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Introduction: An ongoing discussion is whether using a hydroxyapatite coating enhances the ingrowth and longevity of a femoral stem in total hip arthroplasty. The best way to predict speed of ingrowth and long-term outcome is by evaluating micromotion by radiostereometric analysis. To study the effect of hydroxyapatite (HA) coating on the migration of the SL-PLUS hip stem, we performed a prospective double blind randomised controlled trial comparing the early migration of the hydroxyapatite (HA)-coated SL-PLUS stem compared to the Standard (non-coated) SL-PLUS stem. Patients and methods: 51 patients were randomly assigned to receive either an uncoated or a HA-coated femoral component during total hip replacement. RSA images were obtained direct postoperatively and at 6 weeks, 12 weeks, 6 months, 12 months and 24 months. HOOS scores were obtained preoperative and at final follow-up. Results: RSA evaluation demonstrated significant migration up to 3 months postoperatively in both groups. After initial setting no significant migration was observed. There was no significant difference in migration between the HA-coated group and the uncoated group. Both Harris Hip Score (HHS) and HOOS domain scores (pain and ADL) significantly improved compared to baseline at 24 months after surgery in both treatment groups (pConclusions: At 2 years follow-up, the HA-coated and uncoated Zweymuller type, distal fitting stem do not show different migration patterns.

To evaluate the efficacy on physical functioning and safety of tailored exercise therapy in patients with knee osteoarthritis (OA) and comorbidities.In a randomized controlled trial, 126 participants were included with a clinical diagnosis of knee OA and at least 1 of the following target comorbidities: coronary disease, heart failure, type 2 diabetes mellitus, chronic obstructive pulmonary disease, or obesity (body mass index ≥30 kg/mStatistically significant physical functioning differences over time were found between the intervention and control group (WOMAC: B = -7.43 [95% confidence interval (95% CI) -9.99, -4.87], P 0.001; and 6MWT: B = 34.16 [95% CI 17.68, 50.64], P 0.001) in favor of the intervention group. At 3 months followup, the mean improvements in the intervention group were 33% on the WOMAC scale and 15% on the 6MWT. These improvements are of clinical relevance. No serious adverse events occurred during the intervention.This is the first study showing that tailored exercise therapy is efficacious in improving physical functioning and safe in patients with knee OA and severe comorbidities.

A multiplatform approach, including conventional cytogenetic techniques, BAC array comparative genomic hybridization, and Affymetrix 500K SNP arrays, was applied to the study of the tumor genomes of 25 follicular lymphoma biopsy samples with paired normal DNA samples to characterize balanced translocations, copy number imbalances, and copy-neutral loss of heterozygosity (cnLOH). In addition to the t(14;18), eight unique balanced translocations were found. Commonly reported FL-associated copy number regions were revealed including losses of 1p32-36, 6q, and 10q, and gains of 1q, 6p, 7, 12, 18, and X. The most frequent regions affected by copy-neutral loss of heterozygosity were 1p36.33 (28%), 6p21.3 (20%), 12q21.2-q24.33 (16%), and 16p13.3 (24%). We also identified by SNP analysis, 45 aberrant regions that each affected one gene, including CDKN2A, CDKN2B, FHIT, KIT, PEX14, and PTPRD, which were associated with canonical pathways involved in tumor development. This study illustrates the power of using complementary high-resolution platforms on paired tumor/normal specimens and computational analysis to provide potential insights into the significance of single-gene somatic aberrations in FL tumorigenesis.

We present the outcome of an independent prospective series of phase-3 Oxford medial mobile-bearing unicompartmental knee replacement surgery. Eight surgeons performed the 154 procedures in a community-based hospital between 1998 and 2003 for patients aged 60 and above. Seventeen knees were revised; in 14 cases a total knee replacement was performed, in 3 cases a component of the unicompartmental knee prosthesis was revised, resulting in a survival rate of 89% during these 2-7 years follow-up interval. This study shows that mobile-bearing unicompartmental knee replacement using a minimally invasive technique is a demanding procedure. The study emphasises the importance of routine in surgical management and strict adherence to indications and operation technique used to reduce outcome failure.

