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1.
Osteoarthritis Cartilage ; 25(9): 1468-1477, 2017 09.
Article in English | MEDLINE | ID: mdl-28506842

ABSTRACT

BACKGROUND: Delayed Gadolinium Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) can detect glycosaminoglycan loss in the acetabular cartilage of asymptomatic individuals with cam morphology. The aims of this study were to explore the relationship between cam morphology and dGEMRIC values, and to explore whether baseline dGEMRIC can predict the development of radiographic hip osteoarthritis. METHODS: Prospective cohort (SibKids) study with clinical, radiographic, and MRI assessment at baseline and five-year follow-up (n = 34). The dGEMRIC values of cartilage regions were correlated with measures of cam morphology. Receiver operating characteristic (ROC) analysis was applied to baseline variables to predict radiographic loss of joint space width. RESULTS: Superolateral acetabular cartilage dGEMRIC values were significantly lower in participants with cam morphology (P < 0.001), defined as an alpha angle greater than 60°. There was a negative correlation between alpha angle and the dGEMRIC value of adjacent acetabular cartilage. This relationship was strongest superoanteriorly (r = -0.697 P < 0.001). There was a positive correlation between baseline dGEMRIC and the magnitude of joint space width narrowing (r = 0.398 P = 0.030). ROC analysis of combined baseline variables (positive impingement test, alpha angle, dGEMRIC ratio) gave an Area Under the Curve (AUC) of 0.75 for predicting joint space width narrowing greater than 0.5 mm within 5 years. CONCLUSIONS: The size and position of cam morphology determines the severity and location of progressive cartilage damage, supporting the biomechanical aetiology of femoroacetabular impingement. Baseline dGEMRIC is able to predict the development of radiographic osteoarthritis. Compositional MRI offers the potential to identify patients who may benefit from early intervention to prevent the development of osteoarthritis.


Subject(s)
Cartilage, Articular/diagnostic imaging , Femoracetabular Impingement/complications , Osteoarthritis, Hip/diagnostic imaging , Osteoarthritis, Hip/etiology , Adult , Aged , Cartilage, Articular/pathology , Contrast Media , Disease Progression , Early Diagnosis , Female , Femoracetabular Impingement/diagnostic imaging , Follow-Up Studies , Gadolinium , Hip Joint/diagnostic imaging , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Osteoarthritis, Hip/pathology , Prognosis , Prospective Studies , Radiography
2.
Bone Joint J ; 97-B(8): 1031-7, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26224817

ABSTRACT

Periprosthetic femoral fracture (PFF) is a potentially devastating complication after total hip arthroplasty, with historically high rates of complication and failure because of the technical challenges of surgery, as well as the prevalence of advanced age and comorbidity in the patients at risk. This study describes the short-term outcome after revision arthroplasty using a modular, titanium, tapered, conical stem for PFF in a series of 38 fractures in 37 patients. The mean age of the cohort was 77 years (47 to 96). A total of 27 patients had an American Society of Anesthesiologists grade of at least 3. At a mean follow-up of 35 months (4 to 66) the mean Oxford Hip Score (OHS) was 35 (15 to 48) and comorbidity was significantly associated with a poorer OHS. All fractures united and no stem needed to be revised. Three hips in three patients required further surgery for infection, recurrent PFF and recurrent dislocation and three other patients required closed manipulation for a single dislocation. One stem subsided more than 5 mm but then stabilised and required no further intervention. In this series, a modular, tapered, conical stem provided a versatile reconstruction solution with a low rate of complications.


Subject(s)
Arthroplasty, Replacement, Hip/instrumentation , Femoral Fractures/surgery , Fracture Fixation, Internal/instrumentation , Hip Prosthesis , Postoperative Complications/surgery , Aged , Aged, 80 and over , Comorbidity , Female , Humans , Male , Middle Aged , Prosthesis Design , Prosthesis Failure , Recurrence , Reoperation , Titanium , Treatment Outcome
3.
Transbound Emerg Dis ; 62(5): e60-1, 2015 Oct.
Article in English | MEDLINE | ID: mdl-24268042

ABSTRACT

Great Britain has been bovine leukaemia virus (BLV) disease free since 1999. We recently reported three separate incidents of BLV seropositivity on farms with home-reared cattle due to the use of colostrum replacer rather than infection with BLV (Emerg. Infect. Dis., 19, 2013, 1027). These cases were all linked via the use of the same brand of colostrum replacer. Here, we investigate further by examining multiple brands of colostrum replacer for proviral DNA and BLV antibodies. BLV antibodies were detected in 7 of the colostrum replacers tested, with PCR concurring in two cases. Thus, the use of these BLV antibody-positive colostrum replacers may also lead to false-positive serological diagnostics.


