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Impending and complete pathologic fractures often necessitate surgical fixation. Traditional orthopedic implants are commonly used, achieving clinically acceptable outcomes, but their metallic composition can impair radiographic evaluation and affect radiation treatments. Recognition of these concerns led to the development of radiolucent implants such as the minimally invasive Photodynamic Bone Stabilization System (PBSS; IlluminOss Medical Inc), featuring a light cured polymer contained within an inflatable balloon catheter. Two participating hospitals in one health care system reviewed cases using the PBSS implant. Twenty-five patients with 29 impending or pathologic fractures in the proximal radius or humerus from metastatic carcinoma, myeloma, lymphoma, and melanoma were identified. Clinical charts and imaging were reviewed to determine the status of the implant at final follow-up as well as complications. For analysis, a chi-square test was used for nominal variables and a t test was used for continuous variables. Eleven of the 25 patients were alive with disease at the time of analysis. Eight of 29 (27.5%) implants failed. Five of 25 (20%) patients required repeat surgery due to complications, including 3 revision open reduction and internal fixations, 1 open reduction and internal fixation for a periprosthetic fracture, and 1 screw removal. Five of the 9 cases (56%) ( P =.03) with lesions in the distal humeral shaft had breakage of the implant by final follow-up, compared with 3 of 20 cases (15%) ( P =.03) elsewhere in the humerus; no failures were seen in the radius. One of 4 patients (25%) also had failure in the surgical neck, although this did not reach significance. Five patients were noted to have progression of disease on follow-up radiographs, with 4 failures in patients with progression. The PBSS implants potentially allow improved surveillance of fracture healing and tumor recurrence along with decreased scattering of radiation during treatment. Unfortunately, there may be a higher rate of mechanical failures, particularly for lesions involving the distal humerus. This may be due to decreased cross-sectional area of the implant in this region as compared with the metaphyseal and proximal regions. Caution should be exercised when treating distal humeral pathologic fractures with large lytic lesions where the underlying disease process is not well controlled. [ Orthopedics . 2021;44(3):154-159.].

Study Design: This was a subanalysis of an international, multicenter, open-label study., Objective: The aim of this study was to assess the efficacy and safety of denosumab in a subset of patients with giant cell tumors of bone (GCTB) of the spine including the sacrum from an international, open-label, single-arm, phase 2 study (ClinicalTrials.gov: NCT00680992)., Summary of Background Data: Standard GCTB treatment is surgical removal, either by curettage or resection, combined with intraoperative adjuvant therapy; however, some sites may not be amenable to resection (e.g., skull, spine)., Methods: Adults or skeletally mature adolescents with pathologically confirmed GCTB of the spine including the sacrum, and radiologically measurable evidence of active disease, were included. Patients received denosumab (120 mg subcutaneously) once every 4 weeks during the treatment phase, with loading doses on days 8 and 15 of the first cycle. Patients had surgically unsalvageable GCTB (Cohort 1), had planned surgery expected to result in severe morbidity (Cohort 2), or were enrolled from a previous GCTB study (Cohort 3)., Results: Overall, 132 patients were included in the safety analysis (103 in Cohort 1, 24 in Cohort 2, and five in Cohort 3); 131 patients were included in the efficacy analysis. Kaplan-Meier estimated probabilities of disease progression or recurrence were 3% (95% confidence interval [CI], 0.0-6.2) at year 1 and 7.4% (95% CI, 2.1-12.7) at years 3 and 5 in Cohort 1, and not estimable in Cohorts 2 and 3. Of 23 patients (Cohort 2) with surgery planned at baseline, 10 (43%) had on-study surgery; of these, one patient had reported disease progression or recurrence after the on-study surgery. Clinical benefit was reported in 83% of patients overall (all cohorts)., Conclusion: Results from the analysis suggest that denosumab is potentially effective treatment for patients with GCTB of the spine including the sacrum. The adverse event profile was consistent with the full study population.Level of Evidence: 2., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To review the evaluation, diagnosis, and treatment of spindle cell lipoma (SCL) with emphasis on the location of these tumours and the spectrum of magnetic resonance imaging (MRI) and computed tomography (CT) appearances., Materials and Methods: The MRI and CT findings of 27 histopathologically proven SCLs were evaluated retrospectively. Imaging features evaluated included margins, percentage visible fat, MRI signal characteristics, oedema, and contrast enhancement patterns., Results: Patient ages ranged from 18 to 80 years with an average age of 56.5 years. Men were affected twice as frequently as women (M=18, F=9). SCLs ranged in size from 2 to 10 cm, with an average greatest dimension of 5.5 cm. Five lesions (19%) contained no visible fat on CT or MRI, and the leading differential diagnosis of high-grade soft-tissue sarcoma diagnosis was suggested by referring surgeons. Five lesions (19%) had <50% fatty areas, nine lesions (52%) demonstrated >50% but <90% fat at MRI or CT. Only three of 25 lesions (12%) had an appearance of a typical lipoma on unenhanced MRI sequences. All SCLs that were imaged with contrast medium (n = 18) demonstrated some degree of enhancement, with eight (44%) showing marked enhancement, four (22%) showing moderate, and six (33%) minimal enhancement., Conclusion: SCLs have considerably variable imaging appearances and may have minimal or no visible fat at MRI or CT. Imaging features may make it difficult to distinguish this benign tumour from a potentially higher-grade malignant tumour., (Copyright © 2019 The Royal College of Radiologists. All rights reserved.)

