Association between Bone marrow lesions & synovitis and symptoms in symptomatic knee osteoarthritis.

OBJECTIVE: Bone marrow lesions (BMLs) on MRI are typically subchondral in location, however, a proportion occur at knee ligament attachments and also include a cyst-like component. Our aim was to determine whether the volume of BML subtypes and synovial tissue volume (STV) was associated with symptoms in symptomatic knee OA. METHOD: Images were acquired in a sub-sample who had taken part in a randomised trial of vitamin D therapy in knee OA (UK-VIDEO). Contrast-enhanced (CE) MRI was performed annually. In those who had ≥1 follow-up and a baseline scan (N = 50), STV and BML volume was assessed. BMLs were categorised by location and by the presence/absence of a cyst-like component. WOMAC was assessed annually. We used fixed-effects panel-regression modelling to examine the association between volume and symptoms. RESULTS: There was no association between knee pain and total subchondral BML volume (b = 0.3 WOMAC units, 95% CI -0.3 to 1.0) or total ligament-based BML volume (b = 1.9, 95% CI -1.6 to 5.3). The volume of subchondral BMLs with a cyst-like component was not associated with pain (b = 0.8, 95% CI -0.5 to 2.1) however, the volume of the cyst-like component itself was associated with pain (b = 51.8, 95% CI 14.2 to 89.3). STV was associated with pain (b = 2.2, 95% CI 0.6 to 3.7). CONCLUSION: The volume of the cyst-like component from subchondral BMLs with a cyst-like component was associated with knee pain. BML location, however, did not influence symptoms. STV was also associated with knee symptoms.

Role of vascular channels as a novel mechanism for subchondral bone damage at cruciate ligament entheses in osteoarthritis and inflammatory arthritis.

OBJECTIVES: The purpose of this work was to test whether normal peri-entheseal vascular anatomy at anterior and posterior cruciate ligaments (ACL and PCL) was associated with distribution of peri-entheseal bone erosion/bone marrow lesions (BMLs) in inflammatory arthritis (IA) and osteoarthritis (OA). METHODS: Normal microanatomy was defined histologically in mice and by 3 T MRI and histology in 21 cadaveric knees. MRI of 89 patients from the Osteoarthritis Initiative and 27 patients with IA was evaluated for BMLs at ACL and PCL entheses. Antigen-induced arthritis (AIA) in mice was evaluated to ascertain whether putative peri-entheseal vascular regions influenced osteitis and bone erosion. RESULTS: Vascular channels penetrating cortical bone were identified in knees of non-arthritic mice adjacent to the cruciate ligaments. On MRI of normal cadavers, vascular channels adjacent to the ACL (64% of cases) and PCL (71%) entheses were observed. Histology of 10 macroscopically normal cadaveric specimens confirmed the location of vascular channels and associated subclinical changes including subchondral bone damage (80% of cases) and micro-cyst formation (50%). In the AIA model, vascular channels clearly provided a site for inflammatory tissue entry and osteoclast activation. MRI showed BMLs in the same topographic locations in both patients with early OA (41% ACL, 59% PCL) and IA (44%, 33%). CONCLUSION: The findings show that normal ACL and PCL entheses have immediately adjacent vascular channels which are common sites of subtle bone marrow pathology in non-arthritic joints. These channels appear to be key determinants in bone damage in inflammatory and degenerative arthritis.

Potential role of the posterior cruciate ligament synovio-entheseal complex in joint effusion in early osteoarthritis: a magnetic resonance imaging and histological evaluation of cadaveric tissue and data from the Osteoarthritis Initiative.

