Apoptosis and functional Fas antigen in rheumatoid arthritis synoviocytes.

OBJECTIVE: To determine whether apoptosis occurs in rheumatoid arthritis (RA) synoviocytes, and if this phenomenon is dependent on the Fas/Apo-1 pathway. METHODS: Apoptotic change in vivo was examined in RA synovial cells by several standard methods. The ability of cells to undergo Fas-induced apoptosis was determined in vitro. RESULTS: Typical apoptotic change was demonstrated in RA synovial cells by each method. Anti-Fas antibody induced apoptotic synovial cell death in vitro. CONCLUSION: This is the first reported study to demonstrate apoptosis in RA synovial cells. The findings indicate that rheumatoid synoviocytes undergo Fas-mediated apoptosis.

Analysis of Bankart lesion in the recurrent dislocation or subluxation of the shoulder.

The Bankart repair was used to restore anterior stability to 50 patients (51 shoulders) with recurrent dislocation or subluxation of the shoulder. The patients had preoperative diagnostic testing to determine the presence and extent of a Bankart lesion. At surgery, the Bankart lesion was carefully observed for its location, and extent of involvement of associated structures. The intraoperative findings of the severity of the Bankart lesion were compared with the preoperative data. The glenoidal fossa was considered like a clock, and the location and severity of the Bankart lesion was expressed by the hour of the clock. The Bankart lesion most frequently occurred from two o'clock to six o'clock in the right shoulder, and from six o'clock to ten o'clock in the left shoulder. The region of the glenohumeral joint at highest risk of exhibiting pathology after recurrent dislocation or subluxation of the shoulder was usually located from the central anterior edge of the glenohumeral joint to the inferior margin. Arthrogram with computed tomography was the most useful preoperative diagnostic test to demonstrate the Bankart lesion. The greatest number of inferior postoperative results were observed in patients with Bankart lesions of large size.

Light and electron microscopic study of remodeling and maturation process in autogenous graft for anterior cruciate ligament reconstruction.

We evaluated the remodeling process of autogenous patellar tendon graft for anterior cruciate ligament (ACL) reconstruction by means of light microscopic (LM) and electron microscopic (EM) examinations from the biopsy specimens obtained at the time of second-look arthroscopy. Twenty-one patients were examined at various times postoperatively (from 6 weeks to 15 months, mean 9.5 months), and the results were correlated with the morphology of normal patellar tendon and normal ACL. Our study showed that the graft was revascularized in the early postoperative period, fibroblastic remodeling took place, and the graft obtained gross similarity to the original ACL on their arthroscopic and LM appearances at approximately 1 year postoperatively. However, EM study showed that at both approximately 6 months and 1 year postoperatively the grafts consisted equally of active fibroblasts with a higher cytoplasm-to-nucleus ratio compared with normal ACL. Collagen fibrils of these grafts were of uniformly small diameter compared with normal patellar tendon and ACL. Our results with ultrastructural study suggest that the grafts were still immature even at 1 year postoperatively.

Treatment of hallux valgus by oblique osteotomy of the first metatarsal.

This paper describes a simple technique of oblique osteotomy of the first metatarsal for treatment of symptomatic hallux valgus deformity. The osteotomy is performed at a 30 degree angle from the long axis of the metatarsal shaft. The head of the metatarsal is then displaced laterally to provide correction of the hallux valgus. This is an uncomplicated procedure for the treatment of hallux valgus. From 1984 through 1989, 53 feet in 31 patients were treated with an oblique osteotomy of the first metatarsal. A total of 49 feet in 27 patients were followed up more than 2 years. The follow-up x-rays and clinical examinations revealed a good result in 43 feet. In six feet of three patients, all of whom had simultaneous oblique osteotomies of both the first and second metatarsals, a fair or poor result was obtained. It was learned that oblique osteotomy for hallux valgus greater than 40 degrees provided insufficient correction of the valgus angle or limitation of motion at the metatarsophalangeal joint of the great toe.

Meniscal repair using fibrin sealant and endothelial cell growth factor. An experimental study in dogs.

The effect of fibrin sealant and endothelial cell growth factor on the healing of defects of the avascular portion of canine menisci was investigated in 30 menisci of 15 adult mongrel dogs. The defects were treated in one of three ways: Group 1, the defect was left empty; Group 2, the defect was filled with fibrin sealant; and Group 3, the defect was filled with fibrin sealant and endothelial cell growth factor. The healing process was evaluated macroscopically and histologically at intervals of 1, 2, 6, 12, and 24 weeks. The average percentage of each defect that was filled with connective tissue was 5% in Group 1, 76.6% in Group 2, and 89.4% in Group 3. In the early phase of this repair, the extrinsic pannus-like tissue that contained many capillary vessels extended from the meniscosynovial junction into the defect. Subsequently, organized fibrous connective tissue was formed, which had changed to cartilaginous tissue at 12 to 24 weeks. The combination of fibrin sealant and endothelial cell growth factor enhanced the neovascularization and formation of granulation tissue, which accounted for the increased healing level in the avascular portion of the meniscus.