Background: Giant-cell tumour of bone (GCTB) is a rare, locally aggressive osteoclastogenic stromal tumour of the bone. This phase 2 study aimed to assess the safety and activity of denosumab in patients with surgically salvageable or unsalvageable GCTB., Methods: In this multicentre, open-label, phase 2 study done at 30 sites in 12 countries we enrolled adults and skeletally mature adolescents (aged ≥12 years) weighing at least 45 kg with histologically confirmed and radiographically measurable GCTB, Karnofsky performance status 50% or higher (Eastern Cooperative Oncology Group status 0, 1, or 2), and measurable active disease within 1 year of study enrolment. Patients had surgically unsalvageable GCTB (cohort 1), had surgically salvageable GCTB with planned surgery expected to result in severe morbidity (cohort 2), or were enrolled from a previous study of denosumab for GCTB (cohort 3). Patients received 120 mg subcutaneous denosumab once every 4 weeks during the treatment phase, with loading doses (120 mg subcutaneously) administered on study days 8 and 15 to patients in cohorts 1 and 2 (patients in cohort 3 did not receive loading doses). The primary endpoint was safety in terms of the type, frequency, and severity of adverse events; secondary endpoints included time to disease progression from cohort 1 and the proportion of patients without surgery at month 6 for cohort 2. The safety analysis set included all enrolled patients who received at least one dose of denosumab. This study is registered with ClinicalTrials.gov, number NCT00680992, and has been completed., Findings: Between Sept 9, 2008, and Feb 25, 2016, 532 patients were enrolled: 267 in cohort 1, 253 in cohort 2, and 12 in cohort 3. At data cutoff on Feb 24, 2017, median follow-up was 58·1 months (IQR 34·0-74·4) in the overall patient population, and 65·8 months (40·9-82·4) in cohort 1, 53·4 months (28·2-64·1) in cohort 2, and 76·4 months (61·2-76·5) in cohort 3. During the treatment phase, the most common grade 3 or worse adverse events were hypophosphataemia (24 [5%] of 526 patients), osteonecrosis of the jaw (17 [3%], pain in extremity (12 [2%]), and anaemia (11 [2%]). Serious adverse events were reported in 138 (26%) of 526 patients; the most common were osteonecrosis of the jaw (17 [3%]), anaemia (6 [1%]), bone giant cell tumour (6 [1%]), and back pain (5 [1%]). 28 (5%) patients had positively adjudicated osteonecrosis of the jaw, four (1%) had atypical femur fracture, and four (1%) had hypercalcaemia occurring 30 days after denosumab discontinuation. There were four cases (1%) of sarcomatous transformation, consistent with historical data. Ten (2%) treatment-emergent deaths occurred (two of which were considered treatment-related; bone sarcoma in cohort 2 and sarcoma in cohort 1). Median time to progression or recurrence for patients in cohort 1 during the first treatment phase was not reached (28 [11%] of 262 patients had progression or recurrence). 227 (92%; 95% CI 87-95) of 248 patients who received at least one dose of denosumab in cohort 2 had no surgery in the first 6 months of the study., Interpretation: The types and frequencies of adverse events were consistent with the known safety profile of denosumab, which showed long-term disease control for patients with GCTB with unresectable and resectable tumours. Our results suggest that the overall risk to benefit ratio for denosumab treatment in patients with GCTB remains favourable., Funding: Amgen., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this paper is to describe the structure and impact of a Queensland Research Support Network (RSN) in emergency medicine (EM)., Design/methodology/approach: This paper presents a descriptive summary of EM networks, network evaluations and the structure and development of the Emergency Medicine Foundation's (EMF) RSN in Queensland, including an observational pre- and post-study of research metrics., Findings: In two years, the RSN supported 33 Queensland emergency departments (EDs), of which 14 developed research strategies. There was an increase in research active clinicians, from 23 in 2015 to 181 in 2017. Collaborator engagement increased from 9 in 2015 to 276 in 2017 as did the number of research presentations, from 6 in 2015 to 61 in 2017. EMF experienced a growth in new researchers, with new investigators submitting approximately 60 per cent of grant applications in 2016 and 2017. EMF also received new applications from a further three HHS (taking EMF-funded research activity from 8 to 11 HHS)., Research Limitations/implications: This paper describes changes in KPIs and research metrics, which the authors attribute to the establishment of the RSN. However, it is possible that attribution bias plays a role in the KPI improvements., Social Implications: This network has actively boosted and expanded EM research capacity and capability in Queensland. It provides services, in the form of on-the-ground managers, to develop novice clinician-researchers, new projects and engage entire EDs. This model may be replicated nationwide but requires funding commitment., Originality/value: The RSN improves front-line clinician research capacity and capability and increases research activity and collaborations with clear community outcomes. Collaborations were extended to community, primary health networks, non-government organisations, national and international researchers and academic institutions. Evaluating and measuring a network's benefits are difficult, but it is likely that evaluations will help networks obtain funding.

Background: Denosumab has been shown to reduce tumor size and progression, reform mineralized bone, and increase intralesional bone density in patients with giant cell tumor of bone (GCTB); however, radiologic assessment of tumors in bone is challenging. The study objective was to assess tumor response to denosumab using three different imaging parameters in a prespecified analysis in patients with GCTB from two phase 2 studies., Methods: The studies enrolled adults and adolescents (skeletally mature and at least 12 years of age) with radiographically measurable GCTB that were given denosumab 120 mg every 4 weeks, with additional doses on days 8 and 15 of cycle 1. The proportion of patients with an objective tumor response was assessed using either Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST), European Organisation for Research and Treatment of Cancer response criteria (positron emission tomography [PET] scan criteria), or inverse Choi density/size (ICDS) criteria. Target lesions were measured by computed tomography or magnetic resonance imaging (both studies), PET (study 2 only), or plain film radiograph (study 2 only)., Results: Most patients (71.6%) had an objective tumor response by at least one response criteria. Per RECIST, 25.1% of patients had a response; per PET scan criteria, 96.2% had a response; per ICDS, 76.1% had a response. 68.5% had an objective tumor response ≥ 24 weeks. Using any criteria, crude incidence of response ranged from 56% (vertebrae/skull) to 91% (lung/soft tissue), and 98.2% had tumor control ≥ 24 weeks. Reduced PET avidity appeared to be an early sign of response to denosumab treatment., Conclusion: Modified PET scan criteria and ICDS criteria indicate that most patients show responses and higher benefit rates than modified RECIST, and therefore may be useful for early assessment of response to denosumab., Trial Registration: ClinicalTrials.gov Clinical Trials Registry NCT00396279 (retrospectively registered November 6, 2006) and NCT00680992 (retrospectively registered May 20, 2008).

