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Biomedical subjects

Tomoyuki Saito

Publications and source records attributed to Tomoyuki Saito.

At least 19 recordsLinked to original sources

Results on total hip arthroplasties with femoral shortening for Crowe's group IV dislocated hips.

We performed total hip arthroplasties in 11 women with Crowe's group IV completely dislocated hips, with a mean age at surgery of 59.6 years and a mean follow-up of 65 months. In all cases, femoral shortening was achieved using step-cut osteotomy. All acetabular cups were placed in their anatomical locations. The mean Merle d'Aubigne hip score improved from 10.9 points to 16.9. There was no case of nonunion or malunion in the osteotomized site. Temporary numbness was observed in 2 hips, which subsided within 3 weeks without any treatment. One hip had to be revised 8 years after surgery because of aseptic loosening of the stem. Our study shows that total hip arthroplasty, incorporating step-cut femoral shortening, provides acceptable results for completely dislocated hip.

Adult↗

Inflammatory cytokines correlated with clinical outcome of temporomandibular joint irrigation in patients with chronic closed lock.

OBJECTIVE: This study investigated the correlation of clinical outcomes of temporomandibular joint (TMJ) irrigation with the occurrence and concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-8, IL-12, and IL-10 in the washed-out synovial fluid (SF) in patients with chronic closed lock (CCL) of the TMJ. STUDY DESIGN: Thirty-six patients underwent a visually guided TMJ irrigation (VGIR). SF samples were collected immediately before VGIR. The patients were divided into either successful (s-group; n = 25) or unsuccessful groups (u-group; n = 11). The detection rates and concentrations of each cytokine per milligram of total protein in the SF were measured, and then compared between the s- and u-groups. RESULTS: All of the investigated cytokines were detectable with various rates, concentrations, and combination patterns. The detection rate and concentrations of IL-6 were significantly higher in the u-group, and those of IL-10 were significantly higher in the s-group. CONCLUSIONS: The investigated cytokines were suggested to be involved in the pathophysiology of TMJ CCL. The results also suggest that IL-6 in the SF is an indicator of an unsuccessful outcome, and that IL-10 is a significant predictor of a successful outcome of TMJ irrigation for CCL.

Adult↗

Regulatory role of heme oxygenase 1 in inflammation of rheumatoid arthritis.

OBJECTIVE: To examine the expression and pathogenetic roles of heme oxygenase 1 (HO-1), an inducible heme-degrading enzyme with antiinflammatory properties, in rheumatoid arthritis (RA). METHODS: HO-1 expression in synovial tissue from patients with RA, patients with osteoarthritis, and patients with noninflammatory joint diseases was determined by immunoblotting and immunohistochemistry. Effects of various agents, such as hemin (a chemical inducer of HO-1), small interfering RNA (siRNA) specific for HO-1, HO-1 expression vector, and antirheumatic agents, on HO-1 expression in RA synovial cell lines were analyzed by real-time reverse transcription-polymerase chain reaction (PCR) and immunoblotting. Cytokine synthesis was evaluated by real-time PCR and enzyme-linked immunosorbent assay. RESULTS: HO-1 was expressed more abundantly in the lesions of synovial tissue from patients with RA than in those from the other patient groups. Hemin, auranofin, and HO-1 expression vector induced HO-1 and reduced expression of tumor necrosis factor alpha (TNFalpha) messenger RNA, lipopolysaccharide (LPS)-induced secretion of interleukin-6 (IL-6) and IL-8, and expression of cyclooxygenase 2 in the synovial cell lines. Treatment with HO-1-specific siRNA augmented the synthesis of TNFalpha, IL-6, and IL-8 and canceled the suppressive effects of auranofin on TNFalpha secretion. When hemoglobin, as a scavenger of carbon monoxide, was added to auranofin-treated synovial cell lines, LPS-dependent production of IL-6 and IL-8 was increased. CONCLUSION: Our data demonstrate that HO-1 is expressed in RA synovial tissues and plays a regulatory role in the development of inflammation. The pharmacologic effects of auranofin depend, in part, on the levels of HO-1, suggesting that HO-1 induction is a novel therapeutic strategy for RA.

Arthritis, Rheumatoid↗

Effects of vibration and hyaluronic acid on activation of three-dimensional cultured chondrocytes.

