Cement spacer loaded with antibiotics for infected implants of the hip joint.

It is difficult to treat infected implants of the hip joints. Such treatment involves immeasurable physical and psychological suffering of the patients. We used antibiotic-impregnated cement spacers in 17 cases of infection after total hip arthroplasty and bipolar arthroplasty with good clinical results. We thoroughly removed any foreign material and formed an antibiotic-impregnated cement spacer into a similar shape as that of the implants. A cement spacer enables high-concentration antibiotics to act on infected sites. Also, it can prevent leg length discrepancy and atrophy of bones or muscles. Although cement spacers have been reported to have problems regarding shape and strength, we achieved good results with a cement spacer mold in the present study. No recurring infection has been found at a mean follow-up period of 3 years and 2 months.

Ceramic total hip arthroplasty in the United States: safety and risk issues revisited.

The advantages of all-alumina bearings are superb wear resistance, stability, and inertness demonstrated over 3 decades. The disadvantage is a small risk for brittle fracture, as described in this paper. Surveying the latest ceramic hip series reported in recent journal articles or presented at the 6th World Biomaterials Congress, we found 11 studies representing more than 35,000 cases followed for 3 to 25 years. There were 24 reported fractures. A unique survey of hip complications in the 1990s found a fracture risk of approximately 1.4 per 1000 ceramic balls used in the United States. A company database holding more than 2.5 million records described the overall fracture risk as 1 per 10,000 cases. Initial use of ceramic cup inserts indicated a 2% to 3% incidence of chipping during surgery. Beginning in 1997, the number of ceramic-metal cup-locking cases entered into a US Food and Drug Administration ceramics database was more than 2400, with no fractures reported by the FDA in July 2003.

Apoptosis induced by chemotherapeutic agents involves c-Jun N-terminal kinase activation in sarcoma cell lines.

Molecular mechanisms underlying chemotherapeutic agent-induced apoptosis in sarcoma cells are not well known. Induction of apoptosis is regulated by several components including mitogen-activated protein kinases (MAPKs) comprising ERK, p38MAPKs, and c-Jun N-terminal kinase (JNK). In the present study, we examined whether activation of JNK is induced by the chemotherapeutic agents cis-diaminedichloroplatinum (cisplatin, CDDP) or doxorubicin (DXR), and whether the ectopic expression of constitutively active (MKK7-JNK1) or dominant-negative form of JNK (dnJNK) influenced apoptosis in response to the CDDP or DXR in sarcoma cell lines MG-63 and SaOS-2. The CDDP or DXR induced JNK activation in the both cell lines, as assessed by Western blotting using phosphospecific antibodies. A transient expression of the activated form of JNK sensitized the MG-63 and SaOS-2 cells to the drug-induced apoptosis, while dnJNK1 reduced the proportion of apoptotic cell death. Apoptosis was determined by flow cytometry using annexin-V Cy5. Collectively, our results indicate that JNK activation is involved in apoptotic cell death in sarcoma cell lines following stimulation with CDDP or DXR.

C-jun N-terminal kinase activation is required for apoptotic cell death induced by TNF-related apoptosis-inducing ligand plus DNA-damaging agents in sarcoma cell lines.

BACKGROUND: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in combination with a chemotherapeutic agent, cis-diammine dichloroplatinum (CDDP) or doxorubicin (DXR), has recently been demonstrated to result in enhanced apoptotic cell death in the sarcoma cell lines MG-63 and SaOS-2. DNA-damaging agents, such as CDDP induced sustained activation of c-Jun N-terminal kinase (JNK), probably leading to apoptosis. In the present study, whether JNK activation is involved in apoptotic cell death induced by combined treatment with CDDP/DXR and TRAIL was addressed. RESULTS: MG-63 or SaOS-2 cells overexpressing the dominant-negative (dn) form of JNK (dnJNK1) were established by transfection with dnJNK1 cDNA. Following stimulation with the chemotherapeutic agent CDDP or TRAIL, both MG-63 and SaOS-2 cells demonstrated enhanced cell death compared with stimulation by either agent alone, as assayed for apoptosis using annexin V staining or mitochondrial membrane potential using DiOC6 staining. Interestingly, partial inhibition of the cell death induced by the combined treatment with CDDP/DXR and TRAIL was found in MG-63 or SaOS-2 cells overexpressing dnJNK1, suggesting that JNK activation is required for the combined treatment. Moreover, induction of caspase-8 activation by TRAIL or TRAIL plus CDDP/DXR was substantially prevented by dnJNK. CONCLUSION: Efficient cell death induced by combined treatment with the chemotherapeutic agents CDDP/DXR and TRAIL is involved in JNK activation in the sarcoma cell lines MG-63 and SaOS-2. These results would be useful for treatment modalities of patients with sarcoma.