Objective: Drug trend data can inform appropriate policies to minimise drug-related harm, as well as assist in early detection and prevention. While Australia has a number of monitoring systems, none operate in regional areas. The aim of this study was to explore how drug trend and other data are used by the regional alcohol and other drug workforce., Method: Twenty-one key experts from regional Queensland were interviewed between November 2014 and August 2015. Key experts worked in or had contact with the broader alcohol and other drugs field in the Darling Downs area of Queensland. Interviews were analysed thematically., Setting: Darling Downs, Queensland., Results: Two themes emerged from the analysis. There were differences in workforce needs, with those in the law and criminal justice areas believing they had access to good, current data. Those in the health sector differed, although the majority indicated that there did appear to be a knowledge gap related to their location in a regional area., Conclusions: Trends in the use of, and harms related to, substance use are well captured in urban areas, but less so in regional areas. This inhibits both our understanding of where substance use is changing, as well as how to best plan and respond., (© 2017 National Rural Health Alliance Inc.)

Introduction and Aim: To understand health service access and needs of people who use performance and image enhancing drugs (PIED) in regional Queensland., Design and Methods: Semi-structured interviews were conducted with 21 people (n = 19 men) who reported the use of a range of PIEDs, including anabolic-androgenic steroids, human chorionic gonadotropin, growth hormone, clenbuterol, tamoxifen, insulin and peptides., Results: Participants reported accessing a range of services, including needle and syringe programs and pharmacies, for sterile injecting equipment. While PIEDs users attributed some stigma to needle and syringe programs, they were seen as an important service for injecting equipment. Participants reported receiving either positive care from health-care providers, such as general practitioners (GP), or having negative experiences due to the stigma attached with PIED use. Few participants reported disclosing their PIED use to their GP not only because of the concerns that their GP would no longer see them but also because they felt their GP was not knowledgeable about these substances., Discussion and Conclusion: Participants in the study reported no difficulty in accessing health services based on living in a regional area, with their concern focused more upon how they were viewed and treated by service staff. [Dunn M, Henshaw R, Mckay F. H. Do performance and image enhancing drug users in regional Queensland experience difficulty accessing health services? Drug Alcohol Rev 2016;35:377-382]., (© 2015 Australasian Professional Society on Alcohol and other Drugs.)

Vancomycin is a glycopeptide antibiotic that exhibits bactericidal activity against gram-positive cocci. It is commonly recommended for surgical prophylaxis in cases of suspected bacterial resistance or penicillin allergy. There are 2 main types of hypersensitivity reactions associated with vancomycin. Red man syndrome is an anaphylactoid reaction caused by direct release of histamine. The second is an anaphylactic reaction, which is an immunoglobulin E-mediated response. We present the case of a 55-year-old woman with a history of metastatic giant cell tumor of the right proximal tibia. She had undergone multiple surgeries for this and other nonorthopedic conditions. The patient received vancomycin for the majority of these procedures and extended courses of vancomycin on 2 separate occasions. In the present case, the patient was taken to the operating room for a prosthetic infection, and vancomycin was given after cultures were taken. The patient immediately developed signs consistent with anaphylaxis and disseminated intravascular coagulation. This was treated acutely with hemodynamic resuscitation, replacement of blood components, steroids, and repeated boluses of epinephrine. She recovered and was taken back to the operating room during that same admission without incident. The patient has since been treated with systemic daptomycin and a tobramycin cement spacer without further incident.

Background: Giant cell tumour of bone (GCTB) is a very rare, aggressive, and progressive osteolytic tumour for which no standard medicinal treatment or chemotherapy exists. We report interim safety and efficacy results from a phase 2 study of denosumab in patients with GCTB., Methods: We did an international, open-label, parallel-group, phase 2 trial of patients with histologically confirmed GCTB and radiographically measurable active disease. Eligible patients were adults or skeletally mature adolescents with radiographic evidence of at least one mature long bone who were at least 12 years old and weighed at least 45 kg. We divided patients into three cohorts--those with surgically unsalvageable GCTB (cohort 1), those with salvageable GCTB whose surgery was associated with severe morbidity (cohort 2), and those who transferred from a previous study of denosumab for GCTB (cohort 3). Patients in cohorts 1 and 2 received 120 mg of subcutaneous denosumab every 4 weeks with loading doses on days 8 and 15 of the first cycle; those in cohort 3 continued the regimen from the previous study. Investigator-determined disease status and clinical benefit were assessed every 4 weeks. Our primary endpoint was the safety profile of denosumab in terms of adverse events and laboratory abnormalities. Prespecified secondary endpoints were time to disease progression in cohort 1 and the proportion of patients without any surgery at 6 months in cohort 2. Safety analyses included all patients who received at least one dose of denosumab. Efficacy analyses included all eligible patients who received at least one dose of denosumab. This study is registered with ClinicalTrials.gov, identifier NCT00680992., Findings: 282 patients, including ten adolescents, were included between Sept 9, 2008, and March 25, 2011. Of the 281 patients analysable for safety, three (1%) had osteonecrosis of the jaw and 15 (5%) hypocalcaemia. The most common grade 3-4 adverse events were hypophosphataemia, which occurred in nine (3%) patients, and anaemia, back pain, and pain in extremities, each of which occurred in three patients (1%). Serious adverse events were reported in 25 (9%) patients. No treatment-related deaths were reported. On the basis of investigators' assessment of disease status, 163 of 169 (96%) analysable patients in cohort 1 had no disease progression after median follow-up of 13 months (IQR 5·8-21·0). In cohort 2, 74 of 100 (74%) analysable patients had no surgery and 16 of 26 (62%) patients who had surgery underwent a less morbid procedure than planned. Median follow-up in cohort 2 was 9·2 months (IQR 4·2-12·9)., Interpretation: Adverse events were consistent with the known safety profile of denosumab. Denosumab was associated with tumour responses and reduced the need for morbid surgery in patients with GCTB. Denosumab represents a new treatment option for patients with GCTB., Funding: Amgen., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Soft tissue mesenchymoma is an exceptionally rare and benign neoplasm. Since its initial description in 1962, only 7 cases of cartilage predominant appendicular mesenchymoma have been reported. Of these, only 2 patients were skeletally immature. We report the clinical, pathologic, and radiologic features of a 13-year-old adolescent boy with a benign mesenchymoma in the distal leg.