OBJECTIVE: This study explored posterior cruciate ligament (PCL) synovio-entheseal complex (SEC) microanatomy to determine whether it may participate in the early osteoarthritis (OA) disease process. METHODS: SEC microanatomy and OA features were evaluated in 14 non-arthritic cadaveric knees (mean age = 69.9) using magnetic resonance imaging (MRI) and histology. MRI images of 49 subjects selected from the progression cohort of the Osteoarthritis Initiative (OAI) were evaluated by a musculoskeletal radiologist using an original semi-quantitative method for features associated with OA at the PCL tibial enthesis. Statistical analysis was performed using chi-square and Wilcoxon signed-rank tests to evaluate associations between SEC configuration and OA features. RESULTS: The PCL formed a SEC-like structure encompassing bone- and ligament-lining intra-articular cartilages to which the posterior root of the medial meniscus contributed. Degenerative features at the PCL-SEC included: neovascularisation (44%), enthesis chondrocyte clustering (44%), collagen matrix fissuring at the enthesis (56%) and in the PCL itself (67%), tidemark duplication (44%), bone remodelling (44%) and microscopic inflammatory changes (33%). In the OAI cohort, SEC-related pathology included bone marrow lesions (BMLs) (69%) and osteophytosis (94%) at locations that corresponded to SEC-related cartilages. Posterior joint recess effusion (49%) was linked to MRI abnormalities at PCL-SEC cartilages (χ2 = 7.27, P = 0.007). CONCLUSIONS: The PCL has a prominent SEC configuration that is associated with microscopic OA changes in aged clinically non-diseased joints. MRI determined knee OA commonly exhibited pathological features at this site which was associated with adjacent joint effusion. Thus, the PCL-SEC could play a hitherto unappreciated role in the early OA disease process.

Quantitative parametric MRI of articular cartilage: a review of progress and open challenges.

With increasing life expectancies and the desire to maintain active lifestyles well into old age, the impact of the debilitating disease osteoarthritis (OA) and its burden on healthcare services is mounting. Emerging regenerative therapies could deliver significant advances in the effective treatment of OA but rely upon the ability to identify the initial signs of tissue damage and will also benefit from quantitative assessment of tissue repair in vivo. Continued development in the field of quantitative MRI in recent years has seen the emergence of techniques able to probe the earliest biochemical changes linked with the onset of OA. Quantitative MRI measurements including T(1), T(2) and T(1ρ) relaxometry, diffusion weighted imaging and magnetisation transfer have been studied and linked to the macromolecular structure of cartilage. Delayed gadolinium-enhanced MRI of cartilage, sodium MRI and glycosaminoglycan chemical exchange saturation transfer techniques are sensitive to depletion of cartilage glycosaminoglycans and may allow detection of the earliest stages of OA. We review these current and emerging techniques for the diagnosis of early OA, evaluate the progress that has been made towards their implementation in the clinic and identify future challenges in the field.

Contrast-enhanced MRI of the subdeltoid, subacromial bursa in painful and painless rotator cuff tears.

OBJECTIVE: Although shoulder pain is often associated with rotator cuff tears, many tears are asymptomatic and are not the cause of the patient's pain. This may explain the persistence of symptoms in some patients despite technically successful rotator cuff repair. It has been proposed that rotator cuff tears cause pain through subdeltoid/subacromial bursal inflammation. The aim of this study was to determine whether bursal inflammation seen on MRI is associated with pain in patients with rotator cuff tears of the shoulder. METHODS: The shoulders of 255 patients were screened with ultrasound. 33 full-thickness rotator cuff tears (18 with shoulder pain and 15 without pain) were identified and subsequently studied using contrast-enhanced MRI of the shoulder. Enhancement of the subacromial bursa was scored independently by two musculoskeletal radiologists. Logistic regression was used to determine whether bursal enhancement was independently associated with pain. RESULTS: There was a significant association between pain and age, with greater likelihood of pain in younger patients. Bursal enhancement was common in both painful and painless tears. No statistically significant link between pain and bursal enhancement was seen, even after accounting for age. CONCLUSION: Although enhancement of the subdeltoid/subacromial bursa was common, no evidence was found to support the hypothesis that bursal enhancement is associated with pain in rotator cuff tears. It is therefore unlikely to determine reliably which patients would benefit from rotator cuff repair. Advances in knowledge Bursal enhancement and thickening does not reliably correlate with symptoms or presence of rotator cuff tear.