Results of total hip arthroplasty with bone graft and support ring for protrusio acetabuli in rheumatoid arthritis.

We evaluated 19 hips of 15 rheumatoid arthritis patients with protrusio acetabuli that had been surgically treated with total hip arthroplasty (THA) using a support ring; four hips were replaced with a TACT cup supporter, one hip with a Kerboull plate, six hips with a Ganz ring, and eight hips with a Müller ring. The average age was 60.2 years (range 48-75 years), and the average follow-up was 38 months (range 6-74 months). Two patients (three hips) died before the final follow-up, and two patients (two hips) underwent revision owing to loosening of the Ganz ring. Hip functions were rated according to the evaluation chart of hip joint functions of the Japanese Orthopaedic Association (JOA score). The mean total JOA score was 25.2 +/- 8.6 preoperatively and 55.6 +/- 8.7 postoperatively. Radiographically, 17 hips (minus the two revised hips) showed satisfactory incorporation of bone graft and no loosening of the support ring. The mean depth of protrusio acetabuli for these 17 hips was 3.5 +/- 4.1 mm before operation, 2.8 +/- 5.1 mm just after operation, and 2.3 +/- 3.9 mm at the final follow-up (no significant difference at the critical rate of 5%). Our study indicated the usefulness of THAs using a bone graft and a support ring in RA patients with protrusio acetabuli.

Observation of retrieved ceramic-on-ceramic articular surface: a case of revised total hip arthroplasty due to failure of the support ring.

We report the case of a 63-year-old woman who required revision surgery for ceramic-on-ceramic total hip arthroplasty (THA) due to failure of the support ring. We retrieved the ceramic cup and head, observed it macroscopically and measured it to determine its shape condition (sphere diameter, sphericity, and circularity) and surface condition (surface roughness by scanning electronic microscopy). Although abrasion was not found at the sliding surface of either the cup or head, it was observed at the edges of the cup and at one part of the head. We point out the risk of the edge contact and conclude the possibility of micro-motion between the cup and the head during walking or loading in vivo, and that contact had taken place at such parts.

Prophylaxis of C5 palsy after cervical expansive laminoplasty by bilateral partial foraminotomy.

BACKGROUND CONTEXT: It is known that postoperative motor palsy at the C5 level occurs with anterior decompression or posterior decompression and has a relatively good prognosis, but the pathogenesis and possible prophylactic measures of the palsy remain unknown. PURPOSE: The purpose of this study was to evaluate the effectiveness of bilateral partial foraminotomy for preventing C5 palsy from occurring after cervical decompression surgery. STUDY DESIGN: A retrospective review was performed concerning the risk factors of the C5 palsy based on the preoperative clinical findings. To investigate the prophylactic effect of the partial foraminotomy, we examined a difference of an incidence of the C5 palsy by performing concurrent partial foraminotomy with expansive laminoplasty. PATIENT SAMPLE: A total of 305 cases of cervical expansive laminoplasty performed for spondylotic myelopathy or ossification of the posterior longitudinal ligament were reviewed. METHODS: We analyzed 305 cases of cervical expansive laminoplasty to investigate the preoperative risk factors that may cause postoperative C5 palsy. To clarify the relationship of the foraminotomy and development of the C5 palsy, we examined 230 patients in whom foraminotomy could be confirmed by operative records. RESULTS: Of the 305 patients, postoperative C5 palsy occurred in 13 patients (4.3%): 10 patients had radicular pain (77%), and 8 patients had sensory disturbances (62%). We assessed all neurological findings and X-ray, computed tomography and electromyographic findings, but no statistical differences were found in any of the preoperative clinical findings relative to the occurrence of postoperative C5 palsy. For the open side, 108 cases underwent foraminotomy and 122 cases did not, whereas on the hinge side, 54 cases received foraminotomy and 176 cases did not. In order to investigate the prophylactic effect of foraminotomy, we totaled the open side and hinge side, and calculated the number of bone gutters: 162 gutters had concurrent foraminotomy and 298 gutters did not. Postoperatively, C5 palsy occurred in 1 gutter (0.6%) in the former group and in 12 gutters (4.0%) in the latter group (p<.05, Fisher's direct method). CONCLUSIONS: There were no specific risk factors among the preoperative clinical findings related to C5 palsy. Bilateral partial foraminotomy was effective for preventing C5 palsy.

Id3-mediated enhancement of cisplatin-induced apoptosis in a sarcoma cell line MG-63.