Background: The increasing prevalence of obesity in women of child-bearing age is of growing concern in the health community. Obesity is associated with sub-optimal reproductive performance; therefore, it is understandable that the number of young women with elevated body mass index (BMI) accessing assisted reproductive treatment (ART) is on the rise. Consequently, this study not only assessed the impact of BMI on fertilisation rates, embryo development and freezing during ART in women aged ≤38 years but also determined their subsequent pregnancy and delivery rates., Methods: Data were retrospectively analysed from all cycles initiated in 2006/2007 for women aged ≤38 years. The BMI categorisations were as follows: normal - 18.5-24.9 kg/m(2) ; overweight - 25-29.9 kg/m(2) ; obese - 30-34.9 kg/m(2) ; morbidly obese class I - 35-39.9 kg/m(2) ; morbidly obese class П -≥40 kg/m(2) ., Results: Obese and morbidly obese women required a significantly higher follicle stimulating hormone start dose than normal BMI women; however, they obtained significantly fewer oocytes (P < 0.05). Although BMI did not affect embryo development, morbidly obese class Π women had significantly reduced pregnancy rates compared to normal BMI women (30.5 vs 41.7%, respectively; P < 0.05). Furthermore, increasing BMI was positively correlated to increasing rates of preterm delivery (P < 0.05). Increasing BMI was also positively correlated to increasing delivery rates of singleton term macrosomic offspring (≥4000 g)., Conclusion: Obesity in women aged≤38 years does not affect embryo development; however, it does reduce clinical pregnancy rates in women with a BMI≥40 and increases rates of preterm labour and delivery of macrosomic offspring., (© 2012 The Authors ANZJOG © 2012 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: While complications following massive endoprosthetic reconstruction have been previously described, the incidence and effects of these complications over extended periods of time have not been well characterized in large series., Questions/purposes: We therefore determined: (1) incidence and types of complications; (2) relative risk of complications; (3) likelihood of secondary complications; (4) whether modularity altered such complications; (5) implant failure and limb salvage rates and (6) implant survival over extended followup., Methods: We retrospectively reviewed 232 patients (241 implants: 50 custom,191 modular) who underwent endoprosthetic reconstruction for malignant and aggressive bone tumors between 1980 and 2002. Complications were classified as infection, mechanical, superficial soft tissue, deep soft tissue, or dislocation. Survival was determined by Kaplan-Meier analysis. Minimum followup was 5 years (mean: 10 years; range: 5-27 years)., Results: One hundred thirty-seven of 232 patients (59%) underwent a single reconstruction. Ninety-five patients had 242 additional procedures. Forty-four revised patients retained their original prosthesis. Limb salvage rate was 90%; implant failure (removal of the cemented part) was seen in 29% (70/241) with a median survival of 190 months. Twenty-five of 50 custom implants failed (8 then failed again) while 30/180 modular implants failed (7 then failed again). Of 70 instances of implant failure, 38/70 were mechanical, 27/70 infectious. Risk of infection increased 30% after a second procedure; 16 of 24 amputations were performed because of infection., Conclusions: Mechanical complications were the most common cause of implant failure. Infection was the leading cause of both complication and amputation; risk of infection increased substantially with revision surgery. Modular implants had fewer mechanical complications, thus leading to fewer revisions and subsequent infections.

