Reliability of MRI findings in candidates for lumbar disc prosthesis

Introduction: Limited reliability data exist for localised magnetic resonance imaging (MRI) findings relevant to planning of treatment with lumbar disc prosthesis and later outcomes. We assessed the reliability of such findings in chronic low back pain patients who were accepted candidates for disc prosthesis. Methods: On pretreatment MRI of 170 patients (mean age 41 years; 88 women), three experienced radiologists independently rated Modic changes, disc findings and facet arthropathy at L3/L4, L4/L5 and L5/S1. Two radiologists rerated 126 examinations. For each MRI finding at each disc level, agreement was analysed using the kappa statistic and differences in prevalence across observers using a fixed effects model. Results: All findings at L3/L4 and facet arthropathy at L5/S1 had a mean prevalence <10% across observers and were not further analysed, ensuring interpretable kappa values. Overall interobserver agreement was generally moderate or good (kappa 0.40–0.77) at L4–S1 for Modic changes, nucleus pulposus signal, disc height (subjective and measured), posterior high-intensity zone (HIZ) and disc contour, and fair (kappa 0.24) at L4/L5 for facet arthropathy. Posterior HIZ at L5/S1 and severely reduced subjective disc height at L4/L5 differed up to threefold in prevalence between observers (p< 0.0001). Intraobserver agreement was mostly good or very good (kappa 0.60–1.00). Conclusion: In candidates for disc prosthesis, mostly moderate interobserver agreement is expected for localised MRI findings

Thoracic costotransverse joint pain patterns: a study in normal volunteers

<p>Abstract</p> <p>Background</p> <p>Pain referral patterns of asymptomatic costotransverse joints have not been established. The objective of this study was to determine the pain referral patterns of asymptomatic costotransverse joints via provocative intra-articular injection.</p> <p>Methods</p> <p>Eight asymptomatic male volunteers received a combined total of 21 intra-articular costotransverse joint injections. Fluoroscopic imaging was used to identify and isolate each costotransverse joint and guide placement of a 25 gauge, 2.5 inch spinal needle into the costotransverse joint. Following contrast medium injection, the quality, intensity, and distribution of the resultant pain produced were recorded.</p> <p>Results</p> <p>Of the 21 costotransverse joint injections, 16 (76%) were classified as being intra-articular via arthrograms taken at the time of injection, and 14 of these injections produced a pain sensation distinctly different from that of needle placement. Average pain produced was 3.3/10 on a 0–10 verbal pain scale. Pain was described generally as a deep, dull ache, and pressure sensation. Pain patterns were located superficial to the injected joint, with only the right T2 injections showing referred pain 2 segments cranially and caudally. No chest wall, upper extremity or pseudovisceral pains were reported.</p> <p>Conclusion</p> <p>This study provides preliminary data of the pain referral patterns of costotransverse joints. Further research is needed to compare these findings with those elicited from symptomatic subjects.</p

Prevalence of facet joint pain in chronic spinal pain of cervical, thoracic, and lumbar regions

BACKGROUND: Facet joints are a clinically important source of chronic cervical, thoracic, and lumbar spine pain. The purpose of this study was to systematically evaluate the prevalence of facet joint pain by spinal region in patients with chronic spine pain referred to an interventional pain management practice. METHODS: Five hundred consecutive patients with chronic, non-specific spine pain were evaluated. The prevalence of facet joint pain was determined using controlled comparative local anesthetic blocks (1% lidocaine or 1% lidocaine followed by 0.25% bupivacaine), in accordance with the criteria established by the International Association for the Study of Pain (IASP). The study was performed in the United States in a non-university based ambulatory interventional pain management setting. RESULTS: The prevalence of facet joint pain in patients with chronic cervical spine pain was 55% 5(95% CI, 49% – 61%), with thoracic spine pain was 42% (95% CI, 30% – 53%), and in with lumbar spine pain was 31% (95% CI, 27% – 36%). The false-positive rate with single blocks with lidocaine was 63% (95% CI, 54% – 72%) in the cervical spine, 55% (95% CI, 39% – 78%) in the thoracic spine, and 27% (95% CI, 22% – 32%) in the lumbar spine. CONCLUSION: This study demonstrated that in an interventional pain management setting, facet joints are clinically important spinal pain generators in a significant proportion of patients with chronic spinal pain. Because these patients typically have failed conservative management, including physical therapy, chiropractic treatment and analgesics, they may benefit from specific interventions designed to manage facet joint pain