Quantitative MRI measurements of the Achilles tendon in spondyloarthritis using ultrashort echo times.

OBJECTIVES: Tendon involvement is common in spondyloarthritis. The MRI signal from the Achilles tendon has been used to quantify mechanical tendinopathy; however, conventional MRI is limited by the short T(2) of normal tendon. Short and ultrashort echo time (UTE) MRI have the potential to better measure signal intensity reflecting changes in T(2) or gadolinium enhancement. Furthermore, UTE images could be used for normalisation to reduce variability. The aim of this work was to investigate such techniques in patients with spondyloarthritis (SpA). METHODS: The Achilles tendons of 14 healthy volunteers and 24 patients with symptomatic spondyloarthritis were studied. Combined UTE (TE=0.07 ms) and gradient echo (TE=4.9 ms) images were acquired before and after intravenous gadolinium together with pre-contrast gradient echo images (TE=2 ms). The signal intensity from a region of interest in the Achilles tendon above the calcaneus was measured. The relative enhancement at echo times of 0.07 ms (RE(0.1)) and 4.9 ms (RE(5)) were calculated. The ratios of the signal intensities from both 4.9 ms and 2 ms gradient echo images to the signal intensity from the UTE image were calculated (RTE(5) and RTE(2) respectively). RESULTS: Interobserver intraclass correlation coefficients were excellent (≥0.97). The contrast-to-noise ratio was higher for enhancement on UTE images than on gradient echo images. RE(0.1), RTE(5) and RTE(2) were significantly higher in SpA patients than controls. CONCLUSION: Signal intensity ratios using UTE images allow quantitative measurements to be made which are sensitive to tendon T(2) or contrast enhancement and which are increased in spondyloarthritis. They therefore have the potential for use as measures of tendon disease in spondyloarthritis.

Tendon and ligament imaging.

MRI and ultrasound are now widely used for the assessment of tendon and ligament abnormalities. Healthy tendons and ligaments contain high levels of collagen with a structured orientation, which gives rise to their characteristic normal imaging appearances as well as causing particular imaging artefacts. Changes to ligaments and tendons as a result of disease and injury can be demonstrated using both ultrasound and MRI. These have been validated against surgical and histological findings. Novel imaging techniques are being developed that may improve the ability of MRI and ultrasound to assess tendon and ligament disease.

Imaging of the Achilles tendon in spondyloarthritis: a comparison of ultrasound and conventional, short and ultrashort echo time MRI with and without intravenous contrast.

OBJECTIVES: To compare conventional MRI, ultrashort echo time MRI and ultrasound for assessing the extent of tendon abnormalities in spondyloarthritis. METHODS: 25 patients with spondyloarthritis and Achilles symptoms were studied with MRI and ultrasound. MR images of the Achilles tendon were acquired using T1-weighted spin echo, gradient echo and ultrashort echo time (UTE) sequences with echo times (TE) between 0.07 and 16 ms, before and after intravenous contrast medium. Greyscale and power Doppler ultrasound were also performed. The craniocaudal extent of imaging abnormalities measured by a consultant musculoskeletal radiologist was compared between the different techniques. RESULTS: Abnormalities were most extensive on spoiled gradient echo images with TE = 2 ms. Contrast enhancement after intravenous gadolinium was greatest on the UTE images (TE = 0.07 ms). Fewer abnormalities were demonstrated using unenhanced UTE. Abnormalities were more extensive on MRI than ultrasound. Contrast enhancement was more extensive than power Doppler signal. CONCLUSIONS: 3D spoiled gradient echo images with an echo time of 2 ms demonstrate more extensive tendon abnormalities than the other techniques in spondyloarthritis. Abnormalities of vascularity are best demonstrated on enhanced ultrashort echo time images.

Luus-Jaakola optimization procedure for phase-only sampled-fiber Bragg gratings.

