Technique of open rotator cuff repair.

With current surgical techniques, open rotator cuff repair can provide significant functional improvement and pain relief in the majority of patients. Important principles include performing anterior acromioplasty, bursal resection, rotator cuff mobilization, tension-free repair to the greater tuberosity with nonabsorbable sutures, and meticulous deltoid repair. In massive rotator cuff tears, the coracoacromial ligament should be repaired to prevent anterosuperior instability, and partial repair of the rotator cuff is recommended over performing transfer procedures. Postoperative rehabilitation requires the patient to avoid active exercises for 6 weeks and weights for 3 months. With these techniques, 85% to 90% satisfactory results can be expected.

Modulation of the production of cytokines in titanium-stimulated human peripheral blood monocytes by pharmacological agents. The role of cAMP-mediated signaling mechanisms.

Cytokines secreted by activated macrophages play a role in the development of osteolysis adjacent to prosthetic joints. To determine whether the synthesis of cytokines can be inhibited by pharmacological agents, we studied the role of the cAMP-protein kinase A signal transduction pathway in the synthesis of interleukin-6 and tumor necrosis factor-alpha and examined the effect of potential pharmacological regulators of this pathway in human peripheral blood monocytes stimulated with titanium particles. Dibutyryl cAMP enhanced the synthesis of interleukin-6 by titanium-stimulated monocytes and resulted in a marked increase (maximum, seventyfold) in the synthesis of interleukin-6 even in the absence of titanium particles. However, the active analogs (agonists) of cAMP, dibutyryl cAMP and Sp cAMP, inhibited the production of tumor necrosis factor-alpha by titanium-stimulated monocytes (the maximum effects resulted in complete inhibition), while the cAMP antagonist, Rp cAMP, enhanced the production of tumor necrosis factor-alpha. Additional agents that alter the intracellular levels of cAMP were examined for their effects on the synthesis of cytokines. Prostaglandins E1 and E2 were potent inhibitors of the synthesis of tumor necrosis factor-alpha but stimulated the synthesis of interleukin-6. In contrast, indomethacin enhanced the stimulatory effects of titanium particles on tumor necrosis factor-alpha, resulting in a more than threefold increase in the maximum levels of tumor necrosis factor-alpha. Phosphodiesterase inhibitors, such as isobutyryl methylxanthine and pentoxifylline, which increase intracellular levels of cAMP, caused a decrease in the production of tumor necrosis factor-alpha and an increase in the production of interleukin-6. In contrast, the fluoroquinolone antibiotic ciprofloxacin, which is also a phosphodiesterase inhibitor, caused a dose-dependent inhibition of the synthesis of both tumor necrosis factor-alpha and interleukin-6 by titanium-stimulated monocytes, suggesting that ciprofloxacin suppresses the synthesis of interleukin-6 through a mechanism that is independent of cAMP.

Increased levels of tumor necrosis factor-alpha and interleukin-6 protein and messenger RNA in human peripheral blood monocytes due to titanium particles.

Cytokines produced by macrophages in the periprosthetic membranes surrounding joint replacements have been implicated as causal agents in osteolysis and prosthetic loosening. The present study characterizes the response of human peripheral blood monocytes to titanium particles. Monocytes were obtained from volunteers and blood that had been donated to the American Red Cross and were cultured in the presence of titanium particles (one to three micrometers in diameter). There were consistent dose-dependent increases in the production of TNF-alpha (tumor necrosis factor-alpha) and IL-6 (interleukin-6) protein, with the greatest stimulation generally observed with a concentration of 6 x 10(5) to 6 x 10(6) particles of titanium per milliliter. The level of TNF-alpha was the greatest (fifty to 1000 times greater than the control level) after eight hours of exposure to titanium particles; the level of IL-6 was two to five times greater than the control level after sixteen hours of exposure. These increases were similar to those observed after stimulation with lipopolysaccharide and depended on de novo synthesis rather than on release from intracellular stores. The production of TNF-alpha was inhibited in a dose-dependent manner by the translational inhibitor cycloheximide and the transcriptional inhibitor actinomycin D, indicating the requirement for both mRNA (messenger RNA) and protein synthesis for the induction of cytokine synthesis by titanium particles. Although the increase in the levels of cytokine mRNA in response to titanium was rapid (thirty to ninety minutes), the increase in the level of TNF-alpha mRNA preceded that of IL-6 mRNA. The level of TNF-alpha mRNA was the greatest at ninety minutes and the level of IL-6 mRNA was the greatest at three hours. After stimulation with titanium particles, the level of TNF-alpha mRNA was increased as much as fivefold and the level of IL-6 mRNA, as much as twelvefold.