Subject(s)
Colostrum/virology , Leukemia Virus, Bovine/isolation & purification , Proviruses/genetics , Animals , Antibodies, Viral/analysis , Cattle , Cattle Diseases/diagnosis , Cattle Diseases/immunology , Colostrum/immunology , DNA, Viral/genetics , False Positive Reactions , Female , Leukemia Virus, Bovine/genetics , Leukemia Virus, Bovine/immunology , Polymerase Chain Reaction/veterinary , Pregnancy , United Kingdom
4.
Bone Joint Res ; 3(11): 321-7, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25431439

ABSTRACT

AIMS: Femoroacetabular Junction Impingement (FAI) describes abnormalities in the shape of the femoral head-neck junction, or abnormalities in the orientation of the acetabulum. In the short term, FAI can give rise to pain and disability, and in the long-term it significantly increases the risk of developing osteoarthritis. The Femoroacetabular Impingement Trial (FAIT) aims to determine whether operative or non-operative intervention is more effective at improving symptoms and preventing the development and progression of osteoarthritis. METHODS: FAIT is a multicentre superiority parallel two-arm randomised controlled trial comparing physiotherapy and activity modification with arthroscopic surgery for the treatment of symptomatic FAI. Patients aged 18 to 60 with clinical and radiological evidence of FAI are eligible. Principal exclusion criteria include previous surgery to the index hip, established osteoarthritis (Kellgren-Lawrence ≥ 2), hip dysplasia (centre-edge angle < 20°), and completion of a physiotherapy programme targeting FAI within the previous 12 months. Recruitment will take place over 24 months and 120 patients will be randomised in a 1:1 ratio and followed up for three years. The two primary outcome measures are change in hip outcome score eight months post-randomisation (approximately six-months post-intervention initiation) and change in radiographic minimum joint space width 38 months post-randomisation. ClinicalTrials.gov: NCT01893034. Cite this article: Bone Joint Res 2014;3:321-7.

5.
Oper Dent ; 39(4): 389-97, 2014.
Article in English | MEDLINE | ID: mdl-24967984

ABSTRACT

SUMMARY The aim of this study was to assess the influence of light-curing time on the nanohardness (H) and reduced elastic modulus (Er) of components (underlying dentin, hybrid layer, adhesive, and composite) of methacrylate- and silorane-based restorations after 24 hours and six months of storage. Class II slot preparations were carried out in human molars (n=3) and restored with methacrylate (Clearfil SE Bond [Kuraray] + Filtek Z250 [3M ESPE]) or silorane (LS restorative system [3M ESPE]) restorative systems and light-cured using light-emitting diode at 1390 mW/cm(2) for the recommended manufacturers' time or double time. Restorations were sectioned, and bonded dentin-resin interfaces were embedded in epoxy resin and polished for evaluation with a Berkovich fluid cell tip (TI 700 Ubi-1 nanoindenter, Hysitron). Data were statistically analyzed by analysis of variance and Tukey's test (alpha=0.05). Overall, the H and Er values were higher for methacrylate-based restorations than for silorane materials (p≤0.05), an increase in curing time did not improve the H and Er of the bonded interface components of either material (p>0.05), and aging significantly decreased the mechanical properties of interface components of both resin-based restorative systems (p≤0.05). In general, nanomechanical properties decreased after six months of storage, the methacrylate restorative system exhibited higher H and Er than silorane, and light-curing time did not influence the properties tested.


Subject(s)
Curing Lights, Dental , Dental Restoration, Permanent , Methacrylates , Silorane Resins , Humans , Time Factors
6.
Bone Joint J ; 95-B(6): 825-30, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23723280