We describe a Luus-Jaakola (LJ) optimization algorithm approach for the design of wavelength division multiplexing (WDM) optical communication systems by using phase-only sampled-fiber Bragg gratings. The LJ method is used to optimize the phase grating as well as the number of segments which form the grating. The numerical example of WDM is studied. The method is easily applicable and shows promising results with low refractive index modulation.

Optimization of multilayer mirrors at 13.4 nm with more than two materials.

The design of multilayer mirrors with more than two materials is one of the key technologies for investigating lithography. We study a new procedure for optimizing multilayer mirrors of different combinations of materials at a wavelength of 13.4 nm. By adding Be and C layers in different orders to a Si/Mo stack, we have observed enhancement of the reflectivity and a reduction in the number of layers. The Luus-Jaakola optimization procedure has been implemented for the global optimization of the multilayer mirrors. With this algorithm it is not necessary to specify initially the number of layers present in a given design.

MRI of rheumatoid arthritis image quantitation for the assessment of disease activity, progression and response to therapy.

Magnetic resonance imaging (MRI) allows the direct visualization of many bone and soft tissue changes in rheumatoid arthritis. Synovitis volume, bone marrow oedema and bone erosions are suitable for serial measurement. The outcome measures in rheumatoid arthritis clinical trials (OMERACT) rheumatoid arthritis magnetic resonance imaging (RAMRIS) system is designed to allow straightforward, reproducible scoring of all these features. Alternatively, synovial volumes may be directly and quickly measured using semi-automated techniques. There is the potential for similar systems for measuring erosions. Dynamic contrast enhanced MRI depends on the rate of enhancement of the synovium after intravenous contrast agent. Measurements depend on the underlying physiology of the inflamed synovium, in particular the vascularity and capillary permeability which are expected to closely mirror inflammatory activity in the joint. Measurements from MRI have been shown to correlate with clinical, laboratory, imaging and histological measures of inflammation, predict erosive progression and respond rapidly to various types of treatment. They are, therefore, expected to be good measures of disease activity, progression and response to therapy.

The addition of a psychological intervention to a home detoxification programme.

AIMS: Home detoxification is a recognized method of treating problem drinkers within their own home environment. The aim of this research is to determine whether a relatively brief psychological intervention adds to its effectiveness. METHODS: A pragmatic trial with 91 participants randomly assigned to either the psychological intervention or treatment as usual. Community Psychiatric Nurses were trained to administer the brief psychological intervention involving motivational interviewing, coping skills training and social support. A manual was developed in order to standardize the training and implementation. RESULTS: At the 3 month and 12 month follow-up the psychological intervention resulted in significant positive changes in alcohol consumption, abstinent days, social satisfaction, self-esteem and alcohol-related problems. Further, a cost analysis confirmed that the psychological intervention was a ninth of the cost of inpatient treatment. CONCLUSIONS: Adding a psychological intervention to a home detoxification programme was successful and cost-effective.

A randomized controlled trial of a brief intervention after alcohol-related facial injury.

AIM: To evaluate the effectiveness of a brief motivational intervention on alcohol consumption and misuse in young males with alcohol-related face injury. DESIGN: Randomized controlled trial. SETTING: Oral and maxillofacial surgery out-patient clinic in an urban teaching hospital. PARTICIPANTS: One hundred and fifty-one participants were randomized to motivational intervention and control conditions. INTERVENTIONS: Control was treatment as usual. The intervention was treatment as usual plus a one-session brief motivational intervention administered by a nurse. MEASUREMENTS: Three sets of measurements were taken at baseline, 3-month and 1-year follow-up. Collateral measurements were also taken at 1-year follow-up. Primary outcome measures were total alcohol consumption, typical weeks consumption and days abstinent in preceding 3 months. Other outcome measures included the Alcohol Use Disorders Identification Test, a short form of the Alcohol Problems Questionnaire, and a measure of satisfaction with social relationships. RESULTS: There was a significant decrease in 84-day total alcohol consumption across the year (P < 0.006) and further, a significant effect for the motivational intervention was demonstrated (P < 0.029). This pattern was repeated for days abstinent and alcohol consumption in a typical week as well as alcohol-related problems. There was a significantly greater reduction in the percentage of hazardous drinkers in the motivational intervention group (from 60% to 27%, P < 0.009) compared to the control group (from 54% to 51%, NS). CONCLUSION: A proportion of young men change their alcohol consumption following alcohol-related injury. A nurse-led psychological intervention adds significantly to the proportion and magnitude of response.

