The expression and regulation of nitric oxide synthase in human osteoarthritis-affected chondrocytes: evidence for up-regulated neuronal nitric oxide synthase.

Classically, osteoarthritis (OA) has been considered a noninflammatory disease. However, the detection of selected inflammatory mediators in osteoarthritic fluid, in the absence of significant inflammatory cell infiltrate, is increasingly appreciated. We sought to identify the inflammatory component in human OA-affected cartilage that may be involved in cartilage damage/destruction. Using Western blot analysis and an antibody to the conserved region of nitric oxide synthase (NOS), we have observed up-regulation of NOS, one of the "key players" of inflammation, in chondrocytes of OA-affected patients. Remarkably, none of the cartilage samples examined from normal joints demonstrated detectable amounts of this NOS. Western blot analysis using the same alpha-NOS antibody indicated that this NOS from OA-affected cartilage (OA-NOS) was larger in size than (and distinct from) transfected human hepatocyte or murine inducible NOS (iNOS) (150 versus 133 kD) and similar in size to neuronal constitutive NOS (ncNOS). Antibodies specific for iNOS showed binding to murine and human iNOS but not to OA-NOS, endothelial constitutive NOS, or ncNOS. Antibodies specific for ncNOS bound to ncNOS and also to OA-NOS, but not to murine or human iNOS or endothelial constitutive NOS. Incubation of OA cartilage in serum-free medium resulted in spontaneous release, for up to 72 h, of substantial amounts of nitrite (up to approximately 80 microM/100 mg wet tissue), which could be inhibited by at least 80% with various inhibitors of iNOS, including inhibitors of protein synthesis and transcription factor NF-kappa B, but which (unlike murine macrophage iNOS) was not sensitive to hydrocortisone or TGF-beta. Exposure of OA-affected cartilage to interleukin 1 beta, tumor necrosis factor-alpha, and lipopolysaccharide resulted in approximately 20-50% augmentation of nitrite accumulation, which was also sensitive to cycloheximide and pyrrolidine dithiocarbamate. Hence, our data indicate that OA-NOS (based on immunoreactivity and molecular weight) is similar to ncNOS and that it releases nitric oxide, which may contribute to the inflammation and pathogenesis of cartilage destruction in OA.

Superinduction of cyclooxygenase-2 activity in human osteoarthritis-affected cartilage. Influence of nitric oxide.

Cartilage specimens from osteoarthritis (OA)-affected patients spontaneously released PGE2 at 48 h in ex vivo culture at levels at least 50-fold higher than in normal cartilage and 18-fold higher than in normal cartilage + cytokines + endotoxin. The superinduction of PGE2 production coincides with the upregulation of cyclooxygenase-2 (COX-2) in OA-affected cartilage. Production of both nitric oxide (NO) and PGE2 by OA cartilage explants is regulated at the level of transcription and translation. Dexamethasone inhibited only the spontaneously released PGE2 production, and not NO, in OA-affected cartilage. The NO synthase inhibitor HN(G)-monomethyl-L-arginine monoacetate inhibited OA cartilage NO production by > 90%, but augmented significantly (twofold) the spontaneous production of PGE2 in the same explants. Similarly, addition of exogenous NO donors to OA cartilage significantly inhibited PGE2 production. Cytokine + endotoxin stimulation of OA explants increased PGE2 production above the spontaneous release. Addition of L-NMMA further augmented cytokine-induced PGE2 production by at least fourfold. Inhibition of PGE2 by COX-2 inhibitors (dexamethasone or indomethacin) or addition of exogenous PGE2 did not significantly affect the spontaneous NO production. These data indicate that human OA-affected cartilage in ex vivo conditions shows (a) superinduction of PGE2 due to upregulation of COX-2, and (b) spontaneous release of NO that acts as an autacoid to attenuate the production of the COX-2 products such as PGE2. These studies, together with others, also suggest that PGE2 may be differentially regulated in normal and OA-affected chondrocytes.

Anticoagulant treatment of thromboembolism with intravenous heparin therapy in the early postoperative period following total joint arthroplasty.

