Different changes in the biomarker C-terminal telopeptides of type II collagen (CTX-II) following intra-articular injection of high molecular weight hyaluronic acid and oral non-steroidal anti-inflammatory drugs in patients with knee osteoarthritis: a multi-center randomized controlled study.

OBJECTIVES: We previously reported, based on a multicenter randomized-control study, that the efficacy of intra-articular injections of hyaluronic acid (IA-HA) was not inferior to that of oral non-steroidal anti-inflammatory drugs (NSAIDs) in patients with knee osteoarthritis (OA). However, the molecular effects on the pathophysiology of knee OA remain unclear. C-terminal telopeptides of type II collagen (CTX-II) is reported to primarily originate from the interface between articular cartilage and subchondral bone, which is a site of potential remodeling in OA. We performed a predefined sub-analysis of the previous study to compare the changes of urinary CTX-II (uCTX-II) in response to IA-HA to those in response to NSAID for knee OA. DESIGN: A total of 200 knee OA patients were registered from 20 hospitals and randomized to receive IA-HA (2,700 kDa HA, 5 times at 1-week intervals) or NSAID (loxoprofen sodium, 180 mg/day) for 5 weeks. The uCTX-II levels were measured before and after treatment. RESULTS: The uCTX-II levels were significantly increased by IA-HA treatment (337.7 ± 193.8 to 370.7 ± 234.8 ng/µmol Cr) and were significantly reduced by NSAID treatment (423.2 ± 257.6 to 370.3 ± 250.9 ng/µmol Cr). The %changes of uCTX-II induced by IA-HA (11.6 ± 29.5%) and NSAID (-9.0 ± 26.7%) was significantly different (between-group difference: 20.6, 95% confidence intervals: 10.6 to 30.6). CONCLUSIONS: While both IA-HA and NSAID improved symptoms of knee OA, uCTX-II levels were increased by IA-HA and reduced by NSAIDs treatment, suggesting these treatments may improve symptoms of knee OA through different modes of action.

A longitudinal study of the quantitative evaluation of patella cartilage after total knee replacement by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping at 3.0 T: preliminary results.

OBJECTIVE: To characterize the quantitative changes of patella cartilage over time after total knee arthroplasty (TKA) by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping at 3.0 T. METHOD: Twenty-six knees of 26 patients (23 women and three men, mean age, 75 years) with primary osteoarthritis and osteonecrosis of the knee underwent TKA with a zirconia ceramic implant in this prospective study. Twelve patients without patella resurfacing (NR group) and 14 patients with patella resurfacing (R group) had TKA with cemented fixation. The implant position was examined by radiograph, computed tomography (CT) and magnetic resonance imaging (MRI). The clinical scores were checked pre-operatively, 1 year post-operatively and at the final follow-up. Patella cartilage and its thickness were evaluated pre-operatively and 1 year after TKA by dGEMRIC and T2 mapping in the NR group only. Patella cartilage was divided into eight regions of interest: the deep and superficial layers of the outer lateral and medial half, and the inner lateral and medial half from the central ridge. RESULTS: The implant position was appropriate in all cases and clinical scores were not significantly different between the two groups. The post-operative dGEMRIC value of the outer medial half superficial zone in the NR group was significantly decreased compared with the pre-operation value (P<0.05), whereas T2 mapping was not significantly changed in all zones. The cartilage thickness of the outer zone was significantly thinner post-operatively (P<0.05). CONCLUSIONS: These findings indicate that osteoarthritic changes in the outer zone of patella cartilage occurred 1 year after TKA.

Atelocollagen-associated autologous chondrocyte implantation for the repair of chondral defects of the knee: a prospective multicenter clinical trial in Japan.

BACKGROUND: New tissue-engineering technology was developed to create a cartilage-like tissue in a three-dimensional culture using atelocollagen gel. The minimum 2-year followup outcome of transplanting autologous chondrocytes cultured in atelocollagen gel for the treatment of full-thickness defects of cartilage in knees was reported from the single institution. The present multicenter study was conducted to determine clinical and arthroscopic outcomes in patients who underwent atelocollagen-associated autologous chondrocyte implantation for the repair of chondral defects of the knees. METHODS: At six medical institutes in Japan, we prospectively evaluated the clinical and arthroscopic outcomes of transplanting autologous chondrocytes cultured in atelocollagen gel for the treatment of full-thickness defects of cartilage in 27 patients (27 knees) with cartilage lesions on a femoral condyle or on a patellar facet over 24 months. RESULTS: The Lysholm score significantly increased from 60.0 +/- 13.7 points to 89.8 +/- 9.5 points (P = 0.001). Concerning the ICRS grade for arthroscopic appearance, 6 knees (24%) were assessed as grade I (normal) and 17 knees (68%) as grade II (nearly normal). There were few adverse features, except for detachment of the graft in two cases. CONCLUSIONS: We concluded that transplanting chondrocytes in a newly formed matrix of atelocollagen gel can promote restoration of the articular cartilage of the knee.

