The V(H) repertoire and clonal diversification of B cells in inflammatory myopathies.

The contribution of antigen-driven B-cell adaptive immune responses within the inflamed muscle of inflammatory myopathies (IMs) is largely unknown. In this study, we investigated the immunoglobulin V(H) gene repertoire, somatic hypermutation, clonal diversification, and selection of infiltrating B cells in muscle biopsies from IM patients (dermatomyositis and polymyositis), to determine whether B cells and/or plasma cells contribute to the associated pathologies of these diseases. The data reveal that Ig V(H) gene repertoires of muscle-infiltrating B cells deviate from the normal V(H) gene repertoire in individual patients, and differ between different types of IMs. Analysis of somatic mutations revealed clonal diversification of muscle-infiltrating B cells and evidence for a chronic B-cell response within the inflamed muscle. We conclude that muscle-infiltrating B cells undergo selection, somatic hypermutation and clonal diversification in situ during antigen-driven immune responses in patients with IMs, providing insight into the contribution of B cells to the pathological mechanisms of these disorders.

Do medical student attitudes towards patients with chronic low back pain improve during training? a cross-sectional study.

BACKGROUND: Health care professionals with positive attitudes towards the functional abilities of patients with low back pain are more likely to encourage activity and avoidance of rest as per recommended guidelines. This study investigated whether medical student training fosters positive attitudes towards patients with back pain and their ability to function. METHODS: First (n = 202) and final (n = 146) year medical students at the University of Glasgow completed the Health Care Professionals' Pain and Impairment Relationship Scale (HC-PAIRS) questionnaire. This measures attitudes of clinicians towards the functional ability of patients with back pain. A group of first (n = 62) and final year (n = 61) business students acted as non-health care controls. Attitudes were compared using two-way ANOVA with year of study and discipline of degree as independent variables. RESULTS: Both year of study [F(1,465) = 39.5, p < 0.01] and discipline of degree [F(1,465) = 43.6, p < 0.01] had significant effects on total HC-PAIRS scores and there was a significant interaction effect [F(1,465) = 9.5, p < 0.01]. Medical students commenced their course with more positive attitudes than non-health care students (65.7 vs. 69.2 respectively; p < 0.01)--lower scores translating into more positive attitudes. In their final year, the difference between the two student groups had widened (56.4 vs. 65.3; p < 0.01). CONCLUSIONS: Undergraduate medical training promotes positive attitudes towards the functional ability of patients with back pain, suggesting that students may be more likely to develop an evidence-based approach to this patient group after qualification. Some adjustments to training may be warranted to encourage a more positive shift in attitudes.

Bacterial septic arthritis in adults.

Symptoms and signs of septic arthritis are an important medical emergency, with high morbidity and mortality. We review the changing epidemiology of septic arthritis of native joints in adults, encompassing the increasing frequency of the disorder and its evolving antibiotic resistance. We discuss various risk factors for development of septic arthritis and examine host factors (tumour necrosis factor alpha, interleukins 1 and 10) and bacterial proteins, toxins, and enzymes reported to be important determinants of pathogenesis in mouse models. Diagnosis of disease is largely clinical, guided by investigations and the opinion of skilled clinicians. We emphasise the need for timely medical and surgical intervention-most importantly, through diagnostic aspiration of relevant joints, choice of suitable antibiotic, and appropriate supportive measures. Management is growing in complexity with the advent of novel and antibiotic-resistant causative microorganisms and within the current climate of increased immunosuppression. Findings from animal models and patients are shedding light on disease pathogenesis and the possibility of novel adjunctive treatments, including systemic corticosteroids, cytokines and anticytokines, and bisphosphonates.

Can training in musculoskeletal examination skills be effectively delivered by undergraduate students as part of the standard curriculum?

OBJECTIVES: There is a need to improve competence of musculoskeletal system (MSS) examination in medical students and junior doctors. Peer-assisted learning (PAL) is a technique whereby students learn from and with each other. This study aimed to determine whether PAL can be integrated into standard undergraduate medical curricula to improve MSS examination using the gait, arms, legs, spine (GALS) screening tool. METHODS: Fifty final-year students (trainers) were trained using GALS for MSS examination while attending a standard clinical medical attachment at Glasgow Royal Infirmary. These students delivered GALS training to a further 159 students (trainees). Pre/post-confidence questionnaire (100-mm visual analogue scale) and written feedback were obtained. Final Objective Structured Clinical Examination (OSCE) scores from an MSS station were compared with a control group of 229 students randomized to other hospitals for the standard MSS training. RESULTS: Analysis of completed trainer questionnaires (30/50) showed increased confidence in all parts of GALS after training [<47 (19) cf. >88 (12); P < 0.005]. Similarly, confidence in trainees (136/159) who answered the questionnaire increased [<43 (19) cf. >85 (15); P < 0.005]. Written comments highlighted that students would recommend PAL. OSCE results showed 84% (192/229) of students in the control group passed the MSS station, with 87% (139/159) of trainees (P = 0.3) and 100% (50/50) of trainers (P < 0.01). CONCLUSIONS: MSS examination skills are improved by integrating PAL into the undergraduate medical curriculum, with student confidence being increased, and higher OSCE scores.