Item does not contain fulltext BACKGROUND: The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) has been extensively evaluated in groups of patients with osteoarthritis, yet not in patients with a femoral neck fracture. This study aimed to determine the reliability, construct validity, and responsiveness of the WOMAC compared with the Short Form-12 (SF-12) and the EuroQol 5D (EQ-5D) questionnaires for the assessment of elderly patients with a femoral neck fracture. METHODS: Reliability was tested by assessing the Cronbach alpha. Construct validity was determined with the Pearson correlation coefficient. Change scores were calculated from ten weeks to twelve months of follow-up. Standardized response means and floor and ceiling effects were determined. Analyses were performed to compare the results for patients less than eighty years old with those for patients eighty years of age or older. RESULTS: The mean WOMAC total score was 89 points before the fracture in the younger patients and increased from 70 points at ten weeks to 81 points at two years postoperatively. In the older age group, these scores were 86, 75, and 78 points. The mean WOMAC pain scores before the fracture and at ten weeks and two years postoperatively were 92, 76, and 87 points, respectively, in the younger age group and 92, 84, and 93 points in the older age group. Function scores were 89, 68, and 79 points for the younger age group and 84, 71, and 73 points for the older age group. The Cronbach alpha for pain, stiffness, function, and the total scale ranged from 0.83 to 0.98 for the younger age group and from 0.79 to 0.97 for the older age group. Construct validity was good, with 82% and 79% of predefined hypotheses confirmed in the younger and older age groups, respectively. Responsiveness was moderate. No floor effects were found. Moderate to large ceiling effects were found for pain and stiffness scales at ten weeks and twelve months in younger patients (18% to 36%) and in the older age group (38% to 53%). CONCLUSIONS: The WOMAC showed good reliability, construct validity, and responsiveness in both age groups of elderly patients with a femoral neck fracture who had been physically and mentally fit before the fracture. The instrument is suitable for use in future clinical studies in these populations. CLINICAL RELEVANCE: The results are based on two clinical trials. The questionnaires used concern pure, clinically relevant issues (ability to walk, climb stairs, etc.). Moreover, the results can be used for future research comparing clinical outcomes (or treatments) for populations with a femoral neck fracture.

Severe pain in patients with knee osteoarthritis (OA) hampers the ability to exercise. A protocol for the standardized optimization of analgesics in combination with exercise therapy was developed. The purpose of this protocol was to reduce pain, thereby allowing the patient to participate in exercise therapy. The objective of the present study was to evaluate the feasibility and outcome of the protocol.Forty-nine patients with knee OA and severe knee pain (numerical rating scale for pain ≥7) were included. Analgesics were prescribed following an incremental protocol. After 6 weeks, a 12-week exercise therapy program was added. Information about analgesic use and exercise therapy content was recorded. Knee pain and activity limitations were assessed at baseline, after 6 weeks, and after 18 weeks.Statistically significant improvements in pain and activity limitations were found in intent-to-treat analysis after 6 weeks of analgesic use and after the intervention was completed. Mean improvements from baseline were 30% (P0.001) for pain and 17% (P0.001) for activity limitations after the intervention was completed. Seventy-eight percent of the patients were able to exercise according to the protocol. In these patients, exercise therapy following 6 weeks of analgesic use resulted in a further improvement of activity limitations of 10% (P = 0.004).The combined intervention of standardized analgesic prescription and exercise therapy allows most patients with knee OA and severe pain to participate in exercise therapy, leading to reduction of pain and activity limitations. These promising results need to be confirmed in a randomized controlled trial.

The biological functions of the tumor suppressor ING1 have been studied extensively in the past few years since it was cloned. It shares many biological functions with p53 and has been reported to mediate growth arrest, senescence, apoptosis, anchorage-dependent growth, chemosensitivity, and DNA repair. Some of these functions, such as cell cycle arrest and apoptosis, have been shown to be dependent on the activity of both ING1 and p53 proteins. Two recent reports by Scott and colleagues demonstrate that p33(ING1) (one of the ING1 isoforms) translocates to the nucleus and binds to PCNA upon UV irradiation. Here we report that p33(ING1) mediates UV-induced cell death in melanoma cells. We found that overexpression of p33(ING1) increased while the introduction of an antisense p33(ING1) plasmid reduced the apoptosis rate in melanoma cells after UVB irradiation. We also demonstrated that enhancement of UV-induced apoptosis by p33(ING1) required the presence of p53. Moreover, we found that p33(ING1) enhanced the expression of endogenous Bax and altered the mitochondrial membrane potential. Taken together, these observations strongly suggest that p33(ING1) cooperates with p53 in UVB-induced apoptosis via the mitochondrial cell death pathway in melanoma cells.