Decrease in anterior knee laxity by electrical stimulation of normal and reconstructed anterior cruciate ligaments.

We have investigated the changes in anterior laxity of the knee in response to direct electrical stimulation of eight normal and 45 reconstructed anterior cruciate ligaments (ACLs). In the latter, the mean time from reconstruction was 26.7 months (24 to 32). The ACL was stimulated electrically using a bipolar electrode probe during arthroscopy. Anterior laxity was examined with the knee flexed at 20 degrees under a force of 134 N applied anteriorly to the tibia using the KT-2000 knee arthrometer before, during and after electrical stimulation. Anterior tibial translation in eight normal and 17 ACL-reconstructed knees was significantly decreased during stimulation, compared with that before stimulation. In 28 knees with reconstruction of the ACL, in 22 of which the grafts were found to have detectable somatosensory evoked potentials during stimulation, anterior tibial translation was not decreased. These findings suggest that the ACL-hamstring reflex arc in normal knees may contribute to the functional stability and that this may not be fully restored after some reconstructions of the ACL.

Sensory neurons regenerate more dominantly than motoneurons during the initial stage of the regenerating process after peripheral axotomy.

This study was designed to determine whether sensory neurons or motoneurons were dominant during the earlier stage of the regeneration process after peripheral axotomy. After transection of the right sciatic nerves of rats, epineurial end neurorrhaphy was performed. At 5, 7 and 14 days postoperatively, the nerves were re-transected at the positive pinch site, and their proximal stumps were exposed to the retrograde neurotracer, Fluoro-Gold (F-G). Seventy-two hours later, the lumbar spinal cords and the L4 and L5 dorsal root ganglia (DRG) were harvested and evaluated. The incidence and the intensity of F-G labelling in DRG were significantly higher than in anterior horns (AH). These results demonstrated that sensory neurons were more dominant than motoneurons in nerve regeneration.

Unilateral sciatic nerve injury stimulates contralateral nerve regeneration.

Axonal outgrowth in tissue cultures was measured to determine whether unilateral peripheral nerve injuries affect contralateral nerve regeneration. The right sciatic nerves of young male Wistar rats were cut at mid-thigh level. Sham operation as a control was limited to the exposure of the nerve without cutting. At day 6 post-surgery, bilateral L5 dorsal root ganglia (DRG) with attached nerve stumps were resected and cultured. Axonal outgrowth from the nerve stump was measured in situ. The contralateral preparations showed longer outgrowths than controls. Therefore the conditioning effect was not merely restricted to the ipsilateral neurons but also affected undamaged sensory neurons of the contralaretal DRG.

Clinical significance of magnetic resonance imaging (MRI) for focal chondral lesions.

To evaluate the diagnostic potential of magnetic resonance imaging (MRI) and define its role, focal chondral lesions of the femoral surface of the tibiofemoral joint were examined. Full-thickness defects were well detected prospectively (93%) with conventional MRIs initially administered for observation reference of ligaments and menisci. Optimized MRIs, which included right-angled planes to the lesion surface and magnetization transfer contrast (MTC) sequences, delineated the size of lesions (R2 = 0.648,p < 0.0001) and the difference between full-and partial-thickness defects (88% in accuracy). A forward-tilt of 30 degrees to the femoral shaft was the average plane angle that afforded optimal visualization of the chondral lesions. Our findings advocate that routine MRIs are sufficient in detecting severe chondral lesions that require further examination, and the optimized images are highly useful in facilitating the recently developed therapeutic approaches and follow-up studies for articular cartilage defects.

Effectiveness of an insole with a lateral wedge for idiopathic osteonecrosis of the knee.