Immunomodulatory effects of therapeutic gold compounds. Gold sodium thiomalate inhibits the activity of T cell protein kinase C.

Previous studies have shown that the gold compounds, gold sodium thiomalate (GST) and auranofin (AUR), which are effective in the treatment of rheumatoid arthritis, inhibit functional activities of a variety of cells, but the biochemical basis of their effect is unknown. In the current studies, human T cell proliferation and interleukin 2 production by Jurkat cells were inhibited by GST or AUR at pharmacologically relevant concentrations. Because it has been documented that protein kinase C (PKC) is involved in T cell activation, the capacity of gold compounds to inhibit PKC partially purified from Jurkat cells was assayed in vitro. GST was found to inhibit PKC in a dose-dependent manner, but AUR caused no significant inhibition of PKC at pharmacologically relevant concentrations. The inhibitory effect of GST on PKC was abolished by 2-mercaptoethanol. To investigate the effect of GST on the regulation of PKC in vivo, the levels of PKC activity in Jurkat cells were examined. Cytosolic PKC activity decreased slowly in a concentration- and time-dependent manner as a result of incubation of Jurkat cells with GST. To ascertain whether GST inhibited PKC translocation and down-regulation, PKC activities associated with the membrane and cystosolic fractions were evaluated after phorbol myristate acetate (PMA) stimulation of GST incubated Jurkat cells. Translocation of PKC was markedly inhibited by pretreatment of Jurkat cells with GST for 3 d, but the capacity of PMA to down-regulate PKC activity in Jurkat cells was not altered by GST preincubation. The functional impact of GST-mediated downregulation of PKC in Jurkat cells was examined by analyzing PMA-stimulated phosphorylation of CD3. Although GST preincubated Jurkat cells exhibited an increased density of CD3, PMA-stimulated phosphorylation of the gamma chain of CD3 was markedly inhibited. Specificity for the inhibitory effect of GST on PKC was suggested by the finding that GST did not alter the mitogen-induced increases in inositol trisphosphate levels in Jurkat cells. Finally, the mechanism of the GST-induced inhibition of PKC was examined in detail, using purified PKC subspecies from rat brain. GST inhibited type II PKC more effectively than type III PKC, and also inhibited the enzymatic activity of the isolated catalytic fragment of PKC. The inhibitory effect of GST on PKC activity could not be explained by competition with phospholipid or nonspecific interference with the substrate. These data suggest that the immunomodulatory effects of GST may result from its capacity to inhibit PKC activity.

Weakness of thigh muscles in individuals sustaining anterior cruciate ligament injury.

The purpose of this study was to assess the quadriceps and hamstrings muscle strength deficits at different knee flexion angles (30 degrees and 60 degrees) in individuals who had sustained anterior cruciate ligament (ACL) injury, who had never had thigh muscle strengthening exercise. Isometric (0 degree/sec) and isokinetic (60 degrees/sec and 180 degrees/sec) torque measurements were performed on sixty-six patients (29 males and 37 females) with chronic ACL insufficiency. Significant strength deficits of the quadriceps and hamstrings muscles in injured knees were found at both 30 degrees and 60 degrees of knee flexion in three testing conditions (0 degree/sec, 60 degrees/sec, and 180 degrees/sec). In the comparison of torque production at 30 degrees and 60 degrees knee flexion angles, for the male group, significantly greater deficits of the quadriceps torque were found at 60 degrees knee flexion than at 30 degrees knee flexion in the isometric and isokinetic 60 degrees/sec testing modes. For the female group, significantly greater deficit of the quadriceps torque was found at 60 degrees knee flexion than at 30 degrees knee flexion only in isokinetic 60 degrees/sec. There was no significant difference of the hamstrings torque deficit between 30 degrees and 60 degrees knee flexion in any testing modes. In the comparison of isometric and two isokinetic testing modes (60 degrees/sec and 180 degrees/sec), for the male group, significantly greater deficits of the quadriceps torque were found at 30 degrees knee flexion in isokinetic 180 degrees/sec and at 60 degrees knee flexion in isokinetic 60 degrees/sec as compared to the isometric test. There was no statistical difference in the hamstrings torque values. For the female group, significantly greater deficits of the quadriceps and hamstrings torque were found at 30 degrees knee flexion in isokinetic 60 degrees/sec and at 60 degrees in isokinetic 60 degrees/sec and 180 degrees/sec as compared to the isometric test. It was concluded that long lasting instability without any muscle exercises may result in the weakness of not only the quadriceps muscle but also even hamstrings muscle, and that the quadriceps strength might be more susceptible to ACL insufficiency at 60 degrees knee flexion angle than at 30 degrees knee flexion angle, whereas, the hamstrings did not show any angular-specific torque deficits. These findings might resulted from characteristics of torque-curves of the quadriceps and hamstrings muscles.(ABSTRACT TRUNCATED AT 400 WORDS)

Ultrastructural morphology of early cellular changes in the synovium of primary synovial chondromatosis.