ABSTRACT

The Gamma nail is frequently used in unstable peri-trochanteric hip fractures. We hypothesised that mechanical failure of the Gamma nail was associated with inadequate proximal three-point fixation. We identified a consecutive series of 299 Gamma nails implanted in 299 patients over a five-year period, 223 of whom fulfilled our inclusion criteria for investigation. The series included 61 men and 162 women with a mean age of 81 years (20 to 101). Their fractures were classified according to the Modified Evans' classification and the quality of fracture reduction was graded. The technical adequacy of three points of proximal fixation was recorded from intra-operative fluoroscopic images, and technical inadequacy for each point was defined. All patients were followed to final follow-up and mechanical failures were identified. A multivariate statistical analysis was performed, adjusting for confounders. A total of 16 failures (7.2%) were identified. The position of the lag screw relative to the lateral cortex was the most important point of proximal fixation, and when inadequate the failure rate was 25.8% (eight of 31: odds ratio 7.5 (95% confidence interval 2.5 to 22.7), p < 0.001). Mechanical failure of the Gamma nail in peri-trochanteric femoral fractures is rare (< 1%) when three-point proximal fixation is achieved. However, when proximal fixation is inadequate, failure rates increase. The strongest predictor of failure is positioning the lateral end of the lag screw short of the lateral cortex. Adherence to simple technical points minimises the risk of fixation failure in this vulnerable patient group.


Subject(s)
Bone Nails , Fracture Fixation, Intramedullary/instrumentation , Hip Fractures/surgery , Prosthesis Failure , Adult , Aged , Aged, 80 and over , Female , Fluoroscopy , Follow-Up Studies , Hip Fractures/diagnostic imaging , Hip Fractures/physiopathology , Humans , Male , Middle Aged , Prosthesis Design , Range of Motion, Articular , Recovery of Function , Retrospective Studies , Treatment Outcome , Young Adult
7.
Bone Joint Res ; 2(2): 33-40, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23610700

ABSTRACT

OBJECTIVES: The number of surgical procedures performed each year to treat femoroacetabular impingement (FAI) continues to rise. Although there is evidence that surgery can improve symptoms in the short-term, there is no evidence that it slows the development of osteoarthritis (OA). We performed a feasibility study to determine whether patient and surgeon opinion was permissive for a Randomised Controlled Trial (RCT) comparing operative with non-operative treatment for FAI. METHODS: Surgeon opinion was obtained using validated questionnaires at a Specialist Hip Meeting (n = 61, 30 of whom stated that they routinely performed FAI surgery) and patient opinion was obtained from clinical patients with a new diagnosis of FAI (n = 31). RESULTS: Clinical equipoise was demonstrated when surgeons were given clinical scenarios and asked whether they would manage a patient operatively or non-operatively. A total of 23 surgeons (77%) who routinely perform FAI surgery were willing to recruit patients into a RCT, and 28 patients (90%) were willing to participate. 75% of responding surgeons believed it was appropriate to randomise patients to non-operative treatment for ≥ 12 months. Conversely, only eight patients (26%) felt this was acceptable, although 29 (94%) were willing to continue non-operative treatment for six months. More patients were concerned about their risk of developing OA than their current symptoms, although most patients felt that the two were of equal importance. CONCLUSIONS: We conclude that a RCT comparing operative and non-operative management of FAI is feasible and should be considered a research priority. An important finding for orthopaedic surgical trials is that patients without life-threatening pathology appear willing to trial a treatment for six months without improvement in their symptoms.

8.
Osteoarthritis Cartilage ; 21(2): 314-21, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23123686

ABSTRACT

OBJECTIVE: Genetic factors and abnormalities of joint morphology are important in the aetiology of hip osteoarthritis (OA). The extent to which genetic influences are manifest through joint morphology has undergone limited investigation. Using a cohort with an hereditary predisposition to end-stage hip OA and a control group with no inherited risk, we aimed to identify associations with abnormal joint morphology and clinical features. DESIGN: One hundred and twenty-three individuals (mean age 52 years) with a family history of total hip arthroplasty (THA) (termed 'sibkids') were compared with 80 spouse controls. Morphology was assessed using standardised radiographs and cam, dysplasia, and pincer deformities defined. Regression modelling described the association of cohort with abnormal joint morphology, adjusting for confounders [age, gender, body mass index (BMI), OA, and osteophyte]. RESULTS: Sibkids had an odds ratio of 2.1 [95%confidence interval (CI) 1.3-3.5] for cam deformity. There were no differences in the prevalence of dysplasia or pincer deformities. In both groups, hips with cam deformities or dysplasia were more likely to have clinical features than normal hips [odds ratio (OR) 4.46 (1.8-11.3), and 4.40 (1.4-14.3) respectively]. Pincer deformity was associated with positive signs in the sibkids but not in the controls (OR 3.0; 1.1-8.2). DISCUSSION: After adjustment for confounders that cause secondary morphological change, individuals with an hereditary predisposition to end-stage hip OA had a higher prevalence of morphological abnormalities associated with hip OA. Sibkids were more likely to demonstrate clinical features in the presence of pincer deformity, suggesting that the genes are acting not only through abnormal morphology but also through other factors that influence the prevalence of pain.