For the purpose of investigating the effect of an insole with a lateral wedge, we studied 30 patients (31 knees) aged from 46 to 78 years with idiopathic osteonecrosis of the knee for at least three years. The 18 knees treated with an insole (group I) were matched by age, gender, obesity index, area of lesion, femorotibial angle, stage, and clinical evaluation with 13 treated conservatively without an insole (group II). The clinical results, as rated by a knee score, improved significantly more in group I than in group II. Radiologically, the necrotic area and ratio decreased in group I, whereas in group II they increased. In advanced cases, with stage 4 or a femorotibial angle of more than 180 degrees, the use of an insole did not improve the clinical or radiological findings. The insole is a valuable method of conservative treatment for the early stages of osteonecrosis of the medial femoral condyle.

Transplantation of cartilage-like tissue made by tissue engineering in the treatment of cartilage defects of the knee.

We investigated the clinical, arthroscopic and biomechanical outcome of transplanting autologous chondrocytes, cultured in atelocollagen gel, for the treatment of full-thickness defects of cartilage in 28 knees (26 patients) over a minimum period of 25 months. Transplantation eliminated locking of the knee and reduced pain and swelling in all patients. The mean Lysholm score improved significantly. Arthroscopic assessment indicated that 26 knees (93%) had a good or excellent outcome. There were few adverse features, except for marked hypertrophy of the graft in three knees, partial detachment of the periosteum in three and partial ossification of the graft in one. Biomechanical tests revealed that the transplants had acquired a hardness similar to that of the surrounding cartilage. We conclude that transplanting chondrocytes in a newly-formed matrix of atelocollagen gel can promote restoration of the articular cartilage of the knee.

Diagnosis of a tear of the tibiofibular syndesmosis. The role of arthroscopy of the ankle.

In 52 patients we compared the accuracy of standard anteroposterior (AP) radiography, mortise radiography and MRI with arthroscopy of the ankle for the diagnosis of a tear of the tibiofibular syndesmosis. In comparison with arthroscopy, the sensitivity, specificity and accuracy were 44.1%, 100% and 63.5% for standard AP radiography and 58.3%, 100% and 71.2% for mortise radiography. For MRI they were 100%, 93.1% and 96.2% for a tear of the anterior inferior tibiofibular ligament and 100%, 100% and 100% for a tear of the posterior inferior tibiofibular ligament. Standard AP and mortise radiography did not always provide a correct diagnosis. MRI was useful although there were two-false positive cases. We suggest that arthroscopy of the ankle is indispensable for the accurate diagnosis of a tear of the tibiofibular syndesmosis.

The regeneration of sensory neurones in the reconstruction of the anterior cruciate ligament.

We examined whether somatosensory evoked potentials (SEPs) were detectable after direct electrical stimulation of injured, reconstructed and normal anterior cruciate ligaments (ACL) during arthroscopy under general anaesthesia. We investigated the position sense of the knee before and after reconstruction and the correlation between the SEP and instability. We found detectable SEPs in all ligaments which had been reconstructed with autogenous semitendinosus and gracilis tendons over the past 18 months as well as in all cases of the normal group. The SEP was detectable in only 15 out of 32 cases in the injured group, although the voltages in the injured group were significantly lower than those of the controls. This was not the case in the reconstructed group. The postoperative position sense in 17 knees improved significantly, but there was no correlation between it and the voltage. The voltage of stable knees was significantly higher than that of the unstable joints. Our findings showed that sensory reinnervation occurred in the reconstructed human ACL and was closely related to the function of the knee.

Induction of somatosensory evoked potentials by mechanical stimulation in reconstructed anterior cruciate ligaments.

We have determined whether somatosensory evoked potentials (SEPs) were detectable after direct mechanical stimulation of normal, injured and reconstructed anterior cruciate ligaments (ACLs) during arthroscopy. We investigated the position sense of the knee before and after reconstruction, and correlated the SEP with instability. Reproducible SEPs were detected in all 19 normal ACLs and in 36 of 38 ACLs reconstructed during a period of 13 months. Of the 45 injured ACLs, reproducible SEPs were detected in 26. The mean difference in anterior displacement in the SEP-positive group of the injured ACL group was significantly lower than that in the SEP-negative group. In the reconstructed group, the postoperative position sense was significantly better than the preoperative position sense. Our results indicate not only that sensory reinnervation occurs in the reconstructed ACL, but also that the response to mechanical loads can be restored, and is strongly related to improvement in position sense.