Effects of glucose and fluoride on competition and metabolism within in vitro dental bacterial communities and biofilms.

Antimicrobial effects of fluoride in vivo remain contentious. Previous studies suggested that 1 mM NaF reduced acid production from glucose, and prevented the enrichment of bacteria associated with caries in a chemostat model. The present study examines the effects of a lower fluoride concentration (0.53 mM, 10 ppm NaF) in both biofilm and planktonic microbial communities. Nine oral species were grown at pH 7.0 and pulsed on 10 successive days with glucose; bacterial metabolism was allowed to reduce the pH for 6 h before being returned to neutrality, either in the presence or absence of NaF. In addition, 10-day-old mixed culture biofilms were overlaid with glucose, with or without NaF, and the pH change followed by microelectrode. After 10 days, chemostat pH dropped to ca. pH 4.5 following glucose pulses, and the community was dominated by Streptococcus mutans (rising from 4 to 23% of total CFU) and Veillonella dispar (16 to 73%). In comparison, after 10 days pulsing with glucose + fluoride, the final pH was significantly higher (ca. pH 4.9) (paired t test, p < 0.0001). The culture was predominated by V. dispar (70%) and Actinomyces naeslundii (13%), whereas S. mutans proportions were significantly lower (t test, p = 0.04), remaining <3% of the total flora, compared to the culture without fluoride. Biofilm pH fell to only pH 5.55 1 h after glucose/fluoride overlay, compared to 4.55 with glucose alone (paired t test, p < 0.000001). Analysis of the data suggests that fluoride exerts dual antimicrobial modes of action. Fluoride prevents enrichment of S. mutans by inhibiting critical metabolic processes (direct effect) and, in an inter-related way, by reducing environmental acidification (indirect effect) in biofilms.

Genetic Algorithm Approach to the Determination of Particle Size Distributions from Static Light-Scattering Data.

The application of genetic algorithms to the inversion of static light-scattering (SLS) measurements is investigated. The approach is illustrated using simulated data on samples with unimodal, bimodal, and trimodal distributions of spherical particles. Particles having diameters in the range from 100 to 4000 nm are treated. Results are compared with other inversion procedures. It is found that genetic algorithms yield very good results in this situation. Copyright 2001 Academic Press.

A continuous culture biofilm model of cariogenic responses.

AIMS: To validate an in vitro model for the analysis of physiological and ecological responses to sugar challenge in bacterial populations, and subsequent changes in enamel mineralization. METHODS AND RESULTS: A seven-organism bacterial consortium was grown in a biofilm mode on enamel and hydroxyapatite (HA) surfaces in a continuous culture system and exposed to repeated sucrose challenges. This produced 'pH-cycling' conditions within the system. Populations on HA surfaces were enumerated. Changes in relative proportions of the different populations, and in the total viable count, were observed, between different treatments. Microradiography of the enamel sections showed increasing demineralization with increasing sucrose concentration. The lesions formed were similar to 'white-spot' lesions found in vivo. Differences in the quality of biofilms formed were also observed using Confocal Laser Scanning Microscopy. CONCLUSION: An in vitro model has been validated for the analysis of both physiological and ecological responses to sucrose challenges in bacterial populations, and subsequent changes in enamel mineralization. SIGNIFICANCE AND IMPACT OF THE STUDY: This model should facilitate the study of changes in bacterial populations in response to application of putative anticaries agents and concomitant changes in enamel mineralization.

Goonery in British clinical psychology: the Duracic spark.