Subject(s)
Genetic Predisposition to Disease/genetics , Hip Joint/abnormalities , Osteoarthritis, Hip/epidemiology , Osteoarthritis, Hip/genetics , Acetabulum/abnormalities , Acetabulum/diagnostic imaging , Adult , Case-Control Studies , Cohort Studies , Confidence Intervals , Female , Femur/abnormalities , Femur/diagnostic imaging , Hip Joint/diagnostic imaging , Humans , Incidence , Longitudinal Studies , Male , Middle Aged , Odds Ratio , Prospective Studies , Radiography
9.
Osteoarthritis Cartilage ; 20(5): 368-375, 2012 May.
Article in English | MEDLINE | ID: mdl-22343497

ABSTRACT

OBJECTIVE: Genetic factors are important in the aetiology of hip osteoarthritis (OA), but studies are limited by cross-sectional design and poor association with clinically important disease. Identifying cohorts with progressive OA will facilitate development of OA biomarkers. Using a middle-aged cohort with genetic predisposition to hip OA and a control group, we compared the prevalence of clinical and radiographic hip OA and incidence of progression over 5 years. DESIGN: 123 individuals (mean age 52 years) with a family history of total hip arthroplasty (THA) ('sibkids') were compared with 80 (mean age 54 years) controls. The prevalence of radiographic OA [scored according to Kellgren & Lawrence (K&L)], clinical features, and incidence of clinical progression over a 5-year period were compared. A multivariate logistic regression model was used to adjust for confounders. RESULTS: Sibkids had odds ratios (ORs) of 2.7 [95% confidence interval (CI) 1.1-6.3, P = 0.02] for hip OA (K&L grade ≥2), 3.4 (1.4-8.4, P = 0.008) for clinical signs, and 2.1 (0.8-5.8, P = 0.14) for signs and symptoms. Over 5 years, sibkids had ORs of 4.7 (1.7-13.2, P = 0.003) for the development of signs, and 3.2 (1.0-10.3, P = 0.047) for the development of signs and symptoms. DISCUSSION: Compared to a control group and after adjustment for confounders, individuals with genetic predisposition to end-stage hip OA have higher prevalence of OA, clinical features, and progression. In addition to structural degeneration, the inherited risk may include predisposition to pain. Genetically-loaded cohorts are useful to develop hip OA biomarkers, as they develop progressive disease at a young age.


Subject(s)
Osteoarthritis, Hip/genetics , Aged , Arthroplasty, Replacement, Hip , Case-Control Studies , Confounding Factors, Epidemiologic , Disease Progression , Female , Follow-Up Studies , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Osteoarthritis, Hip/diagnostic imaging , Osteoarthritis, Hip/surgery , Radiography
10.
Injury ; 42 Suppl 5: S28-34, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22196907

ABSTRACT

Proximal femoral fractures (PFFs) are a major health concern in the elderly population. Improvements made in implants and surgical techniques resulted in faster rehabilitation and shorter length of hospital stay. Despite this, the reduced physiological reserve, associated co-morbidities and polypharmacy intake of the elderly population put them at high risk of postoperative complications particularly of infectious origin. Out of 10061 patients with proximal femoral fractures 105 (1.05%) developed surgical site infection; 76 (72%) infections occurred in patients who had sustained intracapsular (IC) fractures with the remaining 29 (28%) infections occurring in patients with extracapsular (EC) neck of femur fractures. The median number of additional surgical debridements was 2 (range 1-7). MRSA was isolated in 49 (47%) of the cases; 38 patients (36%) ultimately underwent a Girdlestone's excisional arthroplasty. Mortality at 30 days and 3 months was 10% and 31%, respectively. It was noted that post-operative hip infection predisposed to a prolonged length of stay in the acute unit and subsequently to a more dependent destination after discharge.