Background: Giant-cell tumour (GCT) of bone is a primary osteolytic bone tumour with low metastatic potential and is associated with substantial skeletal morbidity. GCT is rich in osteoclast-like giant cells and contains mononuclear (stromal) cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. We investigated the potential therapeutic effect of denosumab, a fully human monoclonal antibody against RANKL, on tumour-cell survival and growth in patients with GCT., Methods: In this open-label, single-group study, 37 patients with recurrent or unresectable GCT were enrolled and received subcutaneous denosumab 120 mg monthly (every 28 days), with loading doses on days 8 and 15 of month 1. The primary endpoint was tumour response, defined as elimination of at least 90% of giant cells or no radiological progression of the target lesion up to week 25. Study recruitment is closed; patient treatment and follow-up are ongoing. The study is registered with Clinical Trials.gov, NCT00396279., Findings: Two patients had insufficient histology or radiology data for efficacy assessment. 30 of 35 (86%; 95% CI 70-95) of evaluable patients had a tumour response: 20 of 20 assessed by histology and 10 of 15 assessed by radiology. Adverse events were reported in 33 of 37 patients; the most common being pain in an extremity (n=7), back pain (n=4), and headache (n=4). Five patients had grade 3-5 adverse events, only one of which (grade 3 increase in human chorionic gonadotropin concentration not related to pregnancy) was deemed to be possibly treatment related. Five serious adverse events were reported although none were deemed treatment related., Interpretation: Further investigation of denosumab as a therapy for GCT is warranted., Funding: Amgen, Inc., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: The inconsistency in healing after anterior cruciate ligament (ACL) repair has been attributed to ACL fibroblast cellular metabolism, lack of a sufficient vascular supply, and the inability to form a scar or scaffold after ligament rupture because of the uniqueness of the intra-articular environment. Hypotheses (1) Stress deprivation in the surgically transected ACL will increase matrix metalloproteinase (MMP) and alpha smooth muscle actin (alpha-SMA) expression. (2) Stress deprivation will decrease collagen expression. (3) The transected anteromedial bundle of the ACL will demonstrate a pattern of gene expression similar to the completely transected ACL, while gene expression profiles in the intact posterolateral bundle will be similar to the sham-operated controls., Study Design: Controlled laboratory study., Methods: Thirty-six New Zealand White rabbits underwent a partial ACL surgical transection separating the anteromedial (AM) and posterolateral (PL) bundles and transecting the AM bundle. Contralateral ACLs were either sham operated or completely transected. Ligament tissue was harvested at 1, 2, or 6 weeks after surgery, and real-time PCR was performed using primers for collagen I, collagen III, alpha-SMA, MMP-1, and MMP-13., Results: At 1 week, a 28- and 29-fold increase in MMP-13 expression was seen in the complete transection and the transected AM bundle specimens when compared with sham-operated controls (P = .049, P = .018), respectively. There was no significant difference in MMP-13 between the sham controls and the intact PL bundle specimens. A 22- and 23-fold increase in alpha-SMA was seen (P = .03, P = .009) in the complete transection and transected AM bundle specimens, respectively, while no difference was seen between the intact PL bundle and controls. No significant differences were seen in collagen I (Col I) or collagen III (Col III) gene expression at 1 week. At 6 weeks, Col I expression increased 5-fold in complete transection samples (P = 3.9 x 10(-6)), 3-fold in transected AM samples (P = 3.3 x 10(-6)), and 2-fold in the intact PL bundle samples as compared with controls. alpha-SMA was increased 7.5-fold and 5-fold in complete transection and transected AM samples, respectively (P = .004, P = 2.2 x 10(-6)), while no significant change was seen in the intact PL bundle samples compared with controls. Complete transection specimens showed a 3-fold increase in MMP-1 expression. Col III increased 5.4-, 2.6-, and 2.4-fold in the complete transection, transected AM, and intact PL groups, respectively (P = .003, P = .004, P = .04)., Conclusion: Partial or complete surgical transection of the rabbit ACL with resultant loss of mechanical stimuli results in an increase in MMP-13 and alpha-SMA expression at the early time point (1 week) and an increase in alpha-SMA, Col I, and Col III expression at the later time point (6 weeks). These data provide support for the hypothesis that there is a time-dependent alteration of anabolic and catabolic matrix gene expression after injury/loss of ligament integrity. Clinical Relevance Identification of pathways that respond to mechanical stress in the intact ACL and after surgical transection may permit development of novel therapies to alter healing of the partial ACL injury or to assist in the development of biomechanical active ''smart'' scaffolds for tissue-engineered ligament replacements.

The role of cell surface integrins in cell migration, proliferation, and attachment to matrix molecules is well known. Integrin-matrix interactions have been implicated in mechanotransduction and load transmission from the outside to the inside of the cell. In this study, the effect of cyclic strain on the cell proliferation, attachment, and expression of integrin subunits beta1, beta3, and alpha5 was determined in anterior cruciate ligament (ACL) and medial collateral ligament (MCL) fibroblasts grown on polystyrene, Type I collagen, laminin, elastin, and fibronectin. ACL fibroblast proliferation was not affected by growth substrate whereas MCL cells reached confluence more rapidly on fibronectin compared with collagen or polystyrene. Exposure to 5% cyclic strain resulted in a significant decrease in ACL and MCL fibroblast proliferation on fibronectin and Type I collagen. MCL cells showed a greater strain-dependent inhibition of cells grown on a fibronectin substrate than those grown on collagen. This matrix-dependent effect of strain on cell proliferation was not seen with ACL cells. Attachment of ACL and MCL fibroblasts was stronger to fibronectin compared with Type I collagen, laminin, and polystyrene. In the absence of applied load, the expression of beta1, beta3, and alpha5 subunits was not substrate dependent and the expression of beta1 and alpha5 integrin subunits was higher in MCL cells than ACL cells on all substrates. In contrast, the expression of beta3 integrin subunit was higher in ACL cells than MCL cells. In response to 5% strain, beta1, and alpha5 expression increased in all fibroblasts with MCL cells having a higher magnitude of expression. beta3 expression showed a 90% increase in response to load when grown on laminin for both MCL and ACL fibroblasts and demonstrated no change in expression on Type I collagen or fibronectin. The duration of applied strain from 2 versus 22 h had no effect on cell proliferation or integrin expression., ((c) 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.)

Objective: To compare microwave endometrial ablation (MEA) with a levonorgestrel-releasing intrauterine device (Mirena) in the management of heavy menstrual bleeding., Design: A retrospective cohort study, Sample: Thirty-nine women were treated with MEA and 23 women with Mirena, in the South East Regional Health Service of South Australia during 1998 to 2001; the mean duration of follow-up was 14.6 months., Main Outcome Measures: Primary measures included acceptability of the treatment process, effectiveness of the treatment, and satisfaction with outcomes. Secondary measures included side effects, complications and quality of life (using the SF-36)., Results: Acceptability of the treatment process and satisfaction with outcomes was very high for both procedures. Each treatment led to a statistically significant reduction in menstrual bleeding (p < 0.0001) and dysmenorrhoea scores (p < 0.002)., Conclusions: There were no statistical differences between the two treatments for any of the primary or secondary outcome measures assessed. The treatments seem equally effective in the management of heavy menstrual loss.