To determine whether the perception of body posture is altered in idiopathic scoliosis, a simple neurophysiologic experiment through laser line projection was conducted to test this hypothesis in three groups of individuals: 89 children with idiopathic scoliosis (IS). 50 children with congenital scoliosis (CS) and 45 controls without scoliosis. The subjects were instructed to adjust a laser line projection to the direction of gravity in vertical and in horizontal projections in a dark environment. The performance, expressed as the deviation from the earth vertical (measured in degrees). was calculated by a computer. The three groups fulfilled the vertical and horizontal adjustments within the same accuracy. No relation with age. sex or severity of scoliotic deformity was found. Yet, the angle between vertical and horizontal laser lines was significantly related with the severity of scoliosis, both in IS and CS. In contrast to our hypothesis, it A as concluded that perception Of Postural control in IS is not altered. Therefore, this study indicates that IS is not likely to be caused by a dysfunction of postural control. (C) 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.

To investigate the effect of anti-inflammatory therapy on selective laser trabeculoplasty (SLT) outcomes.Randomized, double-masked, placebo-controlled trial.Patients with primary open-angle or pseudo-exfoliation glaucoma.Patients undergoing SLT were randomized to receive placebo (artificial tears), prednisolone acetate 1%, or ketorolac tromethamine 0.5% eye drops 4 times per day for 5 days commencing immediately after SLT.Change in intraocular pressure (IOP) from baseline to the 1-month post-SLT visit.Mean change in IOP at the 1-month primary outcome time point, as well as all other time points, was not significantly different among groups (P = 0.99). Likewise, a repeated-measures, mixed-effects model did not find significant differences in IOP outcome at the 1-month time point (P = 0.95). The IOP was reduced in all groups at the 1-month post-SLT time point and all other time points, and no significant differences were found between groups using separate unadjusted cross-sectional analyses of variance (P0.15 for analyses at all time points). Treatment failure rates were not different among groups (P = 0.75), and at 1 year after SLT, the percentage of patients maintaining a 20% IOP reduction ranged from 18% to 22% in the 3 study groups.Anti-inflammatory therapy after SLT does not seem to substantially influence the IOP-lowering effect of SLT. In this study of patients with low baseline IOP, SLT showed limited efficacy in achieving a sustained reduction in IOP.

Clinical correlative studies have linked 1p36 deletions with worse prognosis in follicular lymphoma (FL). In this study, we sought to identify the critical gene(s) in this region that is responsible for conferring inferior prognosis. BAC array technology applied to 141 FL specimens detected a minimum region of deletion (MRD) of ∼97 kb within 1p36.32 in 20% of these cases. Frequent single-nucleotide polymorphism–detected copy-neutral loss of heterozygosity was also found in this region. Analysis of promoter CpGs in the MRD did not reveal differential patterns of DNA methylation in samples that differed in 1p36 status. Exon sequencing of MRD genes identified somatic alterations in the TNFRSF14 gene in 3 of 11 selected cases with matching normal DNA. An expanded cohort consisting of 251 specimens identified 46 cases (18.3%) with nonsynonymous mutations affecting TNFRSF14. Overall survival (OS) and disease-specific survival (DSS) were associated with the presence of TNFRSF14 mutation in patients whose overall treatment included rituximab. We further showed that inferior OS and DSS were most pronounced in patients whose lymphomas contained both TNFRSF14 mutations and 1p36 deletions after adjustment for the International Prognostic Index [hazard ratios of 3.65 (95% confidence interval, 1.35–9.878, P = 0.011) and 3.19 (95% confidence interval, 1.06–9.57, P = 0.039), respectively]. Our findings identify TNFRSF14 as a candidate gene associated with a subset of FL, based on frequent occurrence of acquired mutations and their correlation with inferior clinical outcomes. Cancer Res; 70(22); 9166–74. ©2010 AACR.

The secondary genetic events associated with follicular lymphoma (FL) progression are not well defined. We applied genome-wide BAC array comparative genomic hybridization to 106 diagnostic biopsies of FL to characterize regional genomic imbalances. Using an analytical approach that defined regions of copy number change as intersections between visual annotations and a Hidden Markov model–based algorithm, we identified 71 regional alterations that were recurrent in at least 10% of cases. These ranged in size from approximately 200 kb to 44 Mb, affecting chromosomes 1, 5, 6, 7, 8, 10, 12, 17, 18, 19, and 22. We also demonstrated by cluster analysis that 46.2% of the 106 cases could be sub-grouped based on the presence of +1q, +6p/6q−, +7, or +18. Survival analysis showed that 21 of the 71 regions correlated significantly with inferior overall survival (OS). Of these 21 regions, 16 were independent predictors of OS using a multivariate Cox model that included the international prognostic index (IPI) score. Two of these 16 regions (1p36.22-p36.33 and 6q21-q24.3) were also predictors of transformation risk and independent of IPI. These prognostic features may be useful to identify high-risk patients as candidates for risk-adapted therapies.

