Human bronchial epithelial and endothelial cells express alpha7 nicotinic acetylcholine receptors.

The epithelial or endothelial cells that line the human bronchi and the aorta express nicotinic acetylcholine receptors (nAChRs) of alpha3 subtypes. We report here that human bronchial epithelial cells (BEC) and aortic endothelial cells (AEC) express also the nAChR alpha7 subunit, which forms functional nAChRs. Polymerase chain reaction and in situ hybridization experiments detected alpha7 subunit mRNA in cultured human BEC and AEC and in sections of rat trachea. The binding of radiolabeled alpha-bungarotoxin revealed a few thousand binding sites per cell in cultured human BEC and human and bovine AEC. Western blot and immunohistochemistry experiments demonstrated that cultured BEC and AEC express a protein(s) recognized by anti-alpha7 antibodies. Whole-cell patch-clamp studies of cultured human BEC demonstrated the presence of fast-desensitizing currents activated by choline and nicotine that were blocked reversibly by methyllycaconitine (1 nM) and irreversibly by alpha-bungarotoxin (100 nM), consistent with the expression of functional alpha7 nAChRs. In some cells, choline activated also slowly decaying currents, confirming previous reports that BEC express functional alpha3beta4 nAChRs. Exposure of cultured BEC to nicotine (1 microM) for 3 days up-regulated functional alpha7 and alpha3 nAChRs, as indicated by the increased number of cells responding to acetylcholine and choline, with both fast-desensitizing currents, which were blocked irreversibly by alpha-bungarotoxin, and with slowly desensitizing currents, which are alpha-bungarotoxin-insensitive currents. The presence of alpha7 nAChRs in BEC and AEC suggests that some toxic effects of tobacco smoke could be mediated through these nicotine-sensitive receptors.     

Lumbar diskogenic pain, provocation diskography, and imaging correlates

Diskogenic pain refers to pain mediated by the intrinsic innervation of the intervertebral disk. It is experienced as pain centered at the symptomatic spine segment (axial pain) without radicular features or radiculopathy. There is no pathoanatomic gold standard; histologic examination cannot identify a painful disk. The current reference standard for diskogenic pain is provocation diskography. This article reviews diskogenic pain, the history of provocation diskography, and its current use in the diagnosis of lumbar diskogenic pain. The extensive literature describing imaging features which may predict a positive diskogram, and allow non-invasive diagnosis of diskogenic pain, is examined.     

Intravertebral clefts opacified during vertebroplasty: pathogenesis,technical implications,and prognostic significance

BACKGROUND AND PURPOSE: Intravertebral clefts have long been considered as pathognomonic for avascular necrosis and as a rare cause of compression fracture. We have observed unsuspected clefts opacifying frequently during vertebroplasty. Our purpose in this study was to determine the incidence of these clefts in symptomatic osteoporotic compression fractures, assess the sensitivity of MR imaging and conventional radiography in the detection of these clefts, and determine whether there is any prognostic significance of these clefts in patients treated with vertebroplasty. METHODS: Retrospective chart reviews were conducted of 135 vertebroplasty procedures performed during a 2-year period. MR images and conventional radiographs were reviewed for the presence of clefts defined as fluid-filled cavities on MR images or gas-filled cavities on conventional radiographs. Digital radiographs obtained at the time of the procedure were inspected for the presence of opacified clefts. Imaging findings were correlated with subjective pain scores documented before the procedure and at 1 week, 1 month, 6 months, and 12 months after vertebroplasty. RESULTS: Two hundred thirty-six osteoporotic compression fractures were treated with polymethylmethacrylate in 125 patients. Thirty-one and eight-tenths percent of the fractures were noted to contain clefts at the time of vertebroplasty. Fluid-filled clefts were detected on preoperative MR images in only 52.8% of the fractures with opacified clefts at vertebroplasty. Gas-filled clefts were evident on preoperative conventional radiographs in only 11.4% of the fractures with opacified clefts at vertebroplasty. No significant difference was noted in numerical pain scores between the two populations at baseline or 1 week or 1 month after the procedure. Pain scores at 6 and 12 months after vertebroplasty showed a trend toward greater pain relief in patients with clefts, although the difference was not statistically significant. A sustained, statistically significant decrease in pain scores after treatment (P <.01) was noted in both groups. CONCLUSION: Intravertebral clefts are much more common than previously described and probably represent fracture nonunions. Imaging is not sensitive in detecting these clefts before vertebroplasty. We advocate complete filling of the cleft with cement during vertebroplasty to maximize stabilization of the fracture fragments. There is a trend toward greater pain relief being achieved 6 and 12 months after the procedure in patients with clefts that are opacified at the time of vertebroplasty.     

A comparative study of 3 different cartilage repair techniques

Purpose  

The value of cell-free techniques in the treatment of cartilage defects remains under debate. In this study, cartilage repair of full-thickness chondral defects in the knees of Goettinger minipigs was assessed by treatment with a cell-free collagen type-I gel or a collagen type-I gel seeded with autologous chondrocytes. As a control, abrasion arthroplasty was included.     