Synovial tissues taken from 13 cases of synovial chondromatosis (SC) were examined by light and electron microscopy. In three of the 13 cases, early cellular changes were observed by electron microscopy. Most of the foci were independently situated within an accumulation of fine, homogenous chondroid matrix in the sublining area of the synovium. Basal laminalike material was observed in these cells. Because this material was not apparent in the mature cartilage cells, the authors postulate that the basilaminar material affects cellular cytodifferentiation in SC during the initial phase of the disease. Ultrastructurally, these cells are morphologically similar to myofibroblasts. However, proliferation of paravascular cells with distinct basal laminae and activated secretory abilities was observed around some of the vessels. These paravascular cells may be the precursor cells of the prechondroblastic cells with basal laminalike material seen in SC.

[Mutilans type of rheumatoid arthritis].

In order to investigate the clinical and pathological features of arthritis mutilans, the clinical history, activity of inflammation, histological findings and treatment have been studied on the basis of follow-up of rheumatoid arthritis (RA) patients with arthritis mutilans. A high incidence of arthritis mutilans was observed in rheumatoid patients who have a younger onset, longer history and higher activity of RA without specific pathophysiological features. Joint destruction may further progress in arthritis mutilans despite intensive treatment with disease modifying anti-rheumatic drugs (DMARDs), and multi-joint replacement may be required in the patients with this type of arthritis.

A comparison of the bone mineral density of the vertebral bodies and the hip in elderly females with hip fractures. Assessment using dual photon absorptiometry.

The influence of decreasing bone mineral density with age and the occurrence of hip fractures in elderly females was investigated. Normal hips were studied in 287 healthy women whose ages ranged from 20 to 90 years old. The normal hip in 61 patients who had all suffered a femoral neck or intertrochanteric hip fracture, and were over 60 years old, were also studied and compared. The bone mineral density (BMD) of the lumbar vertebrae and the hip was measured with dual beam photon absorptiometry, for all patients. There was no correlation between the bone mineral density of the lumbar vertebral bodies, and the bone mineral density of the proximal femur. The peak bone mass in e lumbar vertebrae was seen in the thirties, but the peak bone mass in the hip was seen in the twenties. Bone mineral density in the lumbar vertebrae and in the hip was decreased in the patients who had sustained a hip fracture when compared to the control patients. The bone mineral density in the proximal femur was significantly reduced in patients who had sustained a hip fracture, especially in the region of Ward's triangle. These findings suggested that decreased bone mass in the hip at Ward's triangle may be correlated with the occurrence of hip fractures.

Signal transduction in glycosaminoglycan (GAG) synthesis by cultured chondrocytes and its inhibition by inflammatory cell-derived hydrogen peroxide.

Signal transduction in glycosaminoglycan (GAG) synthesis by chondrocytes has been studied. The activity of various subspecies of protein kinase C (PKC) in chondrocytes derived from rodent costal cartilage and bovine articular cartilage has been determined and the role of PKC in GAG synthesis as well as the possible interactions of PKC with calcium- or cyclic AMP (cAMP)-dependent systems in the synthesis of GAG. To investigate GAG synthesis in inflammatory conditions, the effects of hydrogen peroxide on PKC activity of the chondrocytes and PKC-mediated GAG synthesis have been studied. 12-O-Tetradecanoylphorbol-13-acetate (TPA), an activator of PKC, increased GAG synthesis in a dose-dependent fashion. This suggests that PKC up-regulates the synthesis of GAG in cultured chondrocytes. This increase was not significantly affected by simultaneous addition of the calcium ionophore, ionomycin, or dibutyryl cAMP (db-cAMP), a cAMP analogue. Ionomycin and db-cAMP, when used alone, did not significantly alter GAG synthesis by chondrocytes. Thus there appears to be no interaction between PKC and calcium- or cAMP-mediated systems in GAG synthesis. The increase in GAG synthesis induced by TPA was significantly (P less than 0.01) reduced by simultaneous addition of hydrogen peroxide (10(-6) M), without affecting cell viability. The activity of PKC in chondrocytes pretreated with 10(-6) M hydrogen peroxide was also significantly inhibited. Thus hydrogen peroxide which is generated by inflammatory cells may be important in suppression of GAG synthesis in inflammatory conditions.

