Effects of cyclooxygenase and soluble epoxide hydrolase inhibitors on apoptosis of cultured primary equine chondrocytes.

BACKGROUND: Apoptosis is an important mechanism underlying chondrocyte loss in osteoarthritis that could be affected by modulation of lipid signaling via inhibition of cyclooxygenases (COX) and soluble epoxide hydrolase (sEH). OBJECTIVE: To determine the impact of inhibiting COX and sEH alone or in combination on apoptosis of equine chondrocytes. METHODS: Cultured primary equine chondrocytes were subjected to serum deprivation or incubation with 1 µg/ml tunicamycin for 24 h to induce apoptosis via caspase activation and endoplasmic reticulum (ER) stress, respectively. Cells were treated with the non-selective COX inhibitor phenylbutazone, the COX-2 selective inhibitor firocoxib and the sEH inhibitor t-TUCB alone or in combination. The inhibitors were used at half-maximal (IC50), 80% of maximal (IC80) and 10-fold the 80% inhibitory concentration (10xIC80) for the equine enzymes. Apoptosis was quantified via ELISA technique. Data were analyzed with unpaired two-tailed t-test or one-way ANOVA followed by Bonferroni's post-hoc while correcting for multiple comparisons via statistical hypothesis testing. P < 0.05 was considered significant. RESULTS: In the caspase model, 10xIC80t-TUCB significantly decreased whereas 10xIC80 phenylbutazone significantly enhanced apoptosis. Apoptosis enhancement by phenylbutazone was significantly attenuated by concurrent 10xIC80t-TUCB. The remaining treatments and concentrations had no effect on apoptosis development. In the ER stress model, IC50 and IC80 phenylbutazone and firocoxib significantly enhanced apoptosis, which was fully prevented by concurrent 10xIC80t-TUCB. MAIN LIMITATIONS: In vitro findings that will need to be verified in vivo. CONCLUSIONS: Chondrocyte apoptosis caused by ER stress can be enhanced by COX inhibition but prevented by concurrent inhibition of sEH.

The association between collagen and bone biomarkers and radiographic osteoarthritis in the distal tarsal joints of horses.

BACKGROUND: Osteoarthritis (OA) of the distal intertarsal (DIT) and tarsometatarsal (TMT) joints occurs commonly. Synovial fluid (SF) biomarkers of collagen and bone turnover have potential clinical value. OBJECTIVES: To measure SF biomarker concentrations from DIT and TMT joints in adult horses and determine if they correlate with radiographic OA severity and are higher in joints with radiographic OA compared to controls. STUDY DESIGN: Cross-sectional. METHODS: Radiographic OA of DIT and TMT joints was evaluated from adult horses (5-35 years old). Overall radiographic scores divided horses into those with mild or moderate radiographic OA (16 joints from 9 horses) or controls (13 joints from 9 horses). Direct biomarkers of OA (Carboxypropeptide of type II collagen = CPII, carboxy-neoepitope of type II collagen exposed after collagenase-cleavage = C2C, Bone alkaline phosphatase = BAP and Chondroitin sulfate epitope = CS846) were measured via ELISA and CPII/C2C was calculated. Biomarkers were correlated with radiographic findings and concentrations from those with radiographic OA to control joints and were compared. RESULTS: Concentrations of CPII (R = 0.84, P<0.001), C2C (R = 0.69, P<0.001) and BAP (R = 0.41, P = 0.03) as well as CPII/C2C (R = 0.69, P<0.001) values positively correlated with overall radiographic scores. Adjusted means ± s.d., after controlling for age, for CPII (P<0.001), C2C (P<0.001), CPII/C2C (P = 0.004) and BAP (P = 0.05) were significantly higher in DIT and TMT joints with radiographic OA (CPII: 2174.45 ± 1064.01; C2C: 233.52 ± 51.187; CPII/C2C: 9.01 ± 4.09; BAP: 21.98 ± 15.34) compared to controls (CPII: 594.53 ± 463.05; C2C: 153.12 ± 48.95; CPII/C2C: 3.96 ± 2.38; BAP: 12.76 ± 3.61). CPII (P<0.001), C2C (P = 0.001) and CPII/C2C (P = 0.001) were significantly higher with moderate radiographic OA (CPII: 2444.61 ± 772.78; C2C: 248.90 ± 44.94; CPII/C2C: 9.47 ± 2.97) compared to controls (CPII: 658.38 ± 417.36; C2C: 156.49 ± 47.61; CPII/C2C: 4.15 ± 2.04), with CPII also showing significantly higher concentrations (P = 0.04) with mild radiographic OA compared (1515.00 ± 584.95) to controls (658.38 ± 417.36). There were no differences in CS846 concentrations between radiographic OA and control joints. Age positively correlated with CPII (R = 0.48, P = 0.01) and C2C (R = 0.44, P = 0.02) concentrations. MAIN LIMITATIONS: Radiographic OA was assessed, not clinical lameness. Controls were not age-matched to those with spontaneous radiographic OA. CONCLUSIONS: There is an association between collagen (CPII, C2C and CPII/C2C) and bone (BAP) biomarkers and radiographic OA in the distal tarsal joints of horses.