Subject(s)
Femoral Fractures/surgery , Postoperative Complications/therapy , Surgical Wound Infection/therapy , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Female , Femoral Fractures/epidemiology , Femoral Neck Fractures/epidemiology , Femoral Neck Fractures/surgery , Femoral Neck Fractures/therapy , Health Care Costs , Hip Fractures/epidemiology , Hip Fractures/surgery , Hip Fractures/therapy , Humans , Length of Stay , Male , Postoperative Complications/epidemiology , Reoperation , Surgical Wound Infection/epidemiology
11.
J Bone Joint Surg Br ; 93(2): 158-63, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21282752

ABSTRACT

We compared the medium-term clinical and radiological results of hybrid total hip replacement (THR) with metal-on-metal Birmingham hip resurfacing (BHR) in two groups of 54 young patients matched for age, gender, body mass index and pre-operative levels of activity. The clinical outcome was assessed by the University of California, Los Angeles (UCLA) activity score, the Oxford Hip Score (OHS) and the EuroQol scores. Radiologically, all hips were assessed for migration and osteolysis, the hybrid THRs for polyethylene wear and the BHRs for a pedestal sign. The mean follow-up of the patients with a hybrid THR was ten years and for those with a BHR, nine years. Four patients with a hybrid THR and one with a BHR had died. In each group five were lost to follow-up. The revision rate of the hybrid THRs was 16.7% (9 of 54) and of the BHRs 9.3% (5 of 54) (p = 0.195). Radiographs of a further eight hybrid THRs demonstrated wear and osteolysis, and they await revision (p = 0.008). Of the unrevised BHRs 90% had radiological changes, of which approximately 50% had progressed over the previous four years. All hybrid THRs demonstrated linear polyethylene wear with a mean of 1.24 mm (0.06 to 3.03). The BHRs recorded superior OHS (p = 0.013), UCLA (p = 0.008), and EuroQol visual analogue scores (p = 0.009). After nine years, patients with BHRs remained more active and had a lower rate of revision than those with hybrid THRs. Both groups demonstrated progressive radiological changes at medium-term follow-up.


Subject(s)
Arthroplasty, Replacement, Hip/methods , Hip Joint/surgery , Osteoarthritis, Hip/surgery , Adolescent , Adult , Aged , Arthroplasty, Replacement, Hip/rehabilitation , Female , Follow-Up Studies , Hip Joint/diagnostic imaging , Hip Joint/physiopathology , Hip Prosthesis , Humans , Male , Middle Aged , Motor Activity , Osteolysis/etiology , Osteolysis/surgery , Patient Satisfaction , Prosthesis Failure , Radiography , Recovery of Function , Reoperation , Treatment Outcome , Young Adult
12.
J Bone Joint Surg Am ; 92(15): 2557-69, 2010 Nov 03.
Article in English | MEDLINE | ID: mdl-21048174

ABSTRACT

BACKGROUND: Cam deformities cause femoroacetabular impingement and damage the acetabular labral-chondral complex. The aims of this study were to investigate the potential of delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) to detect cartilage disease in asymptomatic hips with cam deformities compared with morphologically normal hips, establish whether dGEMRIC could identify advanced disease in hips with positive clinical findings, and establish whether cartilage damage correlated with the severity of the cam deformity. METHODS: Subjects were recruited from a prospective study of individuals with a family history of osteoarthritis and their spouses who served as control subjects. Their symptoms and impingement test results were recorded. Asymptomatic hips with normal radiographic joint-space width were placed in a subgroup according to the presence of a cam deformity and the impingement test result. dGEMRIC was performed on a 3-T system, studying two regions of interest: the anterosuperior aspect of the acetabular cartilage (T1(acet)) and the total femoral and acetabular cartilage (T1(total)). The ratio T1(acet)/T1(total) gave the relative glycosaminoglycan content in the anterosuperior aspect of the acetabular cartilage. The cohort was placed in subgroups by joint morphology, impingement test status, and genetic predisposition; the mean T1 scores were compared, and the alpha angle and T1 were correlated. RESULTS: Of thirty-two subjects (mean age, fifty-two years), nineteen had cam deformities. Hips with a cam deformity had reduced acetabular glycosaminoglycan content compared with normal hips (mean T1(acet)/T1(total), 0.949 and 1.093, respectively; p = 0.0008). Hips with a positive impingement test result had global depletion of glycosaminoglycan compared with hips with a negative result (mean T1(total), 625 ms versus 710 ms; p = 0.0152). T1(acet) inversely correlated with the magnitude of the alpha angle (r = -0.483, p = 0.0038), suggesting that the severity of cartilage damage correlates with the magnitude of the cam deformity. All of these differences occurred irrespective of genetic predisposition. CONCLUSIONS: The dGEMRIC technique can detect cartilage damage in asymptomatic hips with cam deformities and no radiographic evidence of joint space narrowing. This damage correlates with cam deformity severity. Further study of the application of dGEMRIC as an imaging biomarker of early osteoarthritis is justified to validate its prognostic accuracy, identify subjects for clinical trials, and evaluate the effectiveness of surgical procedures.