OBJECTIVE: To investigate the effects of vibration (Vib) and hyaluronic acid (HA) on 3-dimensional cultured cartilage. METHODS: Chondrocytes were obtained from metatarsophalangeal joints of freshly killed 6-month-old pigs. Twenty-four-well plates containing type I collagen sponge disks were used to culture samples. The frequency and the amplitude of the vibration of the well plate were 100 Hz and 0.5 nm, respectively. We produced 3-dimensional cartilage tissue using HA and vibration with collagen sponge as a carrier. Four different culture conditions were examined: a control HA-Vib- group, an HA-Vib+ group, an HA+Vib- group, and an HA+Vib+ group. Each group was cultured for 2 weeks. After culture days 3, 7, 10, and 14 (every 3.5 days), the levels of chondroitin 4-sulfate (C4S) and chondroitin 6-sulfate (C6S) isomers synthesized in each culture medium were measured. Histologic analysis, immunohistochemical analysis, and electron microscopic examination were performed. RESULTS: Mean C4S and C6S synthesis had increased rapidly after 7 days of culture and continued to increase thereafter. There were significant differences among the 4 groups (P < 0.01). Synthesis of both C4S and C6S was most abundant in the HA+Vib+ group and the lowest in the HA-Vib- group. After 1 and 2 weeks of culture, the chondrocytes had formed stratified structures on the collagen sponges in all groups, although the thickest structure was observed in the HA+Vib+ group and the thinnest in the HA-Vib- group. Under immunofluorescence, the HA+Vib+ group exhibited the strongest chromatic features. Under electron microscopy, the chondrocytes in the HA+Vib+ group exhibited many long and slender prominences on their surface, and extracellular substance could be observed associated with the cells. CONCLUSION: Our results indicate that the combination of vibration and HA activates the production of proteoglycan in 3-dimensional cultured chondrocytes and stimulates MAPK and beta-catenin. This suggests that some mechanoreceptors for vibration exist on the plasma membrane of chondrocytes and activate the intracellular signal transduction system.

Animals↗

Identification of novel citrullinated autoantigens of synovium in rheumatoid arthritis using a proteomic approach.

Recently, autoantibodies to some citrullinated autoantigens have been reported to be specific for rheumatoid arthritis (RA). However, an entire profile of and autoimmunity of the citrullinated proteins have been poorly understood. To understand the profile, we examined citrullinated autoantigens by a proteomic approach and further investigated the significance of citrullination in antigenicity of one of the autoantigens. Specifically, we detected citrullinated autoantigens in synovial tissue of a patient with RA by two-dimensional electrophoresis and Western blotting by using pooled sera from five patients with RA and anti-citrulline antibodies. After identifying the detected autoantigens by mass spectrometry, we investigated the contribution of citrullination to autoantigenicity by using a recombinant protein with or without citrullination on one of the identified novel citrullinated autoantigens. As a result, we found 51 citrullinated protein spots. Thirty (58.8%) of these spots were autoantigenic. We identified 13 out of the 30 detected citrullinated autoantigenic proteins. They contained three fibrinogen derivatives and several novel citrullinated autoantigens (for example, asporin and F-actin capping protein alpha-1 subunit [CapZalpha-1]). We further analyzed the contribution of citrullination to autoantigenicity in one of the detected citrullinated autoantigens, CapZalpha-1. As a result, frequencies of autoantibodies to non-citrullinated CapZalpha-1 were 36.7% in the RA group tested, 10.7% in the osteoarthritis (OA) group, and 6.5% in healthy donors. On the other hand, those to citrullinated CapZalpha-1 were 53.3% in the RA group, 7.1% in the OA group, and 6.5% in the healthy donors. This shows that autoantigenicity of citrullinated or non-citrullinated CapZalpha-1 is relevant to RA. The antibody titers to the citrullinated CapZalpha-1 were significantly higher than those to the non-citrullinated CapZalpha-1 in 36.7% of patients; however, the other patients showed almost equal antibody titers to both citrullinated and non-citrullinated CapZalpha-1. Therefore, the autoantibodies would target citrulline-related and/or citrulline-unrelated epitope(s) of CapZalpha-1. In conclusion, we report a profile of citrullinated autoantigens for the first time. Even though citrullination is closely related to autoantigenicity, citrullination would not always produce autoantigenicity in RA. Citrullinated and non-citrullinated autoantigens/autoepitopes would have different pathological roles in RA.

Adult↗

One-year clinical course following visually guided irrigation for chronic closed lock of the temporomandibular joint.