Reconstruction of the anterior cruciate ligament. Single- versus double-bundle multistranded hamstring tendons.

A total of 108 patients with unilateral instability of the knee, associated with rupture of the anterior cruciate ligament, was prospectively randomised for arthroscopic single- or double-bundle reconstruction of the ligament using hamstring tendons. The same post-operative rehabilitation protocol was used for all. The patients were followed up for a mean of 32 months (24 to 36). We measured the anterior laxity and joint position sense at different angles of flexion of the knee to determine whether both bundles in the double-bundle reconstruction contributed to the stability of the joint and proprioception. No significant difference was found between the two groups with regard to anterior laxity measured by the KT-2000 arthrometer with the knee at 20 degrees or 70 degrees flexion nor with regard to proprioception. A notchplasty was required less often in the double- compared with the single-bundle reconstruction. We did not find any advantage in a double-bundle as opposed to a single-bundle reconstruction in terms of stability or proprioception.

Antimicrobial activity of the diterpenes flexibilide and sinulariolide derived from Sinularia flexibilis Quoy and Gaimard 1833 (Coelenterata: Alcyonacea, Octocorallia).

The soft coral Sinularia flexibilis is rarely overgrown by bacteria and algae. Various studies have shown that it contains diterpenes that protect it from competitors and predators. However, of the many diterpenoids isolated from S. flexibilis, only sinulariolide has been studied for antibiotic properties. Samples of soft corals were collected from Orpheus Island and freeze-dried for chemical extraction and isolation of pure diterpenes. Antimicrobial activity of the diterpenes was determined using the disc assay method with antibiotics as controls and the minimum inhibitory concentrations of the diterpenes were determined using the Tube Dilution Technique. Two out of the five diterpenes tested (sinulariolide and flexibilide), showed marked antimicrobial activity and inhibited growth of Gram-positive bacteria. Flexibilide was effective even at concentrations as low as 5 ppm, whereas sinulariolide was effective at concentrations of 10 ppm. These compounds show potential as antibiotics.

Expression of cytokines after meniscal rasping to promote meniscal healing.

PURPOSE: We have developed a new surgical procedure of rasping a meniscal surface to repair a tear in the avascular zone. This procedure stimulates vascular induction to the tear, resulting in meniscal healing. The purpose of this study was to elucidate the mechanism of vascular induction and meniscal healing. TYPE OF STUDY: Randomized trial. METHODS: A full-thickness longitudinal tear of 5 mm in length was created in the avascular zone of the anterior segment of both medial menisci of rabbits. Meniscal rasping of about 0.5 mm in depth was then done on the femoral surface of the left meniscus from the parameniscal synovium to the inner portion including the longitudinal tear, and the right meniscus was left untreated as a control. After surgery, at 1, 7, 14, 28, 56, and 112 days, 4 rabbits were killed, both medial menisci were resected, and immunohistochemical staining with monoclonal antibodies was used to quantify expression of interleukin-1alpha (IL-1alpha), transforming growth factor-beta1 (TGF-beta1), platelet-derived growth factor (PDGF), and proliferating-cell nuclear antigen (PCNA) on the femoral surface of the menisci. A positive ratio of immunostaining was encountered. RESULTS: The positive ratio of IL-1alpha, TGF-beta1, PDGF, and PCNA on the rasped surface area reached its peak at 1, 7, 14, and 7 days, respectively, after surgery, and thereafter gradually declined. Although the time course of the positive ratio was different among these cytokines, the positive ratio on the rasped surface was significantly higher than that on the control surface at the early stage of the observation period. CONCLUSIONS: The cytokine network on the rasped meniscal surface appears to be the key to explaining the mechanism of vascular induction and meniscal healing by meniscal rasping.

A case of superficial peroneal nerve injury during ankle arthroscopy.

We report a case of superficial peroneal nerve (SPN) injury caused by ankle arthroscopy. A 20-year-old woman underwent arthroscopy on her right ankle because of chronic ankle pain after a sprain. After arthroscopy, the patient complained of pain on the dorsum of her right foot and felt a radiating pain from the anterolateral portal to the dorsomedial aspect of her foot. Eight months after arthroscopy, we found that a neuroma had developed on the intermediate dorsal cutaneous nerve, and performed neurolysis of the SPN. Her symptoms gradually decreased after surgery, and had disappeared by 45 months. To avoid such an injury of the SPN, the safest placement of the anterolateral portal is necessary and is, according to our previous anatomic study, 2 mm lateral to the peroneus tertius tendon.