Subject(s)
Cartilage, Articular/abnormalities , Hip Joint/abnormalities , Magnetic Resonance Imaging/methods , Cartilage, Articular/diagnostic imaging , Contrast Media , Female , Gadolinium DTPA , Hip Joint/diagnostic imaging , Humans , Imaging, Three-Dimensional , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Radiography , Range of Motion, Articular , Reproducibility of Results , Rotation , Statistics, Nonparametric
13.
J Bone Joint Surg Br ; 92(6): 763-9, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20513870

ABSTRACT

Invasive group A streptococcus (iGAS) is the most common cause of monomicrobial necrotising fasciitis. Necrotising infections of the extremities may present directly to orthopaedic surgeons or by reference from another admitting specialty. Recent epidemiological data from the Health Protection Agency suggest an increasing incidence of iGAS infection in England. Almost 40% of those affected had no predisposing illnesses or risk factors, and the proportion of children presenting with infections has risen. These observations have prompted the Chief Medical Officer for the Central Alerting System in England to write to general practitioners and hospitals, highlighting the need for clinical vigilance, early diagnosis and rapid initiation of treatment in suspected cases. The purpose of this annotation is to summarise the recent epidemiological trends, describe the presenting features and outline the current investigations and treatment of this rare but life-threatening condition.


Subject(s)
Fasciitis, Necrotizing/therapy , Streptococcus pyogenes , Adolescent , Adult , Aged , Child , Child, Preschool , England/epidemiology , Fasciitis, Necrotizing/diagnosis , Fasciitis, Necrotizing/epidemiology , Female , Humans , Incidence , Infant , Infant, Newborn , Male , Middle Aged , Young Adult
14.
J Bone Joint Surg Br ; 92(2): 209-16, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20130310

ABSTRACT

Femoroacetabular impingement causes pain in the hip in young adults and may predispose to the development of osteoarthritis. Genetic factors are important in the aetiology of osteoarthritis of the hip and may have a role in that of femoroacetabular impingement. We compared 96 siblings of 64 patients treated for primary impingement with a spouse control group of 77 individuals. All the subjects were screened clinically and radiologically using a standardised protocol for the presence of cam and pincer deformities and osteoarthritis. The siblings of those patients with a cam deformity had a relative risk of 2.8 of having the same deformity (66 of 160 siblings hips versus 23 of 154 control hips, p < 0.00001). The siblings of those patients with a pincer deformity had a relative risk of 2.0 of having the same deformity (43 of 116 sibling hips versus 29 of 154 control hips, p = 0.001). Bilateral deformity occurred more often in the siblings (42 of 96 siblings versus 13 of 77 control subjects, relative risk 2.6, p = 0.0002). The prevalence of clinical features in those hips with abnormal morphology was also greater in the sibling group compared with the control group (41 of 109 sibling hips versus 7 of 46 control hips, relative risk 2.5, p = 0.007). In 11 sibling hips there was grade-2 osteoarthritis according to Kellgren and Lawrence versus none in the control group (p = 0.002). Genetic influences are important in the aetiology of primary femoroacetabular impingement. This risk appears to be manifested through not only abnormal joint morphology, but also through other factors which may modulate progression of the disease.


Subject(s)
Hip Joint/diagnostic imaging , Joint Deformities, Acquired/genetics , Adolescent , Adult , Case-Control Studies , Disease Progression , Female , Genetic Predisposition to Disease , Hip Joint/pathology , Humans , Joint Deformities, Acquired/complications , Joint Deformities, Acquired/diagnostic imaging , Joint Deformities, Acquired/pathology , Male , Middle Aged , Observer Variation , Osteoarthritis, Hip/etiology , Radiography , Reproducibility of Results , Siblings , Young Adult
15.
Nature ; 460(7258): 1031-4, 2009 Aug 20.
Article in English | MEDLINE | ID: mdl-19648907

ABSTRACT

Polymerization of actin filaments directed by the actin-related protein (Arp)2/3 complex supports many types of cellular movements. However, questions remain regarding the relative contributions of Arp2/3 complex versus other mechanisms of actin filament nucleation to processes such as path finding by neuronal growth cones; this is because of the lack of simple methods to inhibit Arp2/3 complex reversibly in living cells. Here we describe two classes of small molecules that bind to different sites on the Arp2/3 complex and inhibit its ability to nucleate actin filaments. CK-0944636 binds between Arp2 and Arp3, where it appears to block movement of Arp2 and Arp3 into their active conformation. CK-0993548 inserts into the hydrophobic core of Arp3 and alters its conformation. Both classes of compounds inhibit formation of actin filament comet tails by Listeria and podosomes by monocytes. Two inhibitors with different mechanisms of action provide a powerful approach for studying the Arp2/3 complex in living cells.