Background: Induction chemotherapy can produce dramatic necrosis in sarcomas-raising the question of whether or not radiation is necessary. This study reviews the clinical outcome of a subset of patients with high-grade extremity soft tissue sarcomas (STS) who were treated with induction chemotherapy and surgical resection but without radiation., Methods: Nonmetastatic, large, high-grade STS of the pelvis and extremities were treated with intra-arterial cisplatin, adriamycin, and, after 1995, ifosfamide. After induction, oncologic resection and histologic evaluation were performed. Good responders with good surgical margins were not treated with radiation., Results: Thirty-three patients, with a median follow-up of 5 years, were included. Limb salvage rate was 94%. Median tumor necrosis was 95%. Four patients developed metastatic disease with three subsequent deaths. Two local recurrences occurred; both patients were salvaged with reresection and adjuvant external beam radiotherapy, although one died of metastatic disease 10 years later. Relapse-free and overall survival is 80% and 88% at 5 and 10 years by Kaplan-Meier analysis., Conclusions: Intensive induction chemotherapy can be extremely effective for high-grade STS, permitting limb-sparing surgery in lieu of amputation. Radiation may not be necessary if a good response to induction chemotherapy and negative wide margins are achieved. All patients with large, deep, high-grade STS of the extremities should be considered candidates for induction chemotherapy.

Dislocation is the most common complication after proximal and total femur endoprosthetic reconstruction. The current study describes a surgical technique of acetabular preservation and reconstruction of the joint capsule and abductor mechanism that recreates joint stability and avoids dislocation. Between 1980 and 1996, 57 patients underwent proximal or total femur resection with endoprosthetic reconstruction. Forty-six patients had primary sarcoma of bone, nine had other bone tumors, and two had metabolic bone disease. The acetabulum was spared and not resurfaced in all patients. Bipolar hemiarthroplasty was performed in 49 patients, and fixed unipolar hemiarthroplasty was performed in eight. Soft tissue reconstruction included Dacron tape capsulorrhaphy over the prosthetic neck, reattachment of the abductor mechanism to the prosthesis, and extracortical bone fixation. The average followup period was 6.5 years (range, 2-18.2 years). Dislocation occurred in only one (1.7%) patient, and aseptic prosthetic loosening occurred in three (5.3%) patients. Four patients with primary bone sarcoma had local recurrence, of whom one required amputation of the limb. The limb salvage rate was 98%. Eighty-one percent of the patients had a good to excellent functional outcome. Acetabular preservation, capsulorrhaphy, and reconstruction of the abductor mechanism recreate hip stability and avoid dislocation after proximal and total femur endoprosthetic reconstruction.

Study Design: Between 1982 and 1997, the authors treated 32 patients with sciatica who subsequently were found to have a tumor along the extraspinal course of the sciatic nerve., Summary of Background Data: Extraspinal compression of the sciatic nerve by a tumor is a rare cause of sciatica. Signs and symptoms overlap those of the more common causes of sciatica (i.e., herniated disc and spinal stenosis)., Objective: To characterize the unique clinical presentation of these patients and to formulate guidelines that may lead to early diagnosis., Methods: All pertinent clinical data and studies were reviewed retrospectively, and standard demographic data were collected for analysis., Results: These patients typically sought treatment for an insidious onset of sciatic pain that was constant, progressive, and unresponsive to change in position or bed rest. The mean time to final diagnosis was 11.9 months (median, 6 months). Seventeen patients were able to locate their pain to a specific point along the extraspinal course of the sciatic pain, and a mass was noted in 13 patients. Eighteen of these tumors were in the pelvis, 10 in the thigh, and 4 in the popliteal fossa and calf., Conclusions: A high index of clinical suspicion is the key to early diagnosis of bone or soft-tissue tumors as a cause of sciatica; special attention should be given to pain pattern, physical examination of the entire course of the sciatic nerve, and selection of proper imaging studies. Routine anteroposterior plain radiography of the pelvis as part of the initial imaging screening process is recommended.

Between 1983 and 1993, 102 patients with giant cell tumor of bone were treated at three institutions. Sixteen patients (15.9%) presented with already having had local recurrence. All patients were treated with thorough curettage of the tumor, burr drilling of the tumor inner walls, and cryotherapy by direct pour technique using liquid nitrogen. The average followup was 6.5 years (range, 4-15 years). The rate of local recurrence in the 86 patients treated primarily with cryosurgery was 2.3% (two patients), and the overall recurrence rate was 7.9% (eight patients). Six of these patients were cured by cryosurgery and two underwent resection. Overall, 100 of 102 patients were cured with cryosurgery. Complications associated with cryosurgery included six (5.9%) pathologic fractures, three (2.9%) cases of partial skin necrosis, and two (1.9%) significant degenerative changes. Overall function was good to excellent in 94 patients (92.2%), moderate in seven patients (6.9%), and poor in one patient (0.9%). Cryosurgery has the advantages of joint preservation, excellent functional outcome, and low recurrence rate when compared with other joint preservation procedures. For these reasons, it is recommended as an adjuvant to curettage for most giant cell tumors of bone.

Objective: To describe and compare health outcomes two years after medical abortion or vacuum aspiration in women recruited into a patient preference trial during 1990 to 1991., Design: Women recruited to the original, partially randomised study were contacted for assessment using a structured interview., Setting: Grampian region of Scotland, UK., Participants: One hundred and forty women who had participated in a partially randomised study of first trimester abortion two years previously., Intervention: Vacuum aspiration or medical abortion using mifepristone and gemeprost., Main Outcome Measures: Long-term general, reproductive and psychological health; acceptability of procedure; perceived value of choice of method of termination., Results: There were no significant differences between women who had undergone medical abortion or vacuum aspiration two years previously in general, reproductive or psychological health. Almost all women placed a high value on the provision of choice of method of termination. There was a significant difference in perception of long term procedure acceptability among women who had been randomised to a method of termination., Conclusions: Women should have the opportunity to choose the method of termination. This opportunity will result in high levels of acceptability, particularly at gestations under 50 days of amenorrhoea.