The molecular mechanism(s) underlying the resistance to cis-diamminedichloroplatinum (CDDP)-induced growth inhibition include DNA repair, apoptosis and cell cycle progression. Inhibitor of differentiation (Id) proteins, which belong to the group of helix-loop-helix proteins, regulate cell cycle progression, differentiation and apoptosis. We examined whether CDDP exposure modulates the expression pattern of Ids and whether ectopic expression of Ids influences CDDP-induced cell death. Cell growth was assessed by WST-8 assay kit. Reactive oxygen species (ROS) was evaluated by flow cytometry using dihydroethidium. MG-63 sarcoma cells were stimulated with CDDP for various times and Id expression was assessed by reverse transcription-polymerase chain reaction. CDDP induced a considerable transient up-regulation of Id3 mRNA, but not Id2, 1-2 h after stimulation. Enforced expression of Id3 caused the MG-63 sarcoma cells to be more sensitive to CDDP-induced growth inhibition, through generation of ROS and caspase-3 activation. Together, our results suggest that CDDP-induced cell death appears to involve Id3.

Micro-wear features on unique 100-Mrad cups: two retrieved cups compared to hip simulator wear study.

We studied the micro-wear phenomena of unique, extensively cross-linked polyethylene cups (cross-linked with 1,000 kGy-irradiation) that had been used briefly in Japan. Two retrievals (at 15 years) came from the Japanese "SOM" hip system (implanted 1971-78). These were compared to a set of 0 kGy and 500-1,500 kGy cups run in our hip simulator. The polyethylene cups that had not been cross-linked had the greatest wear. The worn areas had a burnished appearance and were clearly separated from the unworn region by a distinct ridge-line. The worn areas had lost all machine tracks, showed a large amount of UHMWPE 'flow', and long PE fibrils. The associated surface rippling was degraded. These features were considered synonymous with severe polyethylene wear. In contrast, the worn areas in the very cross-linked cups had a visibly matte surface and no ridge-line. Micro-examination showed that the machine tracks were still present. Ripple formations were less obvious than in the cups that were not cross-linked, polyethylene surface fibrils were scarcer and all the fibrils were much smaller than in the cups that were not crosslinked. Our two retrieved cups and the simulator cups confirmed the greater wear-resistance of very cross-linked polyethylene. It should also be noted that the SOM cup design and processing were unique and differed greatly from that of modern polyethylene cups.

Rhabdoid transformation of recurrent meningioma in the cervical cord: a case report.

We report a case of persistent local recurrence of rhabdoid meningioma in the cervical spinal cord. Recently, the meningioma has been reported to be undergoing rhabdoid transformation, but the clinical course is still unclear. Histopathological examination of the tumor showed that it was composed of both meningothelial cells and rhabdoid cells. At each recurrence of the tumor, the population of the rhabdoid cells had increased and the ability to grow had also increased, confirmed by the MIB-1 labeling index. This case showed that phenotypic change of the cells with "rhabdoid" morphology may affect meningiomas and that such changes are associated with aggressive biological and clinical behavior. This newly classified tumor should be recognized in the differential diagnosis of meningioma.

Stripe wear rates in alumina THR--comparison of microseparation simulator study with retrieved implants.

Alumina-on-alumina hip implants with microseparation were run in a hip simulator for comparison of the nonseparation simulator mode and retrievals. The 28-, 32-, and 36-mm Biolox-forte implants were run to 5 million cycles with the use of 50% newborn calf serum. Howmedica Osteonics Trident cups with titanium backing were used in all sets. In standard (STD) and microseparation (MSX) mode, the typical biphasic wear trend was evident, but the MSX test mode had much higher magnitudes. There was a 5-fold increase for run-in wear and up to a 35-fold increase in steady-state wear. The stripe wear on the ball formed early, but did not progress in grade beyond 0.6 Mc. The locations of the stripes were similar in retrieved and simulator balls. However, the stripes from the simulator were narrower than short-term retrievals and much narrower than some long-term retrievals. The long-term retrieved balls had a grade of wear greater than the simulators. In vivo a broader range of motion occurs and this may lead to the wider stripe observed on the retrievals. These observations suggested that simulators could produce the loading and kinematics similar to a patient walking but not necessarily the variety of motions possible in the in vivo situation.

The radiographic study in the relationship of the glenohumeral joint.