Circumferential hoof clamp method of lameness induction in the horse.

A circumferential hoof clamp method to induce controlled and reversible lameness in the forelimbs of eight horses was assessed. Peak vertical forces and vertical impulses were recorded using a force plate to verify induced lameness. Video recordings were used by blinded observers to determine subjective lameness using a 0-5 scale and any residual lameness following clamp loosening. Tightening of clamps resulted in consistent, visible lameness in the selected limbs in all horses. Lameness was confirmed by significant decreases from baseline in the peak vertical force (P <0.01). Lameness was also confirmed subjectively by elevated median scores (0 at baseline and 2 during lameness). Lameness was not immediately reversible after clamp loosening (median score 1.5), but horses were not obviously lame after clamp removal and were no different from initial baseline (median score 0.5) approximately 3 days later.

Posture and movement characteristics of forward and backward walking in horses with shivering and acquired bilateral stringhalt.

REASONS FOR PERFORMING STUDY: To investigate and further characterise posture and movement characteristics during forward and backward walking in horses with shivering and acquired, bilateral stringhalt. OBJECTIVES: To characterise the movement of horses with shivering (also known as shivers) in comparison with control horses and horses with acquired bilateral stringhalt. STUDY DESIGN: Qualitative video analysis of gait in horses. METHODS: Owners' and authors' videos of horses with shivering or stringhalt and control horses walking forwards and backwards and manually lifting their limbs were examined subjectively to characterise hyperflexion, hyperextension and postural abnormalities of the hindlimbs. The pattern and timing of vertical displacement of a hindlimb over one stride unit was evaluated among control, shivering and stringhalt cases. RESULTS: Gait patterns of shivering cases were characterised as follows: shivering-hyperextension (-HE, n = 13), in which horses subjectively showed hyperextension when backing and lifting the limb; shivering-hyperflexion (-HF, n = 27), in which horses showed hindlimb hyperflexion and abduction during backward walking; and shivering-forward hyperflexion (-FHF, n = 4), which resembled shivering-HF but included intermittent hyperflexion and abduction with forward walking. Horses with shivering-HF, shivering-FHF and stringhalt (n = 7) had a prolonged swing phase duration compared with control horses and horses with shivering-HE during backward walking. With the swing phase of forward walking, horses with stringhalt had a rapid ascent to adducted hyperflexion of the hindlimb, compared with a rapid descent of the hindlimb after abducted hyperflexion in horses with shivering-FHF. CONCLUSIONS: Shivering affects backward walking, with either HE or HF of hindlimbs, and can gradually progress to involve intermittent abducted hyperflexion during forward walking. Shivering-HF and shivering-FHF can look remarkably similar to acquired bilateral stringhalt during backward walking; however, stringhalt can be distinguished from shivering-HF by hyperflexion during forward walking and from shivering-FHF by an acute onset of a more consistent, rapidly ascending, hyperflexed, adducted hindlimb gait at a walk.

Vascular perfusion of the dorsal and palmar condyles of the equine third metacarpal bone.

