An experimental study comparing percutaneous discectomy with chemonucleolysis

The aim of this study was to assess the macroscopic and microscopic reaction of the intervertebral disc to discectomy with the Automated Nucleotome (Surgical Dynamics, San Leandro, CA), and to compare this with simple trephining of the annulus and with chemonucleolysis. In eight adult sheep, two of four adjacent lumbar discs were randomly incised using the trephine of the Automated Nucleotome, while the remaining levels underwent nuclear excision with the Automated Nucleotome probe. Another four sheep underwent chemonucleolysis at three adjacent lumbar levels. All animals were killed at 6 weeks. The discs that had undergone trephining alone and those treated with the Automated Nucleotome probe had almost identical radiographic and macroscopic changes and showed similarities on microscopic examination. Macroscopically, these discs did not differ from control levels, whereas those treated with chymopapain showed marked changes with a reduction of both nuclear and annular volume. The results of this study suggest that any therapeutic effect of percutaneous discectomy with the Automated Nucleotome is likely to be attributable to the perforation of the annulus alone with the removal of small amounts of nuclear material contributing little, or nothing, to the claimed benefits of the procedure.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A cadaveric study comparing discography, magnetic resonance imaging, histology, and mechanical behavior of the human lumbar disc

The alms of this study were 1) to compare discography And magnetic resonance imaging scanning on cadavar specimens and to correlate these imaging procedures ' by examining all the discs histologically; and 2) to study the extent to which the amplitude of rotational movement in the neutral and flexed position et a certain level correlates with the morph ologic appearance of lhal disc. Twenty-four human lumbar spines were harvested from cadavers between the ages of 19 and 76 years. Each specimen underwent standard radiography, magnetic resonance imaging scanning, discogrBphy, histologic examination, and measurement of axial rotation In a torsion apparatus. For practical reasons, all specimens did not undergo all of the examinations. Not all peripheral anular lesions were detected by diBcography. Histology showed rim lesions of the anterior anulus in te% of discs with normal discography. The overall incidence of anterior and posterior anular tears was greater in discs where larger amplitudes of rotation were observed, To which extent the one is a consequence of the other or vice versa is not clear. Magnetic resonance imaging was found to be less specific than discography. However, it must be emphasized that no axial magnetic rosemaries imaging scans were taken in this study. Discs with significHntly decreased amounts of nuclear material (observed at histology! can still produce normal mfignstic resonance imaging Images. Infolding of the inner layers of the anulus flbrosus 33% anterior, 4% posterior) was a frequently observed feature. © Lippincott-Raven Publishers.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Optimization of allogeneic mesenchymal progenitor cells for posterolateral spinal fusion with posterior instrumentation in sheep

Autologous bone is a finite resource and harvesting is associated with significant morbidity. This study investigated the safety and efficacy of allogeneic mesenchymal progenitor cells (MPCs) delivered via a calcium phosphate carrier to stimulate bone growth in spinal fusion compared to autograft control in an ovine model. MPCs promote early development of spinal fusion equivalent to autologous bone graft in this ovine model. Given the potential for significant clinical problems with autologous grafting consideration must be given to using MPCs in this setting

Conditional pharmacology/toxicology V: ambivalent effects of thiocyanate upon the development and the inhibition of experimental arthritis in rats by aurothiomalate (Myocrysin(R)) and metallic silver

This article discusses the bizarre and contrary effects of thiocyanate, the major detoxication product of hydrogen cyanide inhaled from tobacco smoke or liberated from cyanogenic foods, e.g. cassava. Thiocyanate both (1) promotes inflammatory disease in rats and (2) facilitates the anti-inflammatory action of historic metal therapies based on gold (Au) or silver (Ag) in three models of chronic polyarthritis in rats. Low doses of nanoparticulate metallic silver (NMS) preparations, i.e. zerovalent silver (Ag) administered orally, suppressed the mycobacterial ('adjuvant')-induced arthritis (MIA) in rats. Similar doses of cationic silver, Ag(I), administered orally as silver oxide or soluble silver salts were inactive. By contrast, NMS only inhibited the development of the collagen-induced arthritis (CIA) and pristane-induced arthritis (PIA) in rats when thiocyanate was also co-administered in drinking water. These (a) arthritis-selective and (b) thiocyanate-inducible effects of Ag were also observed in some previous, and now extended, studies with the classic anti-arthritic drug, sodium aurothiomalate (ATM, Myocrisin®) and its silver analogue (STM), administered subcutaneously to rats developing the same three forms of polyarthritis. In the absence of either Ag or ATM, thiocyanate considerably increased the severity of the MIA, CIA and PIA, i.e. acting as a pro-pathogen. Hitherto, thiocyanate was considered relatively harmless. This may not be true in rats/people with immuno-inflammatory stress and concomitant leukocyte activation. Collectively, these findings show how the drug action of a xenobiotic might be determined by the nature (and severity) of the experimental inflammation, as an example of conditional pharmacology. They also suggest that an incipient toxicity, even of normobiotics such as thiocyanate, might likewise be modulated beneficially by well-chosen xenobiotics (drugs, nutritional supplements, etc.), i.e. conditional toxicology (Powanda 1995). Thus, both the disease and the environment may determine (1) the therapeutic action and/or (2) adverse effect(s) of xenobiotics - and even some normobiotics

