An unusual cause for a painful Birmingham hip resurfacing.

The painful total hip arthroplasty requires careful evaluation and investigation. This is usually focused on the prosthesis and adjacent anatomical structures. We present a case report of a 64-year-old man who had a Birmingham hip resurfacing procedure for primary osteoarthritis. His hip pain worsened following the procedure and was under systematic investigation for this. Subsequent investigation for vascular disease revealed a total infrarenal aortic occlusion. An aortobifemoral bypass improved the hip pain and function dramatically, and the patient now has an excellent quality of life.

Preservation of the original femoral cement mantle during the management of infected cemented total hip replacement by two-stage revision.

The removal of all prosthetic material and a two-stage revision procedure is the established standard management of an infected total hip replacement (THR). However, the removal of well-fixed femoral cement is time-consuming and can result in significant loss of bone stock and femoral shaft perforation or fracture. We report our results of two-stage revision THR for treating infection, with retention of the original well-fixed femoral cement mantle in 15 patients, who were treated between 1989 and 2002. Following partial excision arthroplasty, patients received local and systemic antibiotics and underwent reconstruction and re-implantation at a second-stage procedure, when the infection had resolved. The mean follow-up of these 15 patients was 82 months (60 to 192). Two patients had positive microbiology at the second stage and were treated with six weeks of appropriate antibiotics; one of these developed recurrent infection requiring further revision. Successful eradication of infection was achieved in the remaining 14 patients. We conclude that when two-stage revision is used for the treatment of peri-prosthetic infection involving a THR, a well-fixed femoral cement mantle can be safely left in situ, without compromising the treatment of infection. Advantages of this technique include a shorter operating time, reduced loss of bone stock and a technically more straightforward second-stage procedure.

Proximal scaphoid rib graft arthroplasty.

We prospectively reviewed 14 patients with deficiency of the proximal pole of the scaphoid who were treated by rib osteochondral replacement arthroplasty. Improvement in wrist function occurred in all except one patient with enhanced grip strength, less pain and maintenance of wrist movement. In 13 patients wrist function was rated as good or excellent according to the modified wrist function score of Green and O'Brien. The mean pre-operative score of 54 (35 to 80) rose to 79 (50 to 90) at review at a mean of 64 months (27 to 103). Carpal alignment did not deteriorate in any patient and there were no cases of nonunion or significant complications. This procedure can restore the mechanical integrity of the proximal pole of the scaphoid satisfactorily and maintain wrist movement while avoiding the potential complications of alternative replacement arthroplasty techniques and problems associated with vascularised grafts and salvage techniques.

A highly potent inhibitor of cathepsin K (relacatib) reduces biomarkers of bone resorption both in vitro and in an acute model of elevated bone turnover in vivo in monkeys.

Cathepsin K is an osteoclast-derived cysteine protease that has been implicated as playing a major role in bone resorption. A substantial body of evidence indicates that cathepsin K is critical in osteoclast-mediated bone resorption and suggests that its pharmacological inhibition should result in inhibition of bone resorption in vivo. Here we report the pharmacological characterization of SB-462795 (relacatib) as a potent and orally bioavailable small molecule inhibitor of cathepsin K that inhibits bone resorption both in vitro in human tissue and in vivo in cynomolgus monkeys. SB-462795 is a potent inhibitor of human cathepsins K, L, and V (K(i, app)=41, 68, and 53 pM, respectively) that exhibits 39-300-fold selectivity over other cathepsins. SB-462795 inhibited endogenous cathepsin K in situ in human osteoclasts and human osteoclast-mediated bone resorption with IC50 values of approximately 45 nM and approximately 70 nM, respectively. The anti-resorptive potential of SB-462795 was evaluated in normal as well as medically ovariectomized (Ovx) female cynomolgus monkeys. Serum levels of the C- and N-terminal telopeptides of Type I collagen (CTx and NTx, respectively) and urinary levels of NTx were monitored as biomarkers of bone resorption. Administration of SB-462795 to medically ovariectomized or normal monkeys resulted in an acute reduction in both serum and urinary markers of bone resorption within 1.5 h after dosing, and this effect lasted up to 48 h depending on the dose administered. Our data indicate that SB-462795 potently inhibits human cathepsin K in osteoclasts, resulting in a rapid inhibition of bone resorption both in vitro and in vivo in the monkey. These studies also demonstrate the therapeutic potential of relacatib in the treatment of postmenopausal osteoporosis and serves to model the planned clinical trials in human subjects.