REASONS FOR PERFORMING STUDY: Palmar osteochondral disease (POD) is an overload arthrosis that commonly affects fetlock joints of racing Thoroughbreds (TB) but the aetiopathogenesis of the disease has not been well defined. OBJECTIVES: The aim of this study was to compare India ink perfusion in the dorsal and palmar condyles of the third metacarpal bone (McIII) in both passively flexed and maximally extended fetlock joints from paired equine cadaver limbs. STUDY DESIGN: Descriptive cadaver study comparing perfusion of condyles of McIII in paired cadaver limbs in flexion (control group) and maximal extension (intervention group). METHODS: Pairs of forelimbs were acquired from 5 TB horses subjected to euthanasia for reasons unrelated to lameness. Limb pairs were perfused intra-arterially with India ink and then randomly assigned to passive flexion or maximal extension of the fetlock joint. Limbs were sectioned sagittally in 3 mm sections through the fetlock and 12 sections per limb processed using a modified tissue-clearing technique. Sections were subsequently digitally imaged and bone perfusion evaluated with image analysis software. RESULTS: Greater perfusion of the dorsal condyle than of palmar condyle was observed in 78% of sections from limbs in passive flexion and 92% of maximally extended sections. Perfusion to the palmar aspect of the condyle was significantly decreased (P < 0.0001) when the limbs were placed in maximal extension compared to passive flexion. CONCLUSIONS: The palmar condyle of McIII had less perfusion than the dorsal condyle when the fetlock joint was in passive flexion and this difference was exacerbated by maximal extension. Based on the anatomical location of POD lesions, perfusion differences between the dorsal and palmar condyles of McIII may be associated with development of these lesions.

Non-terminal animal model of post-traumatic osteoarthritis induced by acute joint injury.

OBJECTIVE: Develop a non-terminal animal model of acute joint injury that demonstrates clinical and morphological evidence of early post-traumatic osteoarthritis (PTOA). METHODS: An osteochondral (OC) fragment was created arthroscopically in one metacarpophalangeal (MCP) joint of 11 horses and the contralateral joint was sham operated. Eleven additional horses served as unoperated controls. Every 2 weeks, force plate analysis, flexion response, joint circumference, and synovial effusion scores were recorded. At weeks 0 and 16, radiographs (all horses) and arthroscopic videos (OC injured and sham joints) were graded. At week 16, synovium and cartilage biopsies were taken arthroscopically from OC injured and sham joints for histologic evaluation and the OC fragment was removed. RESULTS: OC fragments were successfully created and horses were free of clinical lameness after fragment removal. Forelimb gait asymmetry was observed at week 2 (P = 0.0012), while joint circumference (P < 0.0001) and effusion scores (P < 0.0001) were increased in injured limbs compared to baseline from weeks 2 to 16. Positive flexion response of injured limbs was noted at multiple time points. Capsular enthesophytes were seen radiographically in injured limbs. Articular cartilage damage was demonstrated arthroscopically as mild wear-lines and histologically as superficial zone chondrocyte death accompanied by mild proliferation. Synovial hyperemia and fibrosis were present at the site of OC injury. CONCLUSION: Acute OC injury to the MCP joint resulted in clinical, imaging, and histologic changes in cartilage and synovium characteristic of early PTOA. This model will be useful for defining biomarkers of early osteoarthritis and for monitoring response to therapy and surgery.

Steroid diffusion into the navicular bursa occurs in horses affected by palmar foot pain.

Palmar foot pain is frequently treated by steroid injections into the distal interphalangeal joint (DIPJ) in the anticipation that the steroid will diffuse to the navicular bursa and palmar foot structures. The object of this study was to determine if triamcinolone acetonide (TA) would in fact be able to locally diffuse from the DIPJ into the navicular bursa in horses affected by palmar foot pain. Both forelimb DIPJs (nine horses) were injected with 10 mg of TA. Navicular bursa fluid samples, both forelimb and one hind limb (systemic control), were analysed for TA with high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) six hours later. Foot radiographs were graded (0-4) on severity of changes. Forelimb navicular bursa TA concentrations (mean±sd log(10), 3.20±0.56) were significantly higher than systemic control concentrations (mean±sd log(10), 1.89±0.3) (P<0.0001). Horses with a radiographic grade of >2 were four times as likely to have TA log(10) concentrations less than 3.2 (158.49 ng/ml). TA locally diffused from the DIPJ into the navicular bursa in horses affected by palmar foot pain; TA concentrations decreased as radiographic severity increased.

Urinary CTX-II concentrations are elevated and associated with knee pain and function in subjects with ACL reconstruction.