Objectives: To estimate and compare the costs of surgical and medical treatment of miscarriage to the National Health Service., Design: A patient-centred, partially randomised trial., Setting: A teaching hospital in Scotland., Participants: Four hundred and thirty-seven women with a proven first trimester miscarriage., Main Outcome Measures: The cost per patient of surgical and medical management of miscarriage plus the extra cost per patient of introducing medical management of miscarriage under three different scenarios are calculated., Results: The average cost of surgical treatment was Pounds 397 compared with Pounds 347 for medical treatment. Sensitivity analysis showed that the extra cost of introducing the medical management of miscarriage ranged from a cost saving of Pounds 71 per patient to an additional cost of Pounds 47 per patient., Conclusions: Our analysis showed that it may be possible to generate cost savings by introducing medical methods in the management of early miscarriage. However, the savings assume that costs associated with theatre use can be fully realised.

Knee dislocation after high energy trauma poses a major challenge to patients and treating physicians. The case presented documents the history and treatment of an unreduced posterior knee dislocation discovered 24 weeks after injury. Delayed surgical reduction was achieved, and satisfactory results were obtained with 22 months of followup of the patient. A detailed review of the literature found no comparable examples of longstanding traumatic dislocations of the knee but shed light on the probable cause for this unusual case. Close clinical followup, even after appropriate initial treatment of knee dislocations, is needed to eliminate similar occurrences.

The mitochondrial toxin 3-nitropropionic acid (3-NP) produces selective striatal lesions in both experimental animals and humans. The pathogenesis of the lesions involves secondary excitotoxicity that may then lead to free radical generation. To test this further we examined the effects of 3-NP in both transgenic (Tg) mice that carry the complete sequence for the human copper/zinc superoxide dismutase (SOD) gene as well as non-Tg littermate controls. The Tg-SOD mice showed a pronounced attenuation of Nissl-stained striatal lesions compared with non-Tg mice. Systemic administration of 3-NP resulted in production of hydroxyl free radicals as assessed by the conversion of salicylate to 2,3- and 2,5-dihydroxybenzoic acid. This production was attenuated significantly in Tg-SOD mice. In a similar way, 3-NP produced significant increases in 3-nitrotyrosine/tyrosine, a marker for peroxynitrite-mediated damage, which were significantly attenuated in Tg-SOD mice. These results support that oxygen free radicals and peroxynitrite play an important role in the pathogenesis of 3-NP neurotoxicity.

Basic fibroblast growth factor (bFGF) is a polypeptide growth factor that promotes neuronal survival. We recently found that systemic administration of bFGF protects against both excitotoxicity and hypoxia-ischemia in neonatal animals. In the present study, we examined whether systemically administered bFGF could prevent neuronal death induced by intrastriatal injection of N-methyl-D-aspartate (NMDA) or chemical hypoxia induced by intrastriatal injection of malonate in adult rats and 1-methyl-4-phenylpyridinium (MPP+) in neonatal rats. Systemic administration of bFGF (100 micrograms/kg) for three doses both before and after intrastriatal injection of either NMDA or malonate in adult rats produced a significant neuroprotective effect. In neonatal rats, bFGF produced dose-dependent significant neuroprotective effects against MPP+ neurotoxicity, with a maximal protection of approximately 50% seen with either a single dose of bFGF of 300 micrograms/kg or three doses of 100 micrograms/kg. These results show that systemic administration of bFGF is effective in preventing neuronal injury under circumstances in which the blood-brain barrier may be compromised, raising the possibility that this strategy could be effective in stroke.

Background: A substantial body of objective data now exists to support the consensus view that induced abortion results in a low incidence of psychiatric morbidity. However, these data do not include more recent advances in abortion technology. Medical abortion entails a participatory role on the part of the woman, who may perceive more pain or see products of conception. The physical and psychological events experienced by women undergoing this procedure may lead to differences in psychopathology., Methods: 363 women undergoing legal induced abortion up to 63 days gestation were allocated by a prospective partially randomised design to undergo medical abortion (using mifepristone 600 mg followed 48 h later by gemeprost 1 mg vaginal pessary) or vacuum aspiration performed under general anesthesia. This study design allowed women with a preference for a particular method to undergo that method; women without preferences were allocated at random. Women completed sensitive and reliable psychometric instruments (the Hospital Anxiety and Depression Scale and a semantic differential rating scale designed to measure self-esteem) prior to abortion and 16 days later., Results: There were no significant differences between women allocated at random to medical abortion or vacuum aspiration in post-abortal anxiety, depression or low self-esteem. Women with high levels of mood disturbance prior to abortion, who were smokers or who had medical complications following abortion were at highest risk of post-abortal mood disorder., Conclusions: Medical abortion is a psychologically safe as surgical vacuum aspiration. The quantitative findings of the study support the consensus view that abortion is associated with high incidence of psychological benefit, whichever method is used.

To determine whether the strain patterns produced in the femoral cortex after uncemented femoral arthroplasty are influenced by the fit of the component and whether these patterns are different from those of cemented components, cortical surface strains of cadaveric femurs subjected to loads simulating single-limb stance were measured before and after the insertion of uncemented, collared, straight-stemmed femoral components. The effects of press fit, loose fit, and precise fit of the components were evaluated and were contrasted to the strain patterns occurring after insertion of cemented femoral components. Strains varied markedly, depending on the fit of the stem of the uncemented femoral component within the isthmus. Nearly normal patterns of femoral strain were produced when the femoral stem was fit precisely at the isthmus, and the proximal femoral strains were similar to those of the intact state. In contrast, press fit and loose fit at the isthmus altered the strain patterns. The proximal medial axial strains were significantly reduced with press fit, to a mean of 39% of normal (p < 0.05), and increased with loose fit, to a mean of 141% of normal (p < 0.05). The prostheses fixed with cement showed a mean reduction in proximal medial axial strains to 33% of normal, which was comparable with press fit uncemented components even though the collar was well seated. Thus, our findings indicated that, in the immediate postoperative period, femoral strain patterns can be influenced by the fit of an uncemented component within the isthmus and by the use of cement.