Down-Regulation of Yes Associated Protein 1 Expression Reduces Cell Proliferation and Clonogenicity of Pancreatic Cancer Cells

BACKGROUND: The Hippo pathway regulates organ size by inhibiting cell proliferation and promoting cell apoptosis upon its activation. The Yes Associated Protein 1 (YAP1) is a nuclear effector of the Hippo pathway that promotes cell growth as a transcription co-activator. In human cancer, the YAP1 gene was reported as amplified and over-expressed in several tumor types. METHODS: Immunohistochemical staining of YAP1 protein was used to assess the expression of YAP1 in pancreatic tumor tissues. siRNA oligonucleotides were used to knockdown the expression of YAP1 and their effects on pancreatic cancer cells were investigated using cell proliferation, apoptosis, and anchorage-independent growth assays. The Wilcoxon signed-rank, Pearson correlation coefficient, Kendall's Tau, Spearman's Rho, and an independent two-sample t (two-tailed) test were used to determine the statistical significance of the data. RESULTS: Immunohistochemistry studies in pancreatic tumor tissues revealed YAP1 staining intensities were moderate to strong in the nucleus and cytoplasm of the tumor cells, whereas the adjacent normal epithelial showed negative to weak staining. In cultured cells, YAP1 expression and localization was modulated by cell density. YAP1 total protein expression increased in the nuclear fractions in BxPC-3 and PANC-1, while it declined in HPDE6 as cell density increased. Additionally, treatment of pancreatic cancer cell lines, BxPC-3 and PANC-1, with YAP1-targeting siRNA oligonucleotides significantly reduced their proliferation in vitro. Furthermore, treatment with YAP1 siRNA oligonucleotides diminished the anchorage-independent growth on soft agar of pancreatic cancer cells, suggesting a role of YAP1 in pancreatic cancer tumorigenesis. CONCLUSIONS: YAP1 is overexpressed in pancreatic cancer tissues and potentially plays an important role in the clonogenicity and growth of pancreatic cancer cells

Minimizing the source of nociception and its concurrent effect on sensory hypersensitivity: An exploratory study in chronic whiplash patients

Abstract. Background. The cervical zygapophyseal joints may be a primary source of pain in up to 60% of individuals with chronic whiplash associated disorders (WAD) and may be a contributing factor for peripheral and centrally mediated pain (sensory hypersensitivity). Sensory hypersensitivity has been associated with a poor prognosis. The purpose of the study was to determine if there is a change in measures indicative of sensory hypersensitivity in patients with chronic WAD grade II following a medial branch block (MBB) procedure in the cervical spine. Methods. Measures of sensory hypersensitivity were taken via quantitative sensory testing (QST) consisting of pressure pain thresholds (PPT's) and cold pain thresholds (CPT's). In patients with chronic WAD (n = 18), the measures were taken at three sites bilaterally, pre- and post- MBB. Reduced pain thresholds at remote sites have been considered an indicator of central hypersensitivity. A healthy age and gender matched comparison group (n = 18) was measured at baseline. An independent t-test was applied to determine if there were any significant differences between the WAD and normative comparison groups at baseline with respect to cold pain and pressure pain thresholds. A dependent t-test was used to determine whether there were any significant differences between the pre and post intervention cold pain and pressure pain thresholds in the patients with chronic WAD. Results. At baseline, PPT's were decreased at all three sites in the WAD group (p < 0.001). Cold pain thresholds were increased in the cervical spine in the WAD group (p < 0.001). Post-MBB, the WAD group showed significant increases in PPT's at all sites (p < 0.05), and significant decreases in CPT's at the cervical spine (p < 0.001). Conclusions. The patients with chronic WAD showed evidence of widespread sensory hypersensitivity to mechanical and thermal stimuli. The WAD group revealed decreased sensory hypersensitivity following a decrease in their primary source of pain stemming from the cervical zygapophyseal joints

Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

SummaryWe describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers

Where learning and teaching meet : heuristics and the information processing model : an honors thesis (HONRS 499)

There is no abstract available for this thesisThesis (B.?.)Honors Colleg