Constrained total hip arthroplasty in a paediatric patient with cerebral palsy and painful dislocation of the hip. A case report.

We describe a patient with cerebral palsy, of normal intelligence, who could not walk but who by the age of 16 had been successfully managed with a staged bilateral total hip arthroplasty using a constrained liner.

Popliteus tendon tenosynovitis.

This case report highlights an unusual cause of anterolateral knee pain. The popliteus muscle arises from three origins--that is, the lateral femoral condyle, the fibula head, and the lateral meniscus--and inserts into the proximal tibia above the soleal line. It may be subjected to a number of pathologies including tenosynovitis, acute calcific tendonitis, rupture, and even avulsion. In this case, the diagnosis of popliteus tendon tenosynovitis was not made from magnetic resonance imaging findings, but was confirmed and successfully treated during arthroscopic examination.

Increased osteoblastogenesis and decreased bone resorption protect against ovariectomy-induced bone loss in thrombospondin-2-null mice.

Although bone is composed primarily of extracellular matrix (ECM), the dynamic role that the ECM plays in regulating bone remodeling secondary to estrogen loss is relatively unexplored. Previous studies have shown that mice deficient in the matricellular protein thrombospondin-2 (TSP2-null) form excess endocortical bone; thus, we postulated that enhanced bone formation in TSP2-null mice could protect against ovariectomy (OVX)-induced bone loss. Wild-type (WT) OVX mice showed a significant loss of both midfemoral endocortical and proximal tibial trabecular bone, but OVX did not significantly alter TSP2-null bone. TSP2-null mice showed an increase in bone formation, as indicated by a 70% increase in serum osteocalcin two weeks post OVX and a two-fold increase in bone formation rate (BFR) five weeks post OVX as measured by dynamic histomorphometry. WT animals showed only a 20% increase in serum osteocalcin at two weeks and no change in BFR at five weeks. This increase in bone formation in TSP2-null OVX mice was accompanied by a three-fold increase in osteoprogenitor number. Although these results provide a partial explanation for the maintenance of bone geometry post-OVX, TSP2-null mice five weeks post-OVX also showed a significantly lower level of bone resorption than OVX WT mice, as determined by serum levels of the amino-terminal telopeptide of type I collagen (NTx). We conclude that the absence of TSP2 protects against OVX-induced bone loss by two complementary processes: increased formation and decreased resorption.

Ultrastructural quantification of cell death after injurious compression of bovine calf articular cartilage.

OBJECTIVE: It has been suggested that chondrocyte death by apoptosis may play a role in the pathogenesis of cartilage destruction in osteoarthritis, but the results of in-vivo and in-vitro investigations have been conflicting. To investigate further the cell death in our in-vitro model for traumatic joint injury, we performed a quantitative analysis by electron microscopy (EM) of cell morphology after injurious compression. For comparison, the TUNEL assay was also performed. DESIGN: Articular cartilage explant disks were harvested from newborn calf femoropatellar groove. The disks were subjected to injurious compression (50% strain at a strain rate of 100%/s), incubated for 3 days, and then fixed for quantitative morphological analysis. RESULTS: By TUNEL, the cell apoptosis rate increased from 7 +/- 2% in unloaded controls to 33 +/- 6% after injury (P=0.01; N=8 animals). By EM, the apoptosis rate increased from 5 +/- 1% in unloaded controls to 62 +/- 10% in injured cartilage (P=0.02, N=5 animals). Analysis by EM also identified that of the dead cells in injured disks, 97% were apoptotic by morphology. CONCLUSIONS: These results confirm a significant increase in cell death after injurious compression and suggest that most cell death observed here was by an apoptotic process.

A randomised trial of knife versus diathermy in pilonidal disease.