Painful metastases involving bone: percutaneous image-guided cryoablation--prospective trial interim analysis

PURPOSE: To prospectively determine the safety and effectiveness of percutaneous cryoablation for the reduction of pain, improvement in the activities of daily life, and reduction in the use of analgesic medications for patients with painful metastatic lesions involving bone. MATERIALS AND METHODS: This study was compliant with HIPAA and was approved by the institutional review board. Written informed consent was obtained. During 18 months, 14 patients (eight men, six women; age range, 21-72 years; mean age, 54 years) with one or two painful metastatic lesions involving bone, with a score of 4 or greater out of 10 for worst pain in a 24-hour period, and who did not respond to or refused conventional radiation treatment or chemotherapy were treated with percutaneous cryoablation. Patient response was measured with the Brief Pain Inventory, and analgesic use was recorded before and after the procedure at days 1 and 4, weekly for 4 weeks, and then every other week for a total of 6 months. Complications were monitored. Analysis of the primary end points was undertaken with paired comparison procedures by using paired t tests across individual time points supplemented with repeated measures analysis of variance. RESULTS: Treated lesions were 1-11 cm in diameter. Before cryoablation, the mean score for worst pain in a 24-hour period was 6.7 of 10; the score decreased to 3.8 (P = .003) 4 weeks after treatment. Mean pain interference with activities of daily living was 5.5 of 10 before treatment and decreased to 3.2 (P = .004) 4 weeks after treatment. All eight (100%) patients (exact 95% binomial confidence interval: 63%, 100%) for whom narcotics were prescribed prior to the procedure reported a reduction in these medications after cryoablation. No serious complications were observed. CONCLUSION: Percutaneous cryoablation is a safe and effective method for palliation of pain due to metastatic disease involving bone.     

Frequency of Discordance between Facet Joint Activity on Technetium Tc99m Methylene Diphosphonate SPECT/CT and Selection for Percutaneous Treatment at a Large Multispecialty Institution

BACKGROUND AND PURPOSE:The clinical impact of facet joint bone scan activity is not fully understood. The hypothesis of this study is that facet joints targeted for percutaneous treatment in clinical practice differ from those with reported activity on technetium Tc99m methylene diphosphonate SPECT/CT.MATERIALS AND METHODS:All patients with a technetium Tc99m methylene diphosphonate SPECT/CT scan of the lumbar or cervical spine who underwent subsequent percutaneous facet joint steroid injection or comparative medial branch blocks at our institution between January 1, 2008, and February 19, 2013, were identified. Facet joints with increased activity were compared with those treated. A chart review characterized the clinical reasons for treatment discrepancies.RESULTS:Of 74 patients meeting inclusion criteria, 52 (70%) had discrepant imaging findings and treatment selection of at least 1 facet joint, whereas 34 patients (46%) had a side (right vs left) discrepancy. Only 92 (70%) of 132 facet joints with increased activity were treated, whereas 103 (53%) of 195 of treated facet joints did not have increased activity. The most commonly documented clinical rationale for discrepancy was facet joint activity that was not thought to correlate with clinical findings, cited in 18 (35%) of 52 patients.CONCLUSIONS:Facet joints undergoing targeted percutaneous treatment were frequently discordant with those demonstrating increased technetium Tc99m methylene diphosphonate activity identified by SPECT/CT at our institution, in many cases because the active facet joint(s) did not correlate with clinical findings. Further prospective double-blinded investigations of the clinical significance of facet joint activity by use of technetium Tc99m methylene diphosphonate SPECT/CT and comparative medial branch blocks are needed.

Clinical examination and anatomic imaging do not reliably identify specific painful facet joints.^1–3 Prior studies suggest that technetium Tc99m methylene diphosphonate (^99mTc MDP) bone scan activity can predict if a facet joint is painful and if there will be a positive response to percutaneous intervention targeted specifically to active facet joints.^4–6 These prior studies used strict treatment of every facet joint with increased radiotracer activity on bone scan,^4–6 concluding that ^99mTc MDP SPECT can decrease the number of treated facet joints.⁴ However, those results can only be applicable if this is used in clinical practice and is feasible. Moreover, these studies did not incorporate CT scan for facet joint localization, use comparative medial branch blocks for diagnosis, include clearly blinded patients and proceduralists, or examine the impact of ^99mTc MDP bone scan results in actual clinical practice. Such shortcomings limit the conclusions of these prior reports and indicate the need for further examination of the clinical usefulness of ^99mTc MDP facet joint activity. In addition, evaluation of the impact of imaging in actual practice is important because the efficacy demonstrated in clinical studies often does not translate into true clinical effectiveness when the ideal rigorous methods of the efficacy study are no longer applied.⁷ That is, the effect of real-life variables such as clinical findings suggesting facet joint pain on a specific side or level and the variability of physician experience and philosophy should be evaluated to confirm or refute the impact of controlled studies on actual clinical practice and to identify areas in need of future investigation.In our anecdotal experience, the specific facet joints referred for percutaneous facet joint intervention are sometimes widely discordant from those with reported activity on ^99mTc MDP SPECT/CT. Specifically, we have seen some patients with suspected facetogenic pain where the ^99mTc MDP SPECT/CT scan does not seem to demonstrate concordant facet joint activity in the location or even on the side of pain. We have also observed that many facet joints with bone scan activity do not seem to correlate with a clinical facet joint pain syndrome. However, the concordance of facet joint bone scan activity and targeted facet joint treatment in actual clinical practice is not well described. Furthermore, the clinical rationale for imaging-procedural discrepancy is not known.The hypothesis of this study is that facet joints that are targeted for percutaneous treatment in clinical practice differ from those with reported activity on ^99mTc MDP SPECT/CT scans.