Study Design. A prospective study in which patients with idiopathic scoliosis were examined longitudinally by radiographic and electromyographic measurements according to a protocol. Objectives. To measure the growth velocity of the spine and the electromyographic ratio of the paraspinal muscles to determine their relation to progression of the scoliotic curve. Summary of Background Data. Several factors have been reported to be involved in the progression of idiopathic scoliosis. Possible factors may be growth disturbances and muscular abnormality. Methods. Thirty patients with idiopathic scoliosis were examined over periods of 4 to 5 months. The periods were scored for progression, defined as an increase in Cobb angle of >10degrees. Spinal growth velocity was measured as the length difference of the scoliotic spine between two consecutive radiographs. The electromyographic activity on both sides of the spine expressed as an electromyographic ratio was measured during relaxed upright standing using bipolar surface electrodes. Predictability of progression was evaluated with regression analysis and receiver operating characteristic analysis. Results. There was an independent association between both spinal growth velocity and electromyographic ratio and progression of the scoliotic curve. An equal sensitivity and specificity of spinal growth velocity for progression of 79.1% was observed at a growth velocity cutoff point of 11 mm/year. Similarly, a cutoff point of 1.25 for the electromyographic ratio could be determined with a predictive value for progression of 68.9%. In the presented nomogram, a spinal growth velocity >15 mm/year combined with an electromyographic ratio >2 gave an 89% probability of progression of the scoliotic deformity. Growth velocities Conclusions. The combined measurement of spinal growth velocity and electromyographic ratio has significant predictive potential and may be valuable in the evaluation and treatment of idiopathic scoliosis.

A transverse force system, consisting of an anterior progression force counteracted by a posterior force and torque, acts on the vertebrae of a scoliotic spine. The aim of the newly introduced TriaC brace is to reverse this transverse force pattern by externally applied and constantly present orthotic forces. In the frontal plane the force system in the TriaC brace is in accordance with the force system of the conventional braces. However, in the sagittal plane the force system acts only in the thoracic region. As a result, there is no pelvic tilt, and it provides flexibility without affecting the correction forces during body motion. In the current preliminary study it is demonstrated that the brace prevents further progression of the Cobb angle and axial rotation in idiopathic scoliosis. The new brace has the added advantage of comfort for the wearer, and it offers a better cosmetic appearance, as well as, potentially, a better compliance. (C) 2002 IPEM. Published by Elsevier Science Ltd. All rights reserved.

Although analysis of scoliotic deformity is still studied extensively by means of conventional roentgenograms, computer-assisted digital analysis may allow a faster, more accurate and more complete evaluation of the scoliotic spine. In this study, a new computer-assisted measurement method was evaluated. This method uses digital reconstruction images for quantitative analysis of the scoliotic spine. The aim of the current study was to determine the reliability of the computer-assisted measuring method, which was done by establishing coefficients of repeatability for a variety of measurements. Measurements were carried out by five observers on 30 frontal and 10 lateral scoliotic digital reconstruction images. Each image was measured on three separate occasions by placing anatomical vertebral landmarks and drawing lines with a computer pointing device. The computer then calculated a number of geometrical shape parameters from scale calibration, landmarks and lines. The intra- and interobserver results were subjected to an analysis of variance to assess the level of agreement, and the means and standard deviations were calculated. The coefficient of repeatability (CR) was taken to be equal to two standard deviations. The mean intraobserver CR was found to be 3.1degrees for the Cobb angle on the frontal digital image and 3.3degrees for the kyphosis Cobb angle on the lateral overview. The mean difference in the intraobserver CR of the Cobb angle between measurements made by placing landmarks and those made by drawing lines was not statistically significant (P>0.05). The mean intraobserver CR for the other parameters can be summarized as follows: for lateral deviation it was 0.8 mm, for axial rotation 4.0degrees and for length of the spine 3.3 mm. The interobserver bias was negligible. It can be concluded that the reliability of our new method for quantifying geometrical variables on digital reconstruction images is better than measurements on conventional roentgenograms in previously published reports. The presented method is therefore considered to be more accurate for research of spinal deformities and more adequate for clinical management of scoliosis.