BACKGROUND: Pilonidal disease is a common debilitating condition. This prospective randomised study compared excision of pilonidal disease with a scalpel or diathermy with respect to operation time, postoperative pain, functional recovery and wound healing. PATIENTS AND METHODS: Patients undergoing surgery for pilonidal disease were randomised to excision by scalpel (group 1) or diathermy (group 2). Patients received regular peri-operative oral analgesia and a standardised general anaesthetic technique. Duration of operation was recorded. Following surgery, pain, analgesic requirements, sedation, nausea and vomiting scores and time to mobilise and time to complete healing were compared. RESULTS: Statistical significance between groups was obtained for five outcomes after 32 patients had been recruited; of these, 81% were admitted as emergencies with an abscess. The duration of surgery in group 2 was significantly less, postoperative pain scores and morphine requirements were lower and mobility was regained sooner. CONCLUSIONS: We advocate the use of diathermy needle rather than scalpel blade when undertaking excision of pilonidal disease in both acute and chronic patients.

A potent small molecule, nonpeptide inhibitor of cathepsin K (SB 331750) prevents bone matrix resorption in the ovariectomized rat.

Inhibition of the cyteine proteinase, cathepsin K (E.C. 3.4.22.38) has been postulated as a means to control osteoclast-mediated bone resorption. The preferred animal models for evaluation of antiresorptive activity are in the rat. However, the development of compounds that inhibit rat cathepsin K has proven difficult because the human and rat enzymes differ in key residues in the active site. In this study, a potent, nonpeptide inhibitor of rat cathepsin K (K(i) = 4.7 nmol/L), 5-(2-morpholin-4-yl-ethoxy)-benzofuran-2-carboxylic acid ((S)-3-methyl-1-(3-oxo-1-[2-(3-pyridin-2-yl-phenyl)-ethenoyl]-azepan-4-ylcarbanoyl)-butyl)-amide (SB 331750), is described, which is efficacious in rat models of bone resorption. SB 331750 potently inhibited human cathepsin K activity in vitro (K(i) = 0.0048 nmol/L) and was selective for human cathepsin K vs. cathepsins B (K(i) = 100 nmol/L), L (0.48 nmol/L), or S (K(i) = 14.3 nmol/L). In an in situ enzyme assay, SB 331750 inhibited osteoclast-associated cathepsin activity in tissue sections containing human osteoclasts (IC(50) approximately 60 nmol/L) and this translated into potent inhibition of human osteoclast-mediated bone resorption in vitro (IC(50) approximately 30 nmol/L). In vitro, SB 331750 partially, but dose-dependently, prevented the parathyroid hormone-induced hypercalcemia in an acute rat model of bone resorption. To evaluate the ability of SB 331750 to inhibit bone matrix degradation in vivo, it was administered for 4 weeks at 3, 10, or 30 mg/kg, intraperitoneally (i.p.), u.i.d. in the ovariectomized (ovx) rat. Both 10 and 30 mg/kg doses of compound prevented the ovx-induced elevation in urinary deoxypyridinoline and prevented the ovx-induced increase in percent eroded perimeter. Histological evaluation of the bones from compound-treated animals indicated that SB 331750 retarded bone matrix degradation in vivo at all three doses. The inhibition of bone resorption at the 10 and 30 mg/kg doses resulted in prevention of the ovx-induced reduction in percent trabecular area, trabecular number, and increase in trabecular spacing. These effects on bone resorption were also reflected in inhibition of the ovx-induced loss in trabecular bone volume as assessed using microcomputerized tomography (microCT; approximately 60% at 30 mg/kg). Together, these data indicate that the cathepsin K inhibitor, SB 331750, prevented bone resorption in vivo and this inhibition resulted in prevention of ovariectomy-induced loss in trabecular structure.

Localized wear of compomer restorative materials.