OBJECTIVE: Post-traumatic knee osteoarthritis (OA) is prevalent after anterior cruciate ligament reconstruction (ACLR). Biomarkers that identify individuals likely to develop OA, especially symptomatic OA, can help target preventative and therapeutic strategies. This study examined the magnitude and change over time in urinary CTX-II (uCTX-II) concentrations shortly after ACL reconstruction, and, secondarily, the associations with knee pain and function. DESIGN: Subjects were 28 patients with ACLR and 28 age- and sex-matched controls (CNTRL). Testing was conducted at four time points spaced 4 weeks apart (4, 8, 12 and 16 weeks post-operative in ACLR). Measures included demographics, urine samples, Numeric Pain Rating Scale (NPRS) and International Knee Documentation Committee Subjective Knee Form (IKDC-SKF). uCTX-II concentrations were determined with competitive enzyme-linked immunosorbent assay (ELISA). uCTX-II concentrations at each time point in ACLR were compared to the mean concentration over time in CNTRL, with and without adjustment for body mass index (BMI). Changes over time in each measure and correlations between the slopes of change were examined. RESULTS: uCTX-II concentrations were significantly higher in ACLR than CNTRL through 16 weeks post-operative when adjusted for BMI. In ACLR, uCTX-II concentrations significantly decreased over time, and the slope was associated with NPRS (r = 0.406, P = 0.039) and IKDC-SKF (r = -0.402, P = 0.034) slopes. CONCLUSION: uCTX-II concentrations shortly after ACLR were elevated compared to CNTRL and declined over time. Decreasing uCTX-II concentrations were associated with decreasing knee pain and improving function. uCTX-II may have a role as a prognostic marker following ACLR and warrants further investigation.

Osteochondral injury increases type II collagen degradation products (C2C) in synovial fluid of Thoroughbred racehorses.

OBJECTIVES: To investigate the effects of exercise and osteochondral (OC) injury on type II collagen degradation products (collagenase cleavage neoepitope commercially known as C2C) in synovial fluid (SF) from Thoroughbred (TB) racehorses and to compare these results with radiographic and arthroscopic scores of severity of joint injury. METHODS: Metacarpophalangeal/metatarsophalangeal (MCP/MTP) and carpal SF was obtained from (1) 20 normal rested horses, (2) the same horses after 5 to 6 months of race training, and (3) 27 horses with OC injury from racing. For group 3, radiographic and arthroscopic scores were determined. Concentrations of SF C2C were determined by ELISA. RESULTS: SF C2C concentrations in OC injured carpal and MCP/MTP joints were significantly different than rested and exercised joints (P<0.01). However, carpal and MCP/MTP SF C2C concentrations were not significantly different between rested and exercised groups. Arthroscopic scores were significantly higher for OC injured carpal than OC injured MCP/MTP joints (P=0.002). OC injured SF C2C concentrations were positively correlated with radiographic and arthroscopic scores. Arthroscopic scores were positively correlated with radiographic scores. SF C2C concentrations >or= 64 pmol/mL for MCP/MTP joints and >or= 75 pmol/mL for carpal joints discriminated OC injured joints from rested or exercised joints. CONCLUSION: OC injury caused a significant increase in SF C2C concentrations in carpal and MCP/MTP joints compared to rested and exercised horses. SF C2C concentrations were correlated to severity of joint injury. Based on these findings, SF C2C analysis may be useful for evaluation of joint injury.

Volar plating of AO C3 distal radius fractures: biomechanical evaluation of locking screw and locking smooth peg configurations.

PURPOSE: The goal of this study was to determine whether locking screws or smooth locking pegs optimize fixation of AO C3 intra-articular distal radius fractures. A secondary goal was to determine which combinations of locking screws and smooth locking pegs influence construct stability. METHODS: In anatomic radius models, AO C3 intra-articular distal radius fractures were fixed using volar locking plates. For the first part, 16 specimens were randomized to receive either 2 locking screws or 2 smooth locking pegs in each of the 3 pairs of holes in the plate. For the second part, 30 specimens were randomized to receive any 4 combinations of locking screws and smooth locking pegs in each of the 3 pairs of holes. Axial loading to failure was applied. RESULTS: Constructs consisting of 4 smooth locking pegs within the lunate fragment were significantly weaker than constructs with 4 locking screws (means 626 N vs 981 N, respectively). Constructs with smooth locking pegs in the ulnar positions of the lunate fragment were weaker than with locking screws in these positions (means 737 N vs 977 N, respectively). Locking screws in the subchondral position of the lunate fragment were stronger than smooth locking pegs in these positions (means 1,227 N vs 934 N, respectively) and any other combination (means 1,227 N vs 942 N, respectively). CONCLUSIONS: Use of locking screws as opposed to smooth locking pegs for AO C3 intra-articular distal radius fractures, particularly subchondral and in the ulnar side of the lunate fragment, optimizes construct stability. This may have implications on postoperative rehabilitation protocols and may limit costs related to use of volar locking plates.