Accurate reproduction of anatomic relationship is important in non-constrained prosthetic arthroplasty. The accurate lateral glenohumeral offset, which indicates a parameter of the lever arm of the deltoid and supraspinatus muscles, is one of the most important elements in achieving the efficient shoulder functions after prosthetic reconstruction. However, to our knowledge, there has been no detailed study on the influence of minute changes in the neck shaft angle, within the normal range, on lateral glenohumeral offset. In this study, we evaluated the relationship between the neck shaft angle and various geometric measurement values in the glenohumeral joint. Radiographs of 471 shoulders without osseous lesions in the glenohumeral joint and greater tuberosity were reviewed. There were 265 males and 206 females, and a mean age was 53.5 years old. The final diagnosis was impingement syndrome in 269 patients, rotator cuff tear in 147, and control group in 55 patients. Eight parameters were measured on true anteroposterior radiographs. The lateral glenohumeral offset correlated with the radius of the curvature of the humeral head and the humeral head diameter. The neck shaft angle was not correlated with the offset value. However, when the offset value was divided by the humeral head diameter, to eliminate the affection of the size of the humeral head toward the offset, a correlation was observed with the neck shaft angle. Based on these correlations, we could obtain the equation of the lateral glenohumeral offset according to the neck shaft angle. Using the equation, when the neck shaft angle is decided, the lateral glenohumeral offset can be estimated based on the correlation between the parameters, which achieve the efficient shoulder functions after prosthetic components. Therefore, inaccurate determination of the neck shaft angle in the humeral head component design and selection may induce dysfunction of the abductor muscles.

Human DNA damage checkpoints and their relevance to soft tissue sarcoma.

Soft tissue sarcoma (STS) is a malignant neoplasm, arising in mesenchymal tissues, that is difficult to treat clinically because it can be highly resistant to chemo-radiotherapy. At present, the mechanism of that resistance remains unclear. Cell cycle checkpoints engender strict control of cell proliferation, arresting the cell cycle to provide time for repair or apoptosis when DNA damage is induced by unprogrammed extrinsic events. These pathways involve at least two checkpoints: one at the G1/S transition and one at the G2/M transition. The p53 gene, which is mutated in several malignant tumors, plays an important role in DNA repair at the G1/S transition; however, there is little information on the G2/M checkpoint in STS. In the present study, several proteins (phospho-p53, -cdc25, -cdc2, -Chk1 and -Chk2) involved in checkpoint pathways were investigated using immunohistochemistry in STS specimens. Most STSs maintain a well-preserved G2/M checkpoint despite the loss of the G1/S checkpoint (phospho-p53: 4.9% (2/41); -cdc25: 41% (17/41); -cdc2: 61% (25/41); -Chk1: 29% (12/41); -Chk2: 46% (19/41)). Furthermore, in a postoperative chemotherapy case the number of cells positive for phospho-cdc25 and -Chk2 was higher in a recurrent tumor than in the primary tumor (n = 7, P = 0.046 < 0.05, Wilcoxon signed-ranks test). These findings indicate that the G2/M checkpoint pathway is well preserved and might contribute to the chemotherapeutic resistance associated with STS.

Expression of cyclooxygenase-2 in chondroblastoma: immunohistochemical analysis with special emphasis on local inflammatory reaction.

To investigate the frequency and mechanism of the peritumoral inflammatory reaction in chondroblastoma, we evaluated the relationship between clinicoradiological findings and immunohistochemical expression of cyclooxygenase-2 (COX-2) in excised tumors. Twenty-one cases of chondroblastoma were studied. Imaging analysis was performed with radiographs and T1- and T2-weighted magnetic resonance images in all cases and with computed tomography scan and bone scintigraphy in some cases. Immunohistochemical study for COX-2 was carried out using formalin-fixed paraffin-embedded tissues. Periosteal reaction was observed in 6 cases (29%) and bone marrow edema in 15 cases (71%). Soft-tissue edema, joint effusion, and synovitis were found in 10 cases (48%), in 7 cases (33%), and in 9 cases (43%), respectively. Immunohistochemical expression of COX-2 in chondroblastoma cells was found in 15 of 21 cases (71%). The intensity of COX-2 immunoreactivity was correlated statistically with the presence of periosteal reaction, bone-marrow edema, soft-tissue edema, and synovitis. Our results indicate that activation of eicosanoid synthesis by COX-2 expression in the tumor itself is probably an important factor, inducing peritumoral inflammatory changes in chondroblastomas.

Clinical effectiveness of antibiotic-impregnated cement spacers for the treatment of infected implants of the hip joint.