OBJECTIVE: This study aimed to explore the clinical course following visually guided irrigation (VGIR) for chronic closed lock (CCL) of the temporomandibular joint (TMJ) as well as the factors of importance for clinical outcome. Evaluation emphasis was placed on the period needed for the patients to reach the success criteria. STUDY DESIGN: Sixty-one patients with unilateral CCL comprised the study group. The cumulative success rate of VGIR and the additional surgical treatments following VGIR were studied. The 61 patients were divided into either the good outcome (g) group or poor outcome (p) group on the basis of whether they reached the success criteria within 3 months postoperatively, and clinical and arthroscopic factors were correlated with the clinical outcome of VGIR. RESULTS: The cumulative success rate of VGIR increased up to the 6-month follow-up (success rate of 72.1%) but did not change after that point in time. A repeated VGIR (success rate of 87.5%) was performed in 8 patients. Open TMJ surgery (success rate of 87.5%) was performed in 8 patients, 7 of whom had an interfering condylar osteophyte. A pronounced reduction of preoperative painless range of mandibular motion (P-ROM) and advanced osteoarthritis (OA) were more frequently found in the p-group than in the g-group. The multivariate adjusted odds ratio showed that a decreased preoperative P-ROM was significantly predictive for a poor outcome of VGIR. CONCLUSIONS: The efficacy of VGIR is clinically acceptable as an initial surgical treatment for TMJ CCL. A 6-month follow-up period ought to be sufficient for outcome assessment of VGIR. A pronounced reduction of preoperative P-ROM should be considered as a risk factor for delay of the postoperative improvement, and OA changes may sometimes affect the clinical outcome of VGIR.

Adult↗

Alteration in risk factor accumulations of acute myocardial infarction during the last one decade: analysis of patients admitted in Coronary Care Unit.

The present study was undertaken to determine accumulation of risk factors in acute myocardial infarction during two periods of 2002 and 1990-1991. We collected 173 and 153 patients with acute myocardial infarction in 2002 and 1990-1991, respectively, and analyzed the history of multiple risk factors, including diabetes mellitus, impaired glucose tolerance, hyperlipidemia, hypertension and obesity, and laboratory findings. The numbers and their percentages of all the risk factors increased in 2002 compared with 1990-1991. According to plasma glucose level, the patients who had type 2 diabetes mellitus, and impaired fasting glucose or impaired glucose tolerance had increased markedly from 41 to 65%. Multiple accumulation of risk factors had increased during the last one decade, and only one or no risk factor per se was not the case in the patients with acute myocardial infarction. Hyperlipidemia and hypertension became fairly controlled in the patients, but not hyperglycemia in type 2 diabetes mellitus in the period of 2002. These findings may indicate that increased multiple accumulation of risk factors accelerates the occurrence of acute myocardial infarction in 2002 as compared to 1990-1991.

Blood Glucose↗

Hypertonicity regulates the aquaporin-2 promoter independently of arginine vasopressin.

BACKGROUND: Aquaporin-2 (AQP-2) is an arginine vasopressin (AVP)-regulated water channel in kidney collecting duct cells. The present study was undertaken to determine whether a change in tonicity could directly regulate the AQP-2 gene in an in vitro experiment. METHODS: Various fragments of the 5'-flanking region of the murine AQP-2 gene up to -9.5 kb were cloned into a luciferase (Luc) reporter plasmid, and they were transiently transfected into Madin-Darby canine kidney cells. RESULTS: Hypertonicity significantly increased the Luc activity of the constructs containing >6.1 kb of the 5'-flanking region of the AQP-2 gene (-6.1AQP2). However, promoter regions <4.3 kb in length containing the tonicity-responsive enhancer (TonE) at bp -570 to -560 were not stimulated by hypertonicity. The TonE-deleted construct which contains -9.5 to -1.1 kb of the 5' side of the AQP-2 gene, 8.4AQP2, was also stimulated by hypertonicity. Mitogen-activated protein (MAP) kinase inhibitors SB203580 and U0126 did not affect the Luc activity of -6.1AQP2 induced by hypertonicity. In addition, the vector expressing dominant-negative TonE-binding protein (TonEBP) did not affect the hypertonicity-induced Luc activity of -6.1AQP2. The Luc activity of -6.1AQP2 was stimulated by the overexpression of TonEBP. Hypertonicity further increased the Luc activity of -6.1AQP2 under the overexpression of TonEBP. CONCLUSION: These findings indicate that hypertonicity regulates AQP-2 promoter activity via an AVP-independent mechanism, and that the tonicity-responsive element resides between the -6.1 and -4.3 kb 5'-flanking region of the AQP-2 gene, in which the structure and mechanism of response to hypertonicity could be distinct from those of TonE.