Joint dependent concentrations of bone alkaline phosphatase in serum and synovial fluids of horses with osteochondral injury: an analytical and clinical validation.

OBJECTIVES: Validate use of a commercially available immunoassay for measurement of bone alkaline phosphatase (BAP) in equine serum and synovial fluid (SF), and investigate the effects of osteochondral (OC) injury in horses on BAP concentrations in serum and SF. METHODS: SF was collected from 37 joints of 34 Thoroughbred (TB) racehorses undergoing arthroscopic surgery for the removal of OC fragments from either the carpal joints (n=18) or the metacarpo-/metatarsophalangeal (MP) joints (n=19). SF was also obtained from 52 joints of 16 normal TB horses, collected bilaterally from carpal joints of 10 horses (n=40), and MP joints of six horses (n=12). Blood was obtained from all 50 horses. A commercially available immunoassay was validated and subsequently used to determine equine serum and SF BAP concentrations. Correlations to radiographic and arthroscopic scores were assessed. RESULTS: BAP concentrations were significantly lower in serum from horses with OC injury in their carpal or MP joints than in serum from normal horses. SF BAP concentrations in normal and OC injured carpal joints were significantly higher than MP joints. BAP concentrations were significantly higher in SF from OC injured carpal joints than normal. BAP concentrations were affected by joint sampled, with age having a significant interaction. Concentrations of BAP in the serum (<30U/L), SF (>22U/L) and a ratio of SF to serum > or = 0.5 were predictive of OC injury. Radiographic and arthroscopic scores significantly correlated with serum BAP concentrations, and SF:serum BAP correlated with arthroscopic scores. CONCLUSIONS: Determination of serum and SF BAP concentrations may be beneficial in the investigation of early joint injury. Joint and injury dependent differences in BAP concentrations allowed the estimation of predictive value for identifying OC injury.

A simplified method of determining synovial fluid chondroitin sulfate chain length.

OBJECTIVE: To determine whether dimethylmethylene blue (DMMB) analysis, when combined with agarose gel filtration chromatography (Superose 6), can be performed instead of fluorophore-assisted carbohydrate electrophoresis (FACE) to determine chondroitin sulfate (CS) chain length in synovial fluid (SF). METHODS: SF was obtained from (1) normal horses after 8 weeks of rest, (2) the same horses after 9 months of treadmill training, and (3) horses with osteochondral (OC) injury from racing. SF CS concentrations and chain lengths were determined by gel chromatography and DMMB analysis and compared with previous results determined by FACE analysis on the same samples. RESULTS: DMMB analysis showed that SF CS peak chain length in the OC injury group increased significantly (18.7 kDa) when compared to rested and exercised normal horses (15.6 kDa). The assay had a positive predictive value of 71% and a negative predictive value of 75% for discriminating between normal and injured joints. CONCLUSIONS: We report a simple and inexpensive DMMB analysis of SF CS chain length, which, when coupled with Superose 6 chromatography, discriminates between normal and post-injury joints. Similar to our previous FACE analysis results [Brown MP, Trumble TN, Plaas AHK, Sandy JD, Romano M, Hernandez J, et-al. Exercise and injury increase chondroitin sulfate chain length and decrease hyaluronan chain length in synovial fluid. Osteoarthritis Cartilage 2007;15], our DMMB results show an increase in the chain length of the CS in the SF of injured joints.

Exercise and injury increase chondroitin sulfate chain length and decrease hyaluronan chain length in synovial fluid.

