and by the protein kinase A (PKA) inhibitor Rp-adenosine 3c',5c'-cyclic monophosphorothioate triethylammonium salt but increased by the PKA activator Sp-adenosine 3c',5c'-cyclic monophosphorothioate triethylammonium salt. Furthermore, in dissociated striatal cultures which lack midbrain and cortical pre-synaptic inputs, H3 phospho-acetylation was induced by glutamate, L-type Ca2+ channel agonists and activators of cAMP-dependent PKA but inhibited by NMDA receptor antagonists or PKA antagonists. The dual modification, H3pS10-acK14, was enriched at genomic sites with active transcription and showed the kinetics of the early response. Together, these results suggest that histone modifications and chromatin structure in striatal neurons are dynamically regulated by dopaminergic and glutamatergic inputs converging on the cellular level. Blockade of D2-like receptors induces H3 phospho-acetylation, H3pS10-acK14, through cAMP-dependent PKA, and post-synaptic NMDA receptor signaling.