It is difficult to treat an infected implant of the hip joints, as it requires long-term treatment and eventually may lead to amputation or arthrodesis, involving immeasurable physical and psychological suffering for the patient. We utilized antibiotic-impregnated cement spacers for 17 infections after total hip arthroplasty and bipolar arthroplasty with good clinical results. We thoroughly removed any foreign material and formed an antibiotic-impregnated cement spacer into a shape similar to that of the implants. This enabled high-concentration antibiotics to act on the infected sites. It also can prevent leg-length discrepancy and atrophy of bones or muscles. Although cement spacers have been reported to have problems regarding shape and strength, we achieved good results with cement spacer molds in the present study. All revision surgeries were performed using a two-stage procedure. No infection has recurred at a mean follow-up of 3 years 2 months.

Cementless total hip arthroplasty using porous-coated Biomet acetabular cups (Hexloc and Ringloc types).

This study examined the mid-term (more than 5 years) results of cementless total hip arthroplasty (THA) using Biomet acetabular cups (locking mechanism: Hexloc type or Ringloc type). A series of 58 patients (70 hips) who had undergone cementless THA at our department were available for inclusion in this study. The average age at surgery was 55.2 years, and the average follow-up was 6 years 10 months. Osteolysis occurred in five cases. In the group with osteolysis, the average annual linear wear was 0.18 mm/year, and in the group without osteolysis it was 0.10 mm/year. The higher linear wear rate in the osteolysis group was statistically significant compared to that in the nonosteolysis group. The age of the patient was closely related to polyethylene (PE) wear in the Hexloc group but not in the Ringloc group. In the Ringloc group there was no close correlation between the thickness of the PE liner and the average annual linear wear, whereas in the Hexloc group the thicker liner had significantly less annual linear wear. It was thought that PE wear of the Hexloc cup was more susceptible to the age of the patient at surgery and the PE thickness than that of the Ringloc cup owing to several structural differences, such as rotational stability and conformity between the metal cup and the PE liner.

Chemotherapeutic agents sensitize sarcoma cell lines to tumor necrosis factor-related apoptosis-inducing ligand-induced caspase-8 activation, apoptosis and loss of mitochondrial membrane potential.

Chemotherapeutic agents have been used for the treatment of patients with osteosarcoma (OS). However, inherent or acquired resistance to these agents is a serious problem in the management of OS patients. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered to induce apoptosis in a variety of cancer cells but not normal cells. In the present study, we examined whether chemotherapeutic agents enhance TRAIL-induced apoptosis in the sarcoma cell lines MG-63 and SaOS-2. Pretreatment with sub-toxic or slightly toxic concentrations of chemotherapeutic agents (cis-diammine dichloroplatinum, CDDP and doxorubicin, DXR) sensitized both cell lines to TRAIL-induced apoptosis, as assessed by the propidium iodide or Annexin V-Cy5 staining method. These cell lines expressed death receptors TRAIL-receptor 1 (TRAIL-R1) and TRAIL-R2, which were unaltered by treatment with CDDP, as assessed by flow cytometry. The decoy receptors TRAIL-R3 and -R4 were barely detected in both cell lines. CDDP down-regulated c-FLIP, tending to lower the activation threshold required for TRAIL-induced caspase-8 activation. The CDDP-pretreated cells indeed demonstrated more increased TRAIL-mediated caspase-8 activation, loss of mitochondrial membrane potential (DeltaPsi(m)), and apoptosis than untreated cells. Consequently, the activated caspase-8 might lead to either activation of effector caspases such as caspase-3 or loss in DeltaPsi(m). Both the increased caspase activation and mitochondrial dysfunction induced by combination of CDDP and TRAIL would contribute to enhanced apoptotic cell death. The results of the present study would be valuable for the design of novel treatment modalities for patients with OS.

Retrovirus-mediated transduction of TRAIL and chemotherapeutic agents co-operatively induce apoptotic cell death in both sarcoma and myeloma cells.

BACKGROUND: Resistance to multiple chemotherapeutic agents results from a variety of factors including a lack of apoptosis in tumor cells. To induce apoptosis in two types of tumor cells, RPMI-8226 and MG-63, a combination of chemotherapeutic agents and retroviral transduction of TRAIL was employed. MATERIALS AND METHODS: Both TRAIL-sensitive 8226 and -resistant MG-63 cells were pretreated with the anti-tumor agent doxorubicin or cisplatin for 24 hours, washed and then exposed to retroviral transduction with TRAIL for a further 24 hours, followed by assay for cell survival using a WST-8 kit. RESULTS: Doxorubicin or cisplatin sensitized both RPMI-8226 and MG-63 cells to TRAIL-induced death in a synergistic manner. This combined treatment was also effective in the MG-63 cells overexpressing Bcl-xL, which are resistant to multiple chemotherapeutic agents. CONCLUSION: A retroviral transduction of TRAIL in conjunction with anti-tumor agents could provide a new treatment modality for the treatment of patients with multiple-drug resistance.