BACKGROUND: Treatment of thromboembolism with intravenous heparin therapy in the early postoperative period after total joint arthroplasty has been associated with a high rate of complications. The purpose of the present study was to compare the rate of bleeding complications in a group of patients who required intravenous heparin therapy for the treatment of thromboembolism after total hip or knee arthroplasty with the rate in a control group of patients who received only prophylactic anticoagulation. METHODS: The postoperative courses of forty-four consecutive patients who were managed with intravenous administration of heparin and oral administration of warfarin for the treatment of a thromboembolic event following unilateral total hip or knee arthroplasty were compared with those of a control group of 376 consecutive patients who had these same procedures but did not have a thromboembolic complication. The patients in the control group were managed with prophylactic anticoagulation with use of enoxaparin. Sixty-eight percent (thirty) of the forty-four patients in the heparin group received the initial dose of heparin on or before the fourth postoperative day, and 82 percent (thirty-six) received an initial bolus of 5000 units of heparin at the initiation of therapy. RESULTS: The rate of bleeding complications was 9 percent (four of forty-four) in the heparin group, compared with 6 percent (twenty-three of 376) in the control group (p = 0.44). The mean transfusion requirement in the heparin group (1.8 units of packed red blood cells) was significantly greater than that in the control group (0.8 unit) (p < 0.0001). Three of the four patients who had a bleeding complication while receiving heparin and warfarin had coagulation parameters that were substantially higher than recommended levels. The mean duration of hospitalization in the heparin group (fifteen days) was significantly longer than that in the control group (seven days) (p < 0.0001). CONCLUSIONS: The results of the present study suggest that the use of intravenous heparin therapy for the treatment of thromboembolism in the early postoperative period after total joint arthroplasty is associated with a rate of bleeding complications that is similar to that associated with the use of prophylactic anticoagulation with use of enoxaparin alone. One should expect an increased transfusion requirement and a longer duration of hospitalization for patients who require intravenous heparin therapy for the treatment of a thromboembolic event.

Treatment of de Quervain's disease:role of conservative management.

This retrospective study compares two methods used to treat de Quervain's disease: splintage with oral non-steroidal anti-inflammatory drugs (NSAIDs) and steroid injection. Patients were separated into three groups based on symptom severity: group I-minimal, group II-mild, and group III-moderate or severe. Three hundred and nineteen wrists in 300 patients were followed from one to six years. Fifteen of 17 patients with minimal symptoms were relieved with splintage and NSAIDs. However, only seven of 20 in Group II and two of eight in Group III treated similarly were relieved. Of the 249 patients in Group III treated with injections, 76% were completely relieved, 7% were improved, and 4% were not improved. We conclude that classification of patients' with de Quervain's disease based on their pre-treatment symptoms may assist surgeons in selecting the most efficacious treatment and in providing prognostic information to their patients.

Wrist anatomy.

The multiple joints within the wrist form a complex structure capable of transmitting significant loads to the upper extremity while providing a mobile base for the precision movements of the hand. This duality is accomplished through a fine interplay between the carpal bones and an arrangement of highly specific ligamentous structures, a system loaded by balanced muscle forces.

The effectiveness of cut-proof glove liners: cut and puncture resistance, dexterity, and sensibility.

Five types of commercial glove liners (within double latex gloves) were compared to single and double latex gloves for cut and puncture resistance and for relative manual dexterity and degree of sensibility. An apparatus was constructed to test glove-pseudofinger constructs in either a cutting or puncture mode. Cutting forces, cutting speed, and type of blade (serrated or scalpel blade) were varied and the time to cut-through measured by an electrical conductivity circuit. Penetration forces were similarly determined with a scalpel blade and a suture needle using a spring scale loading apparatus. Dexterity was measured with an object placement task among a group of orthopedic surgeons. Sensibility was assessed with Semmes-Weinstein monofilaments, two-point discrimination, and vibrametry using standard techniques and rating scales. A subjective evaluation was performed at the end of testing. Time to cut-through for the liners ranged from 2 to 30 seconds for a rapid oscillating scalpel and 4 to 40 seconds for a rapid oscillating serrated knife under minimal loads. When a 1 kg load was added, times to cut-through ranged from 0.4 to 1.0 second. In most cases, the liners were superior to double latex. On average, 100% more force was required to penetrate the liners with a scalpel and 50% more force was required to penetrate the liners with a suture needle compared to double latex. Object placement task times were not significantly liners compared to double latex gloves. Semmes-Weinstein monofilaments, two-point discrimination, and vibrametry showed no difference in sensibility among the various liners and double latex gloves. Subjects felt that the liners were minimally to moderately impairing. An acclimation period may be required for their effective use.