OBJECTIVES: (1) To investigate the effects of exercise and osteochondral (OC) injury on synovial fluid (SF) chondroitin sulfate (CS) and hyaluronan (HA) concentration and chain length, (2) to compare SF and cartilage CS data from joints with OC fragmentation, and (3) to compare SF CS and HA profiles with those seen in serum from the same horses. METHODS: Serum and SF were obtained from (1) normal horses after 8 weeks rest, (2) the same horses after 9 months treadmill training, and (3) horses with OC injury from racing. Articular cartilage was also collected from group 3 horses. Concentrations and chain lengths of CS and HA were determined by gel chromatography and fluorophore-assisted carbohydrate electrophoresis. RESULTS: SF CS peak chain length in the OC injury group increased significantly (18.7kDa) when compared to rested horses (11.6kDa), with exercise producing an intermediate chain length (15.6kDa). Cartilage and serum from the OC injury group had the abnormally long CS chains seen in SF from these horses. Total SF HA was significantly lower in the OC injury group compared to the rested group. Both the OC injury group and the exercised group had significant decreases in SF HA chain length compared to the rested group. CONCLUSIONS: Chain length of SF CS was increased by exercise and OC injury. Exercise resulted in a modest increase, whereas OC injury caused a marked increase. In contrast to CS, SF HA chain length was decreased by OC injury, and to a lesser extent by exercise. Chain length analysis of SF CS and HA may provide a useful tool for evaluation of joint health.

Indirect reduction and percutaneous fixation versus open reduction and internal fixation for displaced intra-articular fractures of the distal radius: a randomised, controlled trial.

A total of 179 adult patients with displaced intra-articular fractures of the distal radius was randomised to receive indirect percutaneous reduction and external fixation (n = 88) or open reduction and internal fixation (n = 91). Patients were followed up for two years. During the first year the upper limb musculoskeletal function assessment score, the SF-36 bodily pain sub-scale score, the overall Jebsen score, pinch strength and grip strength improved significantly in all patients. There was no statistically significant difference in the radiological restoration of anatomical features or the range of movement between the groups. During the period of two years, patients who underwent indirect reduction and percutaneous fixation had a more rapid return of function and a better functional outcome than those who underwent open reduction and internal fixation, provided that the intra-articular step and gap deformity were minimised.

Synovial fluid gelatinase concentrations and matrix metalloproteinase and cytokine expression in naturally occurring joint disease in horses.

OBJECTIVES: To determine concentrations of matrix metalloproteinase (MMP)-2 and -9 in synovial fluid; and mRNA expression of MMP-1, -13, and -3; interleukin[IL]-1alpha and beta; and tumor necrosis factor (TNF)-alpha in synovial membrane and articular cartilage from horses with naturally occurring joint disease. SAMPLE POPULATION: Synovial fluid (n = 76), synovial membrane (59), and articular cartilage (45) from 5 clinically normal horses and 55 horses with joint disease categorized as traumatic (acute [AT] or chronic [CT]), osteochondritis dissecans (OCD), or septic (S). PROCEDURE: Synovial fluid gelatinase concentrations were analyzed, using zymography. Synovial membrane and articular cartilage mRNA expression for MMP-1, -3, and -13, IL-1alpha and beta, TNF-alpha, type-II collagen, and aggrecan were analyzed, using quantitative reverse transcriptase-polymerase chain reaction. RESULTS: Synovial fluid pro-MMP-2 concentration was significantly higher in diseased joints than normal joints. Septic joints had significantly higher concentrations of pro and active MMP-9. Stromelysin-1 was expressed in > or = 80% of synovial membrane and articular cartilage samples and was strongly influenced by age. Collagenases were rarely expressed, with MMP-13 expressed only in diseased joints. Interleukin-1beta expression was significantly higher in all OCD samples and was influenced by age. Tumor necrosis factor-alpha expression was significantly higher in cartilage from joints with AT and OCD. There was no correlation between MMP or cytokines and type-II collagen or aggrecan expression. CONCLUSIONS AND CLINICAL RELEVANCE: Matrix metalloproteinase-2 and -3 are abundant in naturally occurring joint disease and normal joints. Interleukin-1beta and TNF-alpha may be important in the pathogenesis of OCD. Age affects MMP and IL-1beta concentrations.

Endoscopic versus open surgical treatment of carpal tunnel syndrome.

The impact of CTS is significant as evidenced by the fact that only back injuries result in greater rates of employee absenteeism in the workplace. CTR is now the most commonly performed surgical procedure in the United States. Earlier efforts using open surgical techniques were associated with significant morbidity, which some would argue is greater than that associated with the disease itself. The addition of endoscopy to surgeon's armamentarium offers the promise of decreased morbidity associated with the surgical treatment of CTS. Evidence indicates that when compared with open CTR, endoscopic CTR results in earlier achievement of patient satisfaction and functional outcomes. As a result, it is becoming clear that endoscopic surgery is a safe and effective method of treating CTS.

Disorders of the thumb sesamoids.