The assembly strains produced in cadaver femurs during uncemented femoral arthroplasty were measured using strain gages and photoelastic coatings. Resecting the femoral neck, reaming the canal with power drills, and rasping with an optimal size rasp, as determined by preoperative radiographic templating, produced small assembly strains, up to 300 microstrain. Insertion of an optimal-size prosthesis after preparing the femoral canal with instruments the same size as the prosthesis produced moderate assembly strains, up to 1,000 microstrain. Half a millimeter press-fit of optimal prostheses produced larger assembly strains, up to 2,000 microstrain. Half a millimeter press-fit of a prosthesis that was also one size (1.0 mm) larger than that determined to be optimum produced even larger assembly strains (2,000-6,000 microstrain) and longitudinal linear fractures in the femoral cortex. Insertion of prostheses that were smaller than the rasps produced minimal strains in the femoral cortex. The magnitude of peak strains produced by press-fitting the femoral components and the small amounts of disparity between the size of the recess and the prosthesis necessary to produce these strains show the narrow range of tolerances available to the surgeon. Cementless femoral arthroplasty requires great care in preparing the femoral canal to the appropriate size as determined from preoperative templating, using accurate and precisely toleranced instrumentation and prosthetic components in order to avoid femoral fractures, yet obtain a stable fit.

Objectives: To assess women's preferences for, and the acceptability of, medical abortion and vacuum aspiration in the early first trimester., Design: Patient centred, partially randomised trial. Medical abortion was performed with mifepristone 600 mg followed 48 hours later by gemeprost 1 mg vaginal pessary. Vacuum aspiration was performed under general anaesthesia., Setting: Teaching hospital in Scotland., Patients: 363 women undergoing legal induced abortion at less than nine weeks' gestation., Main Outcome Measures: Women's preferences for method of abortion before abortion; acceptability judged two weeks after abortion by recording the method women would opt to undergo in future and by semantic differential rating technique., Results: 73 (20%) women preferred to undergo medical abortion, and 95 (26%) vacuum aspiration; 195 (54%) were willing to undergo either method, and were allocated at random. Both procedures were highly acceptable to women with preferences. Gestation had a definite effect on acceptability in randomised women; at less than 50 days there were no differences, but between 50 and 63 days vacuum aspiration was significantly more acceptable., Conclusions: Women who wish to use a particular method should be allowed their choice, regardless of gestation. Women of 50-63 days' gestation without preferences for a particular method are likely to find vacuum aspiration more acceptable. A patient centred, partially randomised trial design may be a useful tool in pragmatic research.

Intrastriatal injection of malonate, a reversible inhibitor of succinate dehydrogenase (SDH), produced age-dependent striatal lesions, which were significantly greater in 4- and 12-month-old animals than in 1-month-old animals. Both histologic and neurochemical studies showed that the lesions were significantly attenuated by administration of the noncompetitive NMDA receptor antagonist MK-801. Water-suppressed chemical shift magnetic resonance imaging showed that malonate produces increased striatal lactate concentrations and striatal lesions on T2-weighted scans that were attenuated by MK-801. Neurochemical characterization of the lesions showed significant decreases in markers of medium-sized spiny neurons (GABA and substance P), whereas a marker of medium-sized aspiny neurons (somatostatin) was not different from control values, consistent with an NMDA receptor-mediated mechanism. The effects of intrastriatal injections of malonate on ATP concentrations were compared with those of the irreversible SDH inhibitor 3-nitropropionic acid (3-NP). The ATP depletions following an equimolar injection of malonate were less marked and more transient than those of 3-NP. These results show that the competitive SDH inhibitor malonate produces more transient and milder bioenergetic defects than 3-NP, which are associated with selective activation of NMDA receptors. The results strengthen the possibility that a subtle impairment of energy metabolism may play a role in the pathogenesis of Huntington's disease.

Objective: To compare the effectiveness of 200 mg mifepristone with 1 mg gemeprost vaginal pessary in achieving cervical dilatation and softening ('priming') before late first trimester pregnancy vacuum aspiration., Design: A randomized, operator blind, placebo controlled trial., Setting: UK teaching hospital., Subjects: 90 primigravid women with 63-91 days amenorrhoea and ultrasonically confirmed single living fetus of correct size for gestational age., Interventions: The women were allocated to receive 200 mg mifepristone orally or an identical oral placebo 36 h before operation or 1 mg gemeprost vaginal pessary 3-4 h preoperatively., Main Outcome Measures: Onset of new symptoms following drug administration, a proven objective measure of the force required to dilate the cervix, and estimated intraoperative blood loss., Results: There were no significant differences in the baseline cervical dilatation, the force required to dilate the cervix or the volume of intraoperative blood loss between the active treatment groups. Both drugs were significantly more effective than placebo. Significantly fewer women in the mifepristone group had adverse side effects than in the gemeprost group., Conclusions: Mifepristone is a highly effective cervical priming agent, and has the advantages of being an oral preparation associated with few side effects.

Arctic foxes and gray wolves maintain their foot temperature just above the tissue freezing point (about -1 degrees C)when standing on extremely cold snow, or when the foot is immersed in a -35 degrees C bath in the laboratory. Proportional thermoregulation stabilized the subcutaneous temperature of the foot pad to a precision of +/- 0.7 degrees C (largest deviations). Selective shunting of blood-borne body heat through a cutaneous vascular plexus in the foot pad accounted for more than 99 percent of measured heat loss from the pad surface. Maximum energetic efficiency is achieved because the unit of heat exchange is located in the pad surface which contacts the cold substrate rather than throughout the pad.