Stanley Rachman, known to his colleagues as Jack Durac, has had a powerful influence on British clinical psychology. It is hypothesised that Duracic goonery has played a major role in the development of new treatments, as well as in the training of new clinical psychologists. Objective, historical evidence is assembled to support the view that this Duracic spark should be brought out into the field of scientific discourse and should not be hidden behind more comfortable jargon.

A fluorescence study of ligand-induced conformational changes in cytosolic fructose-1,6-bisphosphatase from germinating castor oil seeds.

The intrinsic fluorescence of homogeneous castor oil seed cytosolic fructose-1,6-bisphosphatase (FBPasec) was used as an indicator of conformational changes due to ligand binding. Binding of the substrate and the inhibitor fructose-2,6-bisphosphate (F-2,6-P2) was quantitatively compared to their respective kinetic effects on enzymatic activity. There are two distinct types of substrate interaction with FBPasec, corresponding to catalytic and inhibitory binding, respectively. Inhibitory substrate binding shares several characteristics with F-2,6-P2 binding which indicates that both ligands bind at the same site. However, F-2,6-P2 does not prevent fluorescence transitions attributed to catalytic substrate binding. The marked synergistic inhibition of FBPasec by AMP and F-2,6-P2 appears to arise via AMP's promotion of F-2,6-P2 binding. Based on the X-ray crystal structure of porcine kidney FBPase our modelling studies suggest the existence of a distinct F-1,6-P2/F-2,6-P2 inhibitory binding site which partially overlaps with the enzyme's catalytic site. We propose that a pronounced allosteric transition mediated by AMP binding increases access of F-1,6-P2 and F-2,6-P2 to this common inhibitory binding site.

Purification and characterization of cytosolic fructose-1, 6-bisphosphate aldolase from endosperm of germinated castor oil seeds.

Cytosolic fructose-1,6-bisphosphate (FBP) aldolase (ALDc) from the endosperm of 4- to 5-day germinated castor oil seeds (COS) has been purified 83-fold to electrophoretic homogeneity and a final specific activity of 2.5 micromol FBP cleaved/min/mg protein. SDS-PAGE and denaturing isoelectric focusing of the final preparation revealed a single protein-staining band of 40 kDa and pI value 7.2. The native Mr was determined by gel-filtration chromatography and multiangle laser light scattering to be 160-175 kDa, indicating that the enzyme is homotetrameric. The enzyme (a) is a class I aldolase, since EDTA or Mg2+ had no effect on its activity; and (b) was relatively heat stable and had an activation energy of 100 kJ/mol. It exhibited a broad pH-activity optima of 7.2, a relatively high affinity for FBP (Km = 0.16 microM), and a forward:reverse Vmax ratio of 0.77. Rabbit anti-(COS ALDc) antibodies cross-reacted with COS ALDc, but not with the corresponding plastidic isozyme. Time-course studies revealed that (a) the increase in total ALD activity that occurs during COS development and early germination coincides with an increase in ALDc concentration and (b) the latter stages of COS maturation and germination are accompanied by marked reductions in ALD activity and ALDc concentration. The most significant elevation in ALDc concentration occurred over the first 4 days of germination when COS initiates the gluconeogenic conversion of P-enolpyruvate and triose-P, derived from reserve triacylglycerols, into the sucrose required to support early seedling growth.

Brief interventions for patients with alcohol-related trauma.

Patients who have sustained alcohol-related injuries are frequently treated in departments of oral and maxillofacial surgery. Often, an alcohol intervention will not be possible in accident and emergency departments due to intoxication but, when attending out-patient clinics for follow-up, patients are usually sober. This presents a unique opportunity for encouraging patients to review their alcohol consumption at a time when their facial injury may make them more receptive to advice. This article reviews the convincing evidence of the effectiveness of advice and brief interventions designed to be incorporated into standard out-patient consultations and describes practical screening of patients for harmful drinking, the Stages of Change Model of behaviour change and motivational interviewing for facilitating behavioural change.