5' Flanking Region↗

Repair of articular cartilage defect by autologous transplantation of basic fibroblast growth factor gene-transduced chondrocytes with adeno-associated virus vector.

OBJECTIVE: To examine the effects of basic fibroblast growth factor (bFGF) gene-transduced chondrocytes on the repair of articular cartilage defects. METHODS: LacZ gene or bFGF gene was transduced into primary isolated rabbit chondrocytes with the use of a recombinant adeno-associated virus (AAV) vector. These gene-transduced chondrocytes were embedded in collagen gel and transplanted into a full-thickness defect in the articular cartilage of the patellar groove of a rabbit. The efficiency of gene transduction was assessed according to the percentage of LacZ-positive cells among the total number of living cells. The concentration of bFGF in the culture supernatant was measured by enzyme-linked immunosorbent assay to confirm the production by bFGF gene-transduced chondrocytes. At 4, 8, and 12 weeks after transplantation, cartilage repair was evaluated histologically and graded semiquantitatively using a histologic scoring system ranging from 0 (complete regeneration) to 14 (no regeneration) points. RESULTS: LacZ gene expression by chondrocytes was maintained until 8 weeks in >85% of the in vitro population. LacZ-positive cells were found at the transplant sites for at least 4 weeks after surgery. The mean concentration of bFGF was significantly increased in bFGF gene-transduced cells compared with control cells (P < 0.01). Semiquantitative histologic scoring indicated that the total score was significantly lower in the bFGF-transduced group than in the control group throughout the observation period. CONCLUSION: These results demonstrated that gene transfer to chondrocytes by an ex vivo method was established with the AAV vector, and transplantation of bFGF gene-transduced chondrocytes had a clear beneficial effect on the repair of rabbit articular cartilage defects.

Animals↗

Down-regulation of basic fibroblast growth factor production from cartilage by excessive mechanical stress.

BACKGROUND: We examined the effect of excessive stress on the production of basic fibroblast growth factor (bFGF) by bovine cartilage. METHODS: Bovine articular carpal bone was harvested and cut into 1 cm thick slices horizontally. Continuous compressive stress (0, 2, 20 MPa) was loaded on the cartilage of the carpal bone using a stainless-steel cylinder with a diameter of 8 mm for 1 h. The slices were cultured immediately after compression, and the supernatant of the culture medium was collected for bFGF and nitric oxide (NO) measurement. Interleukin-4 (IL-4) or N(G)-monoethyl-L: -arginine (L: -NMEA) was added to the culture medium in some experiments. RESULTS: Basic FGF production was significantly increased after 36 h of cultivation without mechanical stress (0.40 +/- 0.03 microg/ml). In contrast, the bFGF concentration was not increased by compressive stress of 20 MPa after 36 h of cultivation. An NO inhibitor, L: -NMEA, did not alter the effect of compressive stress on the production of bFGF. IL-4 reduced the production of bFGF by cartilage with or without mechanical stress. CONCLUSIONS: Excessive stress on cartilage inhibits the production of bFGF in an NO-independent manner, and IL-4 plays an important role in the reduction of bFGF.

Animals↗

Close association of hypoadiponectinemia with arteriosclerosis obliterans and ischemic heart disease.

Adiponectin is an adipose-derived cytokine, and it is suggested that hypoadiponectinemia increases the prevalence of ischemic heart disease (IHD). The present study was undertaken to determine serum adiponectin levels in patients with arteriosclerosis obliterans (ASO) and IHD. Forty-nine patients with ASO and 49 age-, sex-, and body mass index-matched control subjects were examined. The diagnosis of ASO was derived from an ankle brachial index of less than 0.90 and stenotic or obstructive change in angiogram. Ischemic heart disease was diagnosed by ischemic or stenotic change in ECG, treadmill, or coronary angiogram. Serum adiponectin level was 8.6 +/- 0.9 microg/mL in the patients with ASO, a value significantly less than that of 12.4 +/- 1.0 microg/mL in the control subjects ( P < .01). Next, we subgrouped the subjects into 4 groups according to the presence of ASO and IHD. Serum adiponectin levels were 9.4 +/- 1.5 and 10.2 +/- 1.6 microg/mL in the subjects with ASO (n =23) and those with IHD (n = 13), respectively. It was further reduced to 7.9 +/- 1.2 microg/mL in the subjects having both ASO and IHD (n = 26), a value significantly less than that of 13.2 +/- 1.4 microg/mL in the control subjects (n = 36; P < .05). Serum high-density lipoprotein cholesterol was significantly less in the subjects with ASO than in the control subjects (42.1 +/- 1.7 vs 48.5 +/- 2.0 mg/dL; P < .05), but there were no differences in blood pressure, total cholesterol, low-density lipoprotein cholesterol, triglyceride, and uric acid levels. The present results indicate that a reduction in serum adiponectin level is associated with the prevalence and magnitude of systemic atherosclerosis including IHD and ASO.