The subsesamoid joints of the thumb are a common site of arthritis, but their small size makes diagnosis of disorders challenging. The sesamoid and subsesamoid joints may also be injured acutely with the volar plate complex during hyperextension injuries, and may sometimes produce mechanical dysfunction. Simple excision of chronically painful sesamoids provides excellent relief.

A preliminary study of joint surface changes after an intraarticular fracture: a sheep model of a tibia fracture with weight bearing after internal fixation.

OBJECTIVE: To evaluate the changes in the articular cartilage and subchondral bone after an osteotomy designed to simulate an articular fracture. DESIGN: The contribution of the cartilage and subchondral bone was evaluated twelve weeks after creating a 1.0-millimeter step-off in the medial plateau of the tibia of twelve adult domestic sheep. All animals surviving were labeled with fluorescent markers for bone production, oxytetracycline (fifty milligrams per kilogram), and calcein (twelve milligrams per kilogram) nine and 11.5 weeks after surgery. The knees were loaded in compression using an Instron materials tester with pressure-sensitive film to record joint contact pressures above and below the medial meniscus. SETTING: The studies were performed in the research laboratories of the Orthopaedic Laboratory at Harborview Medical Center in Seattle, Washington and the Madigan Army Medical Center in Tacoma, Washington. ANIMALS: Twelve adult domestic sheep. INTERVENTION: An intraarticular osteotomy of the medial tibial plateau with 1.0 millimeter of displacement was performed. The osteotomy was stabilized with 3.5-millimeter lag screws. MAIN OUTCOME MEASURES: The contact pressures of the knee joint and articular histology were evaluated twelve weeks after surgery. Samples of the articular cartilage were analyzed by light microscopy and electron microscopy to evaluate the response of the articular cartilage and subchondral bone of the differential joint loading because of the irregularity in the articular surface caused by the osteotomy. RESULTS: The knees with an intraarticular step-off had two major contact areas with an intervening zone of reduced load corresponding to the edge of the depressed fragment. Coronal histologic sections through the articular surface showed the presence of thinning and fibrillation on the high side of the step-off and some compensatory hypertrophy of the cartilage. The subchondral bone was not responsible for restoring articular congruity because the rate of bone production was similar between the low side of the articular fracture (1.85 micrometers per day) and the high side of the fracture (1.67 micrometers per day). Scanning electron microscopy showed partial cartilage remodeling by deformation of the high side cartilage with bending of the vertical collagen fibrils, even in the unloaded state. CONCLUSIONS: In this model with a small fracture displacement (1.0 millimeter), which was less than the thickness of the articular cartilage (1.5 millimeters), the contour of the joint improved despite residual articular surface incongruency after the fracture healing.

Axonal regeneration stimulated by the combination of nerve growth factor and ciliary neurotrophic factor in an end-to-side model.

The aim of this study was to investigate the potential for stimulating axonal regeneration in the context of end-to-side coaptation using a combination of nerve growth factor and ciliary neurotrophic factor in the rat sciatic nerve model. Four experimental groups (n = 8) were used: end-to-side coaptation only, end-to-side coaptation plus growth factor injection, primary repair, and nontransferred gap control. Twenty weeks after surgery histologic analysis showed that the ratio of axon density was significantly increased for the growth factor injection group. Histologic evidence suggested contamination from the proximal peroneal stump. Electrical stimulation and muscle weights showed that the target muscles had been reinnervated in all groups except the nontransferred gap control group. These data support the conclusion that the use of nerve growth factor and ciliary neurotrophic factor in combination may enhance regeneration in the peripheral nervous system. This is consistent with previous reports on the central nervous system and suggests a potential application in future studies aimed at improving peripheral nerve regeneration. Another conclusion is that contamination from the proximal peroneal stump may explain the regeneration observed in the end-to-side model. Further study using retrograde labeling is needed to establish the origin of the regenerating axons. Finally, evidence suggests that regenerating axons can use the epineurium of an intact nerve to bridge a gap in continuity.

Arthroscopic repair of triangular fibrocartilage complex injuries.

The triangular fibrocartilage complex is a functionally and anatomically intricate group of structures located at the ulnar aspect of the wrist. Injury to this structure affects the biomechanics of the wrist and makes functional restoration difficult. This article reviews the anatomy, biomechanics, diagnosis, and arthroscopic treatment of triangular fibrocartilage complex injuries.