Technique for removal of femoral components with intercondylar articulation in total knee arthroplasty.

Total knee revision arthroplasty is a challenging and demanding procedure. Removal of well-fixed implants must be done meticulously to preserve bone stock. The presence of intercondylar geometries compounds this problem because the cement-metal interface is inaccessible. The authors present a new technique for approaching this region using a high speed metal cutting burr, thus effectively preserving bone stock in the distal femur.

Allografting in total knee replacement arthroplasty.

Revision, and complicated primary total knee arthroplasty (TKA), may present with significant structural bony defects. Allograft offers blocks of material that can be shaped to the defect. The opportunity to gain a biological bond may theoretically enhance loading conditions and enhance any subsequent surgery. However, the biomechanical and biological issues of immune response, infection, graft incorporation, resorption, and load transfer render allografting a powerful but problematic technology.

Femoral shaft fracture in porous and press-fit total hip arthroplasty.

Press-fit and porous femoral components for total hip replacements are currently designed for aggressive canal filling. The bulk of the implants and their manner of insertion have created new femoral fracture problems in hip arthroplasty. Sixteen femoral fractures occurred in a series of 79 press-fit or porous arthroplasties in 72 patients. All cases in this report were reviewed through the period of fracture healing. The fractures were classified as follows: type I, at the neck medially, or proximal to the isthmus laterally; type II, running in a spiral oblique pattern from the stem tip; type III, originating in stress risers in the femoral shaft; and type IV, miscellaneous unclassifiable fractures. All fractures healed, leaving painless hips (Harris hip score average, 84). Collared implants are recommended in proximal fractures to protect against acute subsidence due to a wedging mechanism.

Early experience with the Autophor prosthesis using a posterior approach.

Twenty-eight Autophor hip prostheses have been implanted in 25 patients, using primarily a posterior approach. Complications have included two dislocations and two femoral shaft fractures. One dislocation required reoperation. The shaft fractures healed in three months with bone grafting and cerclage wiring. There were no infections and no cases of loosening or component failure. Radiological follow-up including bone scan suggests implant boney stabilization at six months. Our early experience suggests that this implant is quite successful, especially in the young patient and the patient with significant loss of bone stock from protrusio or revision surgery.

Unusual fragment displacement in a distal radius fracture.

A 25-year-old man sustained a closed comminuted intra-articular fracture of the distal radius. Tomography showed 180 degree rotation of a palmar medial articular fragment. This rare injury is mentioned only once in the literature. When recognized, open reduction and internal fixation are necessary.

Stiffness of small-bone external fixation methods: an experimental study.

A variety of small-bone external fixation methods were evaluated to determine bending and torsional stiffness. Several methods of external pin stabilization with bone cement and with a commercial device were used. Among experimental variables examined were: the number of pins, pin diameter, pin length, pin spacing, and pin threading. The most rigid fixation was achieved with four pins held with a wire-reinforced bone cement fixator. Pin diameter was the most significant variable in the determination of stiffness with this configuration.

Synovectomy, radial head excision, and anterior capsular release in stage III inflammatory arthritis of the elbow.

A retrospective study was performed to analyze the results of elbow synovectomy, radial head excision, and anterior capsular release in 12 elbows in 11 patients with radiographic stage III inflammatory arthritis. The follow-up period averaged 6.1 years. Average flexion arc improved from 93 degrees (range, 80 degrees-110 degrees) to 116 degrees (range, 65 degrees-140 degrees), with flexion contracture improving 13 degrees. Total arc of forearm rotation increased from 95 degrees to 145 degrees. Ewald scores improved from an average of 37 to 84 points. Pain was eliminated or improved in all cases; functional improvement was noted in all patients. Serial postoperative radiographs showed no significant disease progression over time. These results suggest that combined synovectomy, radial head excision, and anterior capsular release effectively relieves pain and improves function in stage III inflammatory arthritis of the elbow.

Results of total knee replacement using an uncemented tibial component.

Fourteen patients (16 knees) underwent total knee arthroplasty with a noncemented tibial component. Clinical evaluation at one year and two years showed a level of function and pain relief comparable to that reported in studies of cemented prostheses. Radiographic studies demonstrated evidence of active bone implant consolidation.