PURPOSE: To determine and compare the localized wear of six compomer restorative materials. MATERIALS AND METHODS: Ten specimens of Dyract, Dyract AP, F2000, Compoglass F, Elan and Hytac were prepared in a custom fixture and polished. A pretest surface profile was generated using an MTS 3-D surface profilometer and the specimens were subjected to 400,000 cycles in a Leinfelder wear machine equipped with a conical stylus tip to simulate localized wear. A post-test profile was generated and the before and after profiles were fitted and analyzed using AnSur 3-D software. The total volume loss and depth of the wear facet on each specimen was calculated and statistical analysis was accomplished (ANOVA and Tukey's test). RESULTS: Volume loss (mm3) was as follows: F2000, 0.027 +/- 0.002; Hytac, 0.007 +/- 0.023; Elan, 0.054 +/- 0.013; Compoglass F, 0.135 +/- 0.006; Dyract AP, 0.135 +/- 0.023; Dyract, 0.185 +/- 0.032. Maximum depth of the wear facets (microm) was as follows: F2000, 112.2 +/- 10.2; Hytac, 132.8 +/- 9.3; Elan, 144.3 +/- 23. 1; Compoglass F, 168.3 +/- 13.0; Dyract AP, 194.0 +/- 19.7; Dyract, 220.6 +/- 15.8. There was not a difference (P > 0.05) in volumetric loss between F2000 and Hytac or between Hytac and Elan. The volume loss and maximum depth of the wear facets of F2000, Hytac and Elan was significantly less (P< 0.05) than Compoglass F, Dyract AP and Dyract The results of this study indicate that there are significant differences in the in vitro wear rates of compomer materials.

The Epstein-Barr virus encoded latent membrane protein 2A augments signaling from latent membrane protein 1.

The frequent coexpression of the EBV-encoded latent membrane proteins LMP1 and LMP2A/B in virus-associated tumors suggests that these two proteins may cooperate in the transformation process. While LMP2A is unable to directly activate the NF-kappaB and AP-1 pathways, we found that coexpression of LMP2A with LMP1 resulted in a significant enhancement of LMP1-mediated activation of these pathways. This enhancement was found to be critically dependent on the tyrosine residues present within the ITAM motif (Y74/Y85) and, to a lesser extent, the tyrosine at position 112 (Y112). Subsequent analysis revealed that LMP2A is able to stabilize and modulate the turnover of LMP1 by extending its half-life. This ability does not require a direct physical interaction between the two proteins but rather, results from an indirect effect of LMP2A on the turnover of the LMP1 protein. This study highlights an important role for LMP2A as a modulator of LMP1 activity in epithelial cells.

Intracellular signaling pathways as a target for the treatment of rheumatoid arthritis.

Recent advances in our understanding of cellular and molecular mechanisms of rheumatoid arthritis have highlighted a critical role for interleukin-1 and tumor necrosis factor alpha. The quest for chemically amenable targets has recently led to the identification and characterization of the intracellular signaling pathways associated with these inflammatory cytokines. In particular the mitogen-activated protein kinase pathway, the nuclear factor kappaB pathway and the cross-talk between these offer several potential therapeutic opportunities for rheumatoid arthritis.

Preventing sexual risk behaviors among gay, lesbian, and bisexual adolescents: the benefits of gay-sensitive HIV instruction in schools.

OBJECTIVES: This study compared sexual risk behaviors of gay, lesbian, and bisexual (GLB) and heterosexual adolescents and evaluated associations between gay-sensitive HIV instruction and risk behaviors of GLB youths. METHODS: A random sample of high school students and HIV education teachers completed surveys. Self-reported risk behaviors of heterosexual and GLB adolescents were compared, with control for student and community demographic characteristics. Sexual risk behaviors of GLB youths in schools with and without gay-sensitive instruction were compared. RESULTS: GLB youths reported more substance use, high-risk sexual behaviors, suicidal thoughts or attempts, and personal safety issues than did heterosexual youths (P < .001). Among those who were sexually active, GLB youths reported more lifetime and recent sexual partners than did heterosexuals (P < .001), and more of them reported alcohol use before last sex (P < .01) and a history of pregnancy (P < .001). GLB youths in schools with gay-sensitive instruction reported fewer sexual partners, less recent sex, and less substance use before last sex than did GLB youths in other schools (P < .05). CONCLUSIONS: The findings document increased risk behaviors among GLB youths and demonstrate the potential benefits of providing gay-sensitive HIV instruction in schools.