Adiponectin↗

Elevation of serum adiponectin levels in Basedow disease.

The present study was undertaken to determine whether thyroid hormone affects serum adiponectin levels in the patients with Basedow disease. Sixty-four patients with Basedow disease were examined; 32 patients had hyperthyroid state and 32 patients had euthyroid state who had been treated with antithyroid drugs. In addition, 30 age- and sex-matched subjects served as a control. Serum adiponectin, free T4, free T3, thyroid-stimulating hormone, and thyroid-stimulating hormone receptor antibody (TRAb) were measured. Serum adiponectin levels were 12.9+/-1.6 microg/mL in the hyperthyroid state, a value significantly greater than that of 8.2 +/- 0.5 microg/mL in the euthyroid state (P<.05) and that of 8.6+/-0.7 microg/mL in the control subjects (P<.05). Serum adiponectin levels had positive correlations with either of serum free T4 (r=0.453, P<.001), free T3 (r=0.47, P< .001), or TRAb (r= 0.491, P<.001), but not with body mass index. Multiple regression analysis showed TRAb had the strongest contribution to serum adiponectin concentration in the patients with Basedow disease. The present findings indicate that hyper-adiponectinemia is closely associated with increases in serum thyroid hormone levels and TRAb in Basedow disease.

Adiponectin↗

Repair of articular cartilage defect by intraarticular administration of basic fibroblast growth factor gene, using adeno-associated virus vector.

The objective of this study was to establish the potency of adeno-associated virus (AAV) as a viral vector to transport the basic fibroblast growth factor (bFGF) gene into synovial tissue, and to evaluate the consequent repair of articular cartilage defects. In the in vitro study, LacZ- and bFGF-encoding genes were transduced into rabbit synoviocytes by recombinant adeno-associated virus (AAV) vector, and the cells were cultured for 2 weeks. The percentage of successfully transduced LacZ-positive cells was assessed by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside staining, and the concentration of bFGF in the culture supernatant was confirmed by bFGF-specific enzyme-linked immunosorbent assay. In the in vivo study, 12- to 14-week-old Japanese white rabbits (all female) were used. AAV-bFGF was administered into an artificially created full-thickness defect (5 mm in diameter and 3 mm deep) in the patellar groove of the distal femur. Cartilage repair was subsequently monitored at 4, 8, and 12 weeks, by macroscopic and histological examination, and results were graded on the basis of semiquantitative scores. lacZ gene expression in synoviocytes reached more than 93% within the first 2 weeks, and the mean bFGF concentration in the culture supernatant of the bFGF gene-transduced group was significantly increased (p < 0.01). Semiquantitative macroscopic and histological assessment indicated that the average score was significantly better in the bFGF-transduced group throughout the observation period, suggesting better cartilage repair. These results demonstrate that gene transfer into synoviocytes, using the AAV vector, was a potent method of gene transduction. Moreover, after intraarticular administration of AAV-bFGF, constant expression of bFGF in the knee joints resulted in substantial cartilage regeneration that, with further long-term study, could possibly merit consideration for clinical application.

Animals↗

Lavendustin A enhances axon elongation in VHL gene-transfected neural stem cells.

Axonal elongation is necessary for neuronal regeneration of the spinal cord after spinal injury. Recently neural stem cells have been proposed as hopeful graft donors for regeneration of the central nervous system. However, most grafted stem cells are not able to differentiate into neurons, and grafted stem cells cannot usually grow axons. Here, we show the effect of the protein tyrosine kinase inhibitor lavendustin A on axonal growth of neurons differentiated from neural stem cells obtained from adult rat hippocampal cells transfected with the von Hippel-Lindau (VHL) gene. Significantly greater axonal outgrowth was observed for the transfected cells treated with the inhibitor than for those not so treated. Thus, protein-tyrosine kinase inhibition is effective for axonal outgrowth of neurons differentiated from neural stem cells and may prove to be useful for neuronal regeneration via transplanted stem cells, particularly in the case of spinal cord injuries.