Arthroscopic assessment of human cartilage stiffness of the femoral condyles and the patella with a new tactile sensor.

We measured the stiffness of the cartilage of the human femoral condyles via an ultrasonic tactile sensor under arthroscopic control. The stiffness and the degeneration of articular cartilage were assessed in 105 knees in 74 patients (39 men, 35 women, age: 9-72 years) who underwent arthroscopic observation or surgery. Twenty-five knees suffered from traumatic cartilage injury, 14 from osteochondritis dissecans, 13 from osteoarthritis, 11 from meniscal injury and six from ligamentous injury, bipartita patellae (three knees), and symptomatic plica synovialis (two knees). The degeneration of cartilage was classified according to Outerbridge's grading system. The relationships between the stiffness and the grade of cartilage degeneration, and gender were analyzed. The stiffness of grade I (softening) and II (fissuring less than 0.5 inches in length) was significantly lower than that of intact cartilage. In contrast, the stiffness of grade IV (exposed subchondral bone) was significantly higher than that of any other group. The cartilage stiffness of the patella in women was significantly lower than that in men. The tactile sensor was useful for determining the intraoperative stiffness of healthy and diseased human cartilage in all grades.

Computed tomographic evaluation of the position of the leg for mortise radiographs.

We investigated the most advantageous internal rotation angle of the leg for mortise radiographs. One hundred and twenty-eight feet of 64 healthy volunteers with no histories of ankle or foot pathology (72 feet of 36 males, 56 feet of 28 females) were examined. The subjects had an average age of 29 years (range, 19 to 51 years), average height of 167 cm (range, 157 to 181 cm), and average foot length of 25 cm (range, 23 to 27 cm). We obtained a plain axial view at the level of the central patella and 5 mm proximal to the tibial plafond using computed tomography, and investigated the inclination angle of the distal tibiofibular joint to a horizontal plane, regarding it as a mortise angle. The mean mortise angle was 19.1 +/- 5.0 degrees. However, two peaks were observed at around 15 degrees and 20 degrees. This indicated that the mean mortise angle of the males was 21.2 +/- 4.6 degrees, and the mean mortise angle of the females was 16.4 +/- 4.1degrees, with a significant difference between the males and the females' mortise angle (P < 0.0001). There was no correlation between the mortise angle and the height (P = 0.899 in the males, and P = 0.871 in the females), nor between the mortise angle and the foot length (P = 0.359 in the males, and P = 0.512 in the females). Therefore, we concluded that the internal rotation angle of the leg for mortise radiography should be generally set up at about 20 degrees on males and 15 degrees on females.

Adverse effects of saline neurolysis on a chronically compressed rat sciatic nerve.

We have evaluated the effect of saline neurolysis compared with a simple decompression procedure on chronically compressed sciatic nerves in rats. Eight months after the initiation of nerve compression within a silicone tube, rats were divided into three groups of 35. In group I, saline was injected subepineurially at the compressed segment of the nerve after removal of the tube (decompression plus saline neurolysis). The nerves in group II were treated by removal of the tube only (simple decompression). In group III the tubes were left in place. Adding saline neurolysis to decompression provided no histological, morphometric, electrophysiological, or vascular advantages up to four months, and even gave worse results than simple decompression. We conclude that saline neurolysis has no beneficial effect on a chronically compressed nerve and it is not recommended for clinical use.

The time-dependent difference of GAP-43 expression between sensory neurons and motoneurons after peripheral nerve transection.

The L5 dorsal root ganglion (DRG) cells and L5 anterior horn (AH) cells of rats were studied and examined immunocytochemically after transection of the sciatic nerve to find out whether there would be time-dependent differences in the increase of growth-associated protein (GAP-43) expression between sensory neurons and motoneurons. On the seventh day after transection at mid-thigh level, the levels of GAP-43 in the DRG cells significantly increased, while those in the AH cells began to increase gradually from the 14th day onward. Transection at the piriform muscle level induced a significant increase in immunoreactivity of GAP-43 on the third day in the DRG cells, and on the seventh day in the AH cells. These results showed that sensory neurons expressed GAP-43 immunoreactivity earlier than motoneurons after peripheral nerve transection regardless of the site, suggesting that sensory neurons might start to produce cytoskeletons for axonal elongation earlier than motoneurons after nerve transection.