Timothy M. Simon

Articular cartilage: injury pathways and treatment options.

Articular cartilage injury and degeneration is a frequent occurrence in synovial joints. Treatment of these articular cartilage lesions are a challenge because this tissue is incapable of quality repair and/or regeneration to its native state. Nonoperative treatments endeavor to control symptoms, and include anti-inflammatory medication, viscosupplementation, bracing, orthotics, and activity modification. Techniques to stimulate the intrinsic repair (fibrocartilage) process include drilling, abrasion, and microfracture of the subchondral bone. Currently, the clinical biologic approaches to treat cartilage defects include autologous chondrocyte implantation, periosteal transfer, and osteochondral autograft or allograft transplantation. Newer strategies employing tissue engineering being studied involve the use of combinations of progenitor cells, bioactive factors, and matrices, and the use of focal synthetic devices. Many new and innovative treatments are being explored in this exciting field. However, there is a paucity of prospective, randomized controlled clinical trials that have compared the various techniques, treatment options, indications and efficacy.

Inhibitory effects of a new oral gold compound on hela cells

Auranofin (AF), a recently introduced oral antirheumatic coordinated gold compound, was investigated for its antitumor potential. Due to certain similarities with the antitumor‐coordinated compound, cis‐Diamminedichloro‐platinum II, we studied the effects of AF on cell proliferation. These studies included assessing DNA, RNA, and protein synthesis as measured by incorporation of 3H‐thymidine, 3H‐uridine, and 3H‐leucine, respectively, into HeLa cells. AF was shown to exert a dose‐dependent inhibition on DNA synthesis and to inhibit 3H‐thymidine uptake more rapidly and persistently than 3H‐uridine or 3H‐leucine uptake at a gold concentration of 75–100 μg/dl. These three parameters were inhibited with a 24‐hour exposure to 100 μg/dl. The inhibition of 3H‐thymidine uptake in HeLa pretreated for 6 hours with 50 or 100 μg/dl of gold was found to be irreversible. No change in tracer uptake was observed in the acid‐soluble pool or in the uptake of 3H‐2‐deoxy‐D‐glucose in these cells. Furthermore, HeLa cells demonstrated marked reductions in viability and oxygen uptake after exposure to AF. Dose‐dependent surface morphological changes, e.g., blebbing, pitting, were noted in these cells after a brief treatment period. These results suggest this coordinated gold compound exerts a significant inhibitory effect on essential biological processes and functions.

Cambium cell stimulation from surgical release of the periosteum

An autograft of periosteal tissue containing cambium cells has potential to become chondrogenic or osteogenic depending on the regeneration repair strategies. The potential number of harvestable cambium cells diminishes with age. Other factors may be associated with a reduction in the number or variable yields of cambium cells including harvest technique, harvest site location, and the time interval from harvest to implantation. Attempts to increase the number of cambium cells have included improvements in harvesting and handling technique, and expansion of the cells in tissue culture. An „in situ”︁ stimulation and proliferation technique would offer the potential for increasing the number of cambium cells in a cost‐effective manner for transplantation without the need for expansion in tissue culture.

Assessment of Immune Response During Chrysotherapy: Comparison of Gold Sodium Thiomalate vs. Auranofin

Auranofin (AF) differs significantly from gold sodium thiomalate (GST) in formulation, i.e., aurous gold is stabilized by dual sulfur and phosphorus ligands, has hydrophobic rather than hydrophilic characteristics, and lacks ionic charge. These attributes facilitate: oral absorption of AF, plasma membrane penetration, increase in intracellular lymphocyte gold concentration and perhaps thereby influence lymphocyte function. AF therapy was observed to affect primarily T rather than B lymphocyte function in 16 RA subjects receiving 6 mg of AF per day for an average of 45 weeks (range 20-74 weeks) compared with GST-treated RA subjects. Lymphocytes from AF-treated subjects manifested prompt and sharp declines in mitogen-induced lymphoproliferative response (LPR); suppressed response to skin testing with dinitrochlorobenzene (DNCB); and blebbing of lymphocyte membranes as shown by scanning electron microscopy. Suppression of LPR with AF was approximately 60% after the first week and 80% after 20 weeks of therapy, contrasting with 0% and 30% for the respective intervals in GST-treated subjects. DNCB skin testing of AF patients, indicated 11 of 14, failed to respond, whereas all GST patients responded. Local or systemic fungal, bacterial and/or opportunistic infections were not encountered. The effect of AF on B cell effector function, e.g., suppression of immunoglobulins and rheumatoid factor titer, was less marked when contrasted with GST therapy in RA subjects, as previously reported.

History of computer-assisted orthopedic surgery (CAOS) in sports medicine.

Computer-assisted orthopedic surgery and navigation applications have a history rooted in the desire to link imaging technology with real-time anatomic landmarks. Although applications are still evolving in the clinical and research setting, computer-assisted orthopedic surgery has already demonstrated in certain procedures its potential for improving the surgeons accuracy, reproducibility (once past the learning curve), and in reducing outlier outcomes. It is also being used as an educational tool to assist less experienced surgeons in interpreting measurements and precision placements related to well defined anatomic landmarks. It also can assist experienced surgeons, in real-time, plan their bony cuts, tunnel placement, and with ligament balancing. Presently, the additional time, the expense to acquire the needed software and hardware, and restricted reimbursement have slowed the widespread use of navigation. Its current applications have been primarily in joint replacement surgery, spine surgery, and trauma. It has not been widely used in the clinical setting for sports medicine procedures. Sports medicine applications such as individualizing tunnel placement in ligament surgery, opening wedge osteotomy with and without accompanying ligament reconstruction, and balancing and tensioning of the ligaments during the procedure (allowing real-time corrections if necessary) are currently being evaluated and being used on a limited clinical basis.