Long-term results of knee synovectomy in pigmented villonodular synovitis.

1. Pigmented villonodular synovitis (PVS) commonly affects the knee as a monoarticular proliferative process. The etiology is not understood. 2. Partial synovectomy for localized PVS and wide synovectomy for diffuse PVS institute a favorable result, despite a rather high rate of recurrence at long-term follow-up. 3. Cases that involve bony erosion have a low incidence of recurrence but present an unsatisfactory prognosis even after curettage and wide synovectomy (postoperative progress of osteoarthritic changes).

Solitary paralysis of the triceps muscle due to trauma.

We report a rare solitary paralysis of the triceps muscle. The patient, an 18-year-old man who had had a work-related accident, sustained a severe contusion of the proximal posterolateral arm after being struck by a piece of lumber. This injury produced an extraordinary amount of soft-tissue swelling in the region of the trauma. After the accident it was noted that active flexion of the elbow was preserved, but active extension was absent. Three months after injury, surgical exploration of the radial nerve and its rami musculares to the three heads of the triceps muscle was undertaken. Dense adhesions were found fixing the rami musculares to the surfaces of the triceps muscle. Neurolysis of the rami musculares was performed, leading to complete recovery of the triceps muscle. The etiology of this isolated paralysis of the triceps muscle was determined to be dense adhesions compressing and compromising the function of the rami musculares to the three heads of the triceps muscle. These adhesions formed because of severe posttraumatic bleeding into the potential posterior humeral space, where the rami musculares are found.

Damage of cultured chondrocytes by hydrogen peroxide derived from polymorphonuclear leukocytes: a possible mechanism of cartilage degradation.

To study the mechanisms of chondrocyte damage, chondrocyte cytotoxicity as shown by chromium-51 release induced by polymorphonuclear leukocytes (PMNLs) was examined. PMNLs significantly enhanced chondrocyte cytotoxicity in the presence of phorbol dibutyrate. This chondrocyte damage was abolished by the addition of catalase, whereas superoxide dismutase and scavengers of hydroxyl radicals and protease inhibitors failed to reverse it. When cartilage matrix components such as hyaluronic acid and various proteoglycans were added to the PMNL-chondrocyte cultures, these components failed to affect the chromium-51 release. These results suggest that the increase in chondrocyte cytotoxicity is due to hydrogen peroxide generated by the PMNLs, and that cartilage matrix components do not prevent it. Hydrogen peroxide from PMNLs may therefore play an important role in cartilage degradation through direct damage of chondrocytes during inflammatory process.

The response of osteocytes to a lipid clearing agent in steroid-treated rabbits.

We studied the effect of a lipid clearing agent (clinofibrate) on the osteocytes of rabbits treated with corticosteroids. Thirty-one rabbits were divided into four groups: (A) steroid-treated with a normal diet, (B) steroid-treated and one a diet with added clinofibrate, (C) non-steroid-treated, on a diet with clinofibrate; and (D) non-steroid-treated on a normal diet. All the steroid-treated animals demonstrated hyperlipidaemia and fatty degeneration of the liver. Lipid-containing osteocytes were seen in the femoral heads of these animals. However, those which received clinofibrate (group B) had less severe lipidaemia, and less severe degeneration of the liver. In them, only the osteocytes around the haversian canals exhibited lipid inclusions. Clinofibrate appears to modify lipid metabolism, diminishing the steroid induced accumulation of lipids within osteocytes. This effect may protect against steroid-mediated osteonecrosis.

Anatomical study on the menisco-femoral ligaments of the knee.

The menisco-femoral ligaments are important accessory ligaments of the knee. They extend from the posterior horn of the lateral meniscus to the lateral aspect of the medial femoral condyle close to the femoral attachment of the posterior cruciate ligament. Most of the authors reported that in some cases these ligaments are absent. But in the 100 knees that we carefully examined, obvious menisco-femoral ligaments were identified in all of the specimens. When the anatomical relationship between the menisco-femoral ligaments and the lateral meniscus is considered, it can be easily speculated that the menisco-femoral ligaments draw the posterior horn of the lateral meniscus in anterior, medial and superior direction during flexion of the knee joint. Thus, the congruency between the lateral meniscus and femoral condyle and the stability of the knee joint increase.

Longitudinal ruptures of the peroneal tendons. A report of a rugby player.

Rupture of one or both peroneal tendons is rare. We present a case of longitudinal ruptures in both peroneus longus and brevis tendons. We obtained a very satisfactory clinical result with surgical debridement of the abnormal granulation tissue and proliferated synovial sheath.