Technical note: a modified Harris trochanteric reattachment technique.

A trochanteric reattachment technique which does not penetrate the femoral canal with wire has been developed for use in revision surgery or with press-fit implants. This technique was shown by in vitro mechanical testing to be comparable in stability to the standard Harris trochanteric reattachment method. It has been used successfully in 15 clinical cases.

Stability of press-fit acetabular cups.

Mechanical tests were performed to characterize the initial stability of press-fit cups as a function of cup design, surface structure, and surgical preparation. Eight cups from six manufacturers were press-fit into acetabular cavities prepared in two densities of Sawbones polyethylene foam and in bovine knee trabecular bone. Cavity sizes and cup loading forces were varied. Acetabular defects were simulated in the Sawbones model. Preparations were tested to determine axial-rotatory and tangential ("levering-out") stability. Results suggested that cup geometry and proper surgical technique--in particular, proper sizing and depth of the acetabular cavity--are important in determining initial cup stability independent of adjuvant screw or spike fixation. Stability is a function of the area of interface contact between the cup rim and the substrate. If the cavity is too small or too shallow, and the substrate too dense, the cup will not seat to the rim and stability will be compromised. If there are defects in the rim, the area of interface contact will be diminished and stability compromised. Cups with a true hemispherical design have a greater area of rim interface contact than "low-profile" cups and are therefore more stable. 1 mm undersizing of the cavity (or 2 mm undersizing in less dense substrate) appears to provide optimal stability.

A novel technique for the removal of well-fixed, porous-coated acetabular components with spike fixation.

The removal of well-fixed, porous-coated acetabular components at the time of revision total hip arthroplasty can be challenging. The presence of spike fixation can increase the difficulty of removing an acetabular component because traditional methods of component removal, such as the use of curved gouges, may not be possible. We report a novel technique for the removal of well-fixed, porous-coated acetabular components with adjunctive spike fixation. This technique uses an overlay template that targets the spikes for removal with a high-speed, carbide-tipped bur.

Cementless total knee arthroplasty in patients with inflammatory arthritis and compromised bone.

Patients with bone compromised by inflammatory arthritis and medications are often excluded from cementless total knee arthroplasty (TKA) because of concerns regarding implant fixation and ingrowth. However, many such patients are young and at long-term risk for implant failure no matter what the fixation technique. Improved implant designs and technique may improve results. Cementless arthroplasty was performed in 45 patients with inflammatory arthritis. There were 38 patients with 53 implants available for follow-up evaluation during a 2- to 6.4-year period (average, 3.3 years). Medications included steroids (16 patients), nonsteroidal antiinflammatory drugs (36 patients), and cytotoxic agents (12 patients). Twenty-nine patients were using at least two types of medication. Prostheses included the Tricon P, Tricon M, Miller-Galante, and Anatomic Modular Knee (AMK) prosthesis. The procedures were performed using standard ligament-balancing techniques. Tibial resections were within 1 cm of the tibial plateau, thereby necessitating extensive bone grafts in ten patients. Tibial components were chosen for maximal cortical rim contact. Roentgenograms were reviewed for alignment, tibial rim contact, radiolucencies, gaps, sclerosis, and subsidence. Patients with no evidence of gap or lucency had spot films under image control. Hospital for Special Surgery knee scores averaged 47 preoperatively and 88 at follow-up examination. Alignment was from 3 degrees valgus to 9 degrees valgus (average, 6 degrees valgus), with a tibial axis of 0 degrees +/- 2 degrees. Plateau coverage was within 2.4 mm (average) of the cortical rim in all planes in the anteroposterior (AP) and lateral views. Tibial sclerosis occurred with equal frequency in all AP zones and was present equally in anterior and posterolateral zones. Gaps and lucencies were more common laterally. Fifteen femoral components showed a disturbing, localized osteopenia. Sclerosis, gap, and lucency were most common anteriorly. Cementless TKA with appropriate technique can produce results comparable to cemented surgery in patients with bone quality compromised by inflammatory arthritis, steroids, and nonsteroidal and cytotoxic agents. The femoral bone response suggests an intimate bone implant relationship. The tibia shows little direct coupling of prosthesis to bone. These responses are similar to reports from other studies. Fixation is sufficient to allow for continued analysis over time and results are encouraging.