Long-term imatinib therapy promotes bone formation in CML patients

Copyright © 2007 by American Society of HematologyImatinib inhibits tyrosine kinases important in osteoclast (c-Fms) and osteoblast (PDGF-R, c-Abl) function, suggesting that long term therapy may alter bone homeostasis. To investigate this question, we measured the trabecular bone volume (TBV) in iliac crest bone biopsies taken from CML patients at diagnosis and again following 2-4 years of imatinib therapy. Half the patients (8/17) showed a substantive increase in TBV (> 2 fold), following imatinib therapy, with the TBV in the post treatment biopsy typically surpassing the normal upper limit for the patient's age group. Imatinib treated patients exhibited reduced serum calcium and phosphate levels with hypophosphatemia evident in 53% (9/17) of patients. In vitro, imatinib suppressed osteoblast proliferation and stimulated osteogenic gene expression and mineralised matrix production by inhibiting PDGF receptor function. In PDGF stimulated cultures, imatinib dose dependently inhibited activation of Akt and Crk L. Using pharmacological inhibitors, inhibition of PI3-kinase/Akt activation promoted mineral formation, suggesting a possible molecular mechanism for the imatinib mediated increase in TBV in vivo. Further investigation is required to determine if the increase in TBV associated with imatinib therapy may represent a novel therapeutic avenue for the treatment of diseases that are characterised by generalised bone loss.Stephen Fitter, Andrea L Dewar, Panagiota Kostakis, L. Bik To, Timothy P Hughes, Marion M Roberts, Kevin Lynch, Barrie Vernon-Roberts, and Andrew CW Zannettin

Immunoselected STRO-3(+) mesenchymal precursor cells and restoration of the extracellular matrix of degenerate intervertebral discs: Laboratory investigation

Object: Chronic low-back pain of discal origin is linked strongly to disc degeneration. Current nonsurgical treatments are palliative and fail to restore the disc extracellular matrix. In this study the authors examined the capacity of ovine mesenchymal precursor cells (MPCs) to restore the extracellular matrix of degenerate discs in an ovine model. Methods: Three adjacent lumbar discs of 24 adult male sheep were injected intradiscally with chondroitinase-ABC (cABC) to initiate disc degeneration. The remaining lumbar discs were used as normal controls. Three months after cABC injection, the L3–4 discs of all animals were injected with either a high dose (4 × 106 cells, in 12 sheep) or low dose (0.5 × 106 cells, in 12 sheep) of MPCs suspended in hyaluronic acid (HA). The adjacent L4–5 degenerate discs remained untreated; the L5–6 discs were injected with HA only. The animals were euthanized at 3 or 6 months after MPC injections (6 sheep from each group at each time point), and histological sections of the lumbar discs were prepared. Radiographs and MR images were obtained prior to cABC injection (baseline), 3 months after cABC injection (pretreatment), and just prior to necropsy (posttreatment). Results: Injection of cABC decreased the disc height index (DHI) of target discs by 45%–50%, confirming degeneration. Some recovery in DHI was observed 6 months after treatment in all cABC-injected discs, but the DHI increased to within baseline control values only in the MPC-injected discs. This improvement was accompanied by a reduction in MRI degeneration scores. The histopathology scores observed at 3 months posttreatment for the high-dose MPC–injected discs and at 6 months posttreatment for the low-dose MPC–injected discs were significantly different from those of the noninjected and HA-injected discs (p <0.001) but not from the control disc scores. Conclusions: On the basis of the findings of this study, the authors conclude that the injection of MPCs into degenerate intervertebral discs can contribute to the regeneration of a new extracellular matrix.Peter Ghosh, Robert Moore, Barrie Vernon-Roberts, Tony Goldschlager, Diane Pascoe, Andrew Zannettino, Stan Gronthos, and Silviu Itesc

Recent advances in annular pathobiology provide insights into rim-lesion mediated intervertebral disc degeneration and potential new approaches to annular repair strategies

The objective of this study was to assess the impact of a landmark annular lesion model on our understanding of the etiopathogenesis of IVD degeneration and to appraise current IVD repairative strategies. A number of studies have utilised the Osti sheep model since its development in 1990. The experimental questions posed at that time are covered in this review, as are significant recent advances in annular repair strategies. The ovine model has provided important spatial and temporal insights into the longitudinal development of annular lesions and how they impact on other discal and paradiscal components such as the NP, cartilaginous end plates, zygapophyseal joints and vertebral bone and blood vessels. Important recent advances have been made in biomatrix design for IVD repair and in the oriented and dynamic culture of annular fibrochondrocytes into planar, spatially relevant, annular type structures. The development of hyaluronan hydrogels capable of rapid in situ gelation offer the possibility of supplementation of matrices with cells and other biomimetics and represent a significant advance in biopolymer design. New generation biological glues and self-curing acrylic formulations which may be augmented with slow delivery biomimetics in microcarriers may also find application in the non-surgical repair of annular defects. Despite major advances, significant technical challenges still have to be overcome before the biological repair of this intractable connective tissue becomes a realistic alternative to conventional surgical intervention for the treatment of chronic degenerate IVDs