Subject(s)
Actin-Related Protein 2-3 Complex/antagonists & inhibitors , Actin Cytoskeleton/drug effects , Actin Cytoskeleton/metabolism , Actin-Related Protein 2/antagonists & inhibitors , Actin-Related Protein 2/chemistry , Actin-Related Protein 2/metabolism , Actin-Related Protein 2-3 Complex/chemistry , Actin-Related Protein 2-3 Complex/metabolism , Actin-Related Protein 3/antagonists & inhibitors , Actin-Related Protein 3/chemistry , Actin-Related Protein 3/metabolism , Actins/chemistry , Actins/metabolism , Animals , Biopolymers/chemistry , Biopolymers/metabolism , Cattle , Cell Line , Crystallography, X-Ray , Humans , Hydrophobic and Hydrophilic Interactions , Indoles/classification , Indoles/metabolism , Indoles/pharmacology , Listeria/physiology , Models, Molecular , Monocytes/immunology , Protein Conformation/drug effects , Schizosaccharomyces , Thiazoles/chemistry , Thiazoles/classification , Thiazoles/metabolism , Thiazoles/pharmacology , Thiophenes/classification , Thiophenes/metabolism , Thiophenes/pharmacology
16.
J Bone Joint Surg Br ; 91(7): 915-7, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19567856

ABSTRACT

The aim of this study was to investigate genetic influences on the development and progression of tears of the rotator cuff. From a group of siblings of patients with a tear of the rotator cuff and of controls studied five years earlier, we determined the prevalence of tears of the rotator cuff with and without associated symptoms using ultrasound and the Oxford Shoulder Score. In the five years since the previous assessment, three of 62 (4.8%) of the sibling group and one of the 68 (1.5%) controls had undergone shoulder surgery. These subjects were excluded from the follow-up. Full-thickness tears were found in 39 of 62 (62.9%) siblings and in 15 of 68 (22.1%) controls (p = 0.0001). The relative risk of full-thickness tears in siblings as opposed to controls was 2.85 (95% confidence interval (CI) 1.75 to 4.64), compared to 2.42 (95% CI 1.77 to 3.31) five years earlier. Full-thickness tears associated with pain were found in 30 of 39 (76.9%) tears in the siblings and in eight of 15 (53.3%) tears in the controls (p = 0.045). The relative risk of pain associated with a full-thickness tear in the siblings as opposed to the controls was 1.44 (95% CI 2.04 to 8.28) (p = 0.045). In the siblings group ten of 62 (16.1%) had progressed in terms of tear size or development compared to one of 68 (1.5%) in the control group which had increased in size. Full-thickness rotator cuff tears in siblings are significantly more likely to progress over a period of five years than in a control population. This implies that genetic factors have a role, not only in the development but also in the progression of full-thickness tears of the rotator cuff.


Subject(s)
Rotator Cuff Injuries , Shoulder Injuries , Shoulder Pain/genetics , Aged , Aged, 80 and over , Female , Genetic Predisposition to Disease/genetics , Humans , Male , Middle Aged , Rotator Cuff/surgery , Rupture/genetics , Shoulder Joint/surgery , Shoulder Pain/complications , Siblings
17.
J Bone Joint Surg Br ; 90(4): 411-21, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18378911

ABSTRACT

Treatment strategies for osteoarthritis most commonly involve the removal or replacement of damaged joint tissue. Relatively few treatments attempt to arrest, slow down or reverse the disease process. Such options include peri-articular osteotomy around the hip or knee, and treatment of femoro-acetabular impingement, where early intervention may potentially alter the natural history of the disease. A relatively small proportion of patients with osteoarthritis have a clear predisposing factor that is both suitable for modification and who present early enough for intervention to be deemed worthwhile. This paper reviews recent advances in our understanding of the pathology, imaging and progression of early osteoarthritis.