Animals↗

Development of novel steroid sulfatase inhibitors; II. TZS-8478 potently inhibits the growth of breast tumors in postmenopausal breast cancer model rats.

In postmenopausal breast cancer tissue, steroid sulfatase (STS) activity is high and much estrone sulfate also exists; these facts reveal that estrone sulfate may be involved in the growth of breast cancer as an estrogen source. Steroid sulfatase is an enzyme, which catalyzes hydrolysis from estrone sulfate to estrone, and the development of steroid sulfatase inhibitors is expected as novel therapeutic drugs for postmenopausal breast cancer. We have developed a novel compound 2',4'-dicyanobiphenyl-4-O-sulfamate (TZS-8478), which has potent steroid sulfatase-inhibitory activity and exhibits no estrogenicity in vitro and in vivo. To elucidate its usefulness as a therapeutic drug for postmenopausal breast cancer, we examined the breast cancer cell proliferation- and breast tumor growth-inhibitory activity of TZS-8478 in postmenopausal breast cancer model rats. TZS-8478 dose-dependently suppressed the estrone sulfate-stimulated proliferation of MCF-7 cells. Regarding nitrosomethylurea (NMU)-induced postmenopausal breast cancer models, furthermore, TZS-8478 (0.5 mg/kg per day) markedly inhibited the estrone sulfate-stimulated growth of breast tumors similarly to estrone sulfate-depletion. TZS-8478 completely inhibited steroid sulfatase activity in tumor, uterus and liver, and also markedly lowered plasma concentrations of estrone and estradiol. The above mentioned results suggested that TZS-8478 may be useful as a therapeutic drug for estrogen-dependent postmenopausal breast cancer.

Animals↗

Fifteen to twenty-eight years' follow-up results of high tibial valgus osteotomy for osteoarthritic knee.

A long-term follow-up study was performed on 75 knees of 53 patients after high tibial valgus osteotomy. The earlier results have previously been reported. There were 15 knees in 11 men and 60 knees in 42 women. The follow-up period ranged from 15 to 28 years with a mean of 19 +/- 3 years. The age at osteotomy ranged from 46 to 73 years with a mean of 59.6 +/- 6.7 years. The diagnosis was medial compartmental osteoarthritis (OA) in 68 knees (46 patients) and spontaneous osteonecrosis of the medial femoral condyle in 7 knees (7 patients). Valgus osteotomy was performed above the tibial tuberosity, with removal of a laterally based wedge in all cases, aiming for anatomical valgus angulation of 10 degrees . The American Knee Society Score showed a Knee Score of 37 +/- 20 and a Function Score of 38 +/- 16 preoperatively and 87 +/- 13 and 80 +/- 19 at the final 15 to 28 years' follow-up. The femoro-tibial angle in standing was 186 +/- 6.5 degrees (6 degrees of anatomical varus angulation) before and 171 +/- 7.5 degrees (9 degrees of anatomical valgus angulation) at final follow-up (p < 0.0001), with no apparent loss of limb alignment.

Aged↗

Mechanisms of failure of total hip replacements: lessons learned from retrieval studies.

The value of implant retrieval analysis in orthopaedic surgery has been well recognized. Prosthetic devices retrieved for cause at revision surgery (for implant failure) or devices retrieved postmortem from patients with clinically successful reconstructions provide a unique set of specimens that can be studied to evaluate the effect of the implant on the host environment and the effect of the host environment on the implant. A systematic analysis of retrieved components, in combination with histologic, radiographic, and clinical data can provide valuable insights into the mechanisms of failure of the biomaterials used in joint replacement applications. From the hip implant retrieval studies reported to date, it has been established that the local reaction to particulate wear debris initiates the formation of a granulomatous tissue that ultimately invades the bone-implant interface and results in aseptic loosening. Cement mantle defects, noncircumferential porous coatings, and screw holes can serve as preferential access pathways for the progression of this granulomatous process yielding distinctive patterns of implant loosening and osteolysis. Continued surveillance of retrieved devices is strongly recommended to deepen our understanding of implant failure mechanisms and to evaluate the impact of newer designs and materials on the performance of joint replacement devices.

Animals↗