Subject(s)
Arthroplasty, Replacement/methods , Osteoarthritis, Hip/diagnosis , Osteoarthritis, Knee/diagnosis , Aged , Arthroplasty, Replacement/economics , Biomarkers/metabolism , Disease Progression , Early Diagnosis , Humans , Middle Aged , Osteoarthritis, Hip/economics , Osteoarthritis, Hip/surgery , Osteoarthritis, Knee/economics , Osteoarthritis, Knee/surgery
18.
J Bone Joint Surg Br ; 90(3): 280-7, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18310746

ABSTRACT

The majority of patients with osteoarthritis present to orthopaedic surgeons seeking relief of pain and associated restoration of function. Although our understanding of the physiology of pain has improved greatly over the last 25 years there remain a number of unexplained pain-related observations in patients with osteoarthritis. The understanding of pain in osteoarthritis, its modulation and treatment is central to orthopaedic clinical practice and in this annotation we explore some of the current concepts applicable. We also introduce the concept of the 'phantom joint' as a cause for persistent pain after joint replacement.


Subject(s)
Osteoarthritis/physiopathology , Pain/physiopathology , Arthroplasty, Replacement , Humans , Nociceptors/physiology , Orthopedic Procedures , Osteoarthritis/psychology , Osteoarthritis/therapy , Pain/psychology , Pain Management , Pain Measurement , Pain Threshold
19.
J Epidemiol Community Health ; 60(11): 993-7, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17053289

ABSTRACT

OBJECTIVE: To test the validity of age at menarche self-reported in adulthood and examine whether socioeconomic position, education, experience of gynaecological events and psychological symptoms influence the accuracy of recall. DESIGN: Prospective birth cohort study. SETTING: England, Scotland and Wales. PARTICIPANTS: 1050 women from the Medical Research Council National Survey of Health and Development, with two measures of age at menarche, one recorded in adolescence and the other self-reported at age 48 years. RESULTS: By calculating the limits of agreement, kappa statistic and Pearson's correlation coefficients (r), we found that the validity of age at menarche self-reported in middle age compared with that recorded in adolescence was moderate (kappa = 0.35, r = 0.66, n = 1050). Validity was improved by categorising age at menarche into three groups: early, normal and late (kappa = 0.43). Agreement was influenced by educational level and having had a stillbirth or miscarriage. CONCLUSIONS: The level of validity shown in this study throws some doubt on whether it is justifiable to use age at menarche self-reported in middle age. It is likely to introduce error and bias, and researchers should be aware of these limitations and use such measures with caution.


Subject(s)
Menarche , Mental Recall , Abortion, Spontaneous , Adolescent , Age Factors , Educational Status , Female , Health Surveys , Humans , Mental Disorders/psychology , Middle Aged , Prospective Studies , Reproducibility of Results , Social Class , Stillbirth
20.
J Hosp Infect ; 63(2): 133-9, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16621145

ABSTRACT

The purpose of this study was to assess the impact of deep wound infection after surgery for proximal femoral fracture (PFF) on the patient in terms of mortality and social consequences, and on the National Health Service in terms of financial burden. Sixty-one cases of PFF over a six-year period were complicated with deep surgical wound infection. These cases were compared with a matched control group of 122 patients without infection. Infected cases had greatly increased hospital stay (P<0.001), were 4.5 times less likely to survive to discharge (P=0.002), and if they survived, were three times less likely to return to their original residence (P=0.05). The total cost of treatment per infected case was 24,410 pound sterling compared with 7210 pound sterling for controls (P<0.001). Meticillin-resistant Staphylococcus aureus (MRSA) infection increased admission length and cost compared with non-MRSA infection (P=0.02). Deep wound infection after PFF is a devastating and costly complication for both the patient and the healthcare services. The cost consequences should be considered when allocating resources to trauma services to ensure adequate provision to minimize infection risks and to accommodate treatment costs in this vulnerable group.


Subject(s)
Cost of Illness , Cross Infection/economics , Cross Infection/mortality , Fracture Fixation/adverse effects , Hip Fractures/complications , Hospital Costs , Surgical Wound Infection/economics , Surgical Wound Infection/mortality , Aged , Aged, 80 and over , Case-Control Studies , Cross Infection/microbiology , Female , Hip Fractures/surgery , Hospital Mortality , Humans , Length of Stay , Male , Matched-Pair Analysis , Reoperation , Retrospective Studies , Surgical Wound Infection/microbiology , Surgical Wound Infection/therapy , United Kingdom/epidemiology
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