Peer-assisted learning in the acquisition of clinical skills: a supplementary approach to musculoskeletal system training.

BACKGROUND: This study evaluates whether peer-assisted learning (PAL) can be used to improve students' clinical examination skills. METHODS: Four year 4 students trained in PAL techniques and musculoskeletal (MSS) examination used the Gait, Arms, Legs and Spine (GALS) system in a five-week student selected module. These students then recruited and trained 28 second-year trainees. Trainees were evaluated using pre/post confidence questionnaires (100 mm visual analogue scale), a course experience questionnaire (five-point Likert scales) and end-of-year objective structured clinical examination (OSCE) scores. RESULTS: Baseline data from the experimental group were no different from a separate control group, but after training a statistically significant difference in confidence levels was observed in all parts of GALS, <38 to >73 (p < 0.0001). Course experience questionnaires demonstrated benefits in all parameters including communication skills and group work with all students recommending PAL training. In end-of-year OSCE 93% of PAL-trained students passed the MSS examination station compared with 67% for those participating in the standard curriculum alone (p < 0.0001). Examination results for other clinical skill stations showed no difference in performance between the two groups. CONCLUSIONS: This study shows that PAL is a useful adjunct to MSS training, and could be incorporated into medical curricula to enhance clinical skills.

Learning contexts at two UK medical schools: a comparative study using mixed methods.

INTRODUCTION: The context in which learning takes place exerts a powerful effect on the approach learners take to their work. In some instances learners will be forced by the nature of a task to adopt a less-favoured approach.In this study, we used a combination of qualitative and quantitative methods to compare the effect of context on learning at different UK medical schools. We compared schools with conventional, and problem-based curricula. METHOD: We had collected data from 30 interviews with third year medical students in one UK medical school with a conventional, lecture-based curriculum in relation to a previous study. The interview guide had explored effects of context and approach to learning. We used the same guide to interview 6 students in another UK medical school with a problem-based curriculum.We then put together a pack of validated questionnaires, which measured the phenomena that had emerged in the interviews. In particular we selected questionnaires which measured the criteria on which students from the different schools appeared to demonstrate greatest variance. RESULTS: There were two areas where students from schools with differing curricula differed - basic learning activity and assessment. Students at the lecture-based school attended lectures where they received information while students at the Problem-based school attended tutorials where they stimulated prior knowledge and identified new learning objectives. Progress -testing at the problem-based school helped students gain a sense of accumulating a body of knowledge needed for their life in medicine while students' at the lecture-based school directed their learning towards passing the next set of exams.The findings from quantitative, questionnaire data correlated with the interview findings. They showed that students at a school with a PBL curriculum scored significantly higher for reflection in learning, self-efficacy in self-directed learning and for deep approach to learning. CONCLUSION: We set out to determine whether students at different medical schools approach their learning differently. We have succeeded in demonstrating that this is the case.The differences that we detected in learning context and approaches to learning in medical students at the two schools predict that learning at the non PBL school is likely to be via a surface approach and not integrated. These differences have major implications for the outcomes of medical student learning at the two schools in terms of accessibility and sustainability of learning.

Peer-assisted learning: a novel approach to clinical skills learning for medical students.

OBJECTIVE: This study aimed to determine whether peer-assisted learning (PAL) can enhance clinical examination skills training. METHODS: Three student trainers studied small-group theory and clinical examination and provided PAL as extra tuition for 86 trainees. Trainees watched an examination video, were videotaped practising the examination and, after constructive feedback, repeated the examination. Responses to PAL were evaluated to attain an overview of trainee and trainer performance using visual analogue and Likert scale analyses. Year-group review was undertaken using questionnaires. RESULTS: Trainees evaluated all aspects of PAL highly, including their post-training confidence in examination skills (mean > 7.7 on a 10-cm scale), indicating that the PAL was effective. Written comments confirmed the students perceived the sessions as well structured and of high quality. Compared with trainees in the first groups, those from later groups gave all parameters similar or higher gradings. Those for interest (P = 0.03) and appropriateness (P = 0.01) were significantly higher, suggesting that trainers may improve their technique with time. Students with previous degrees gave similar or lower gradings than standard entry students, with answers about post-training confidence and recommendation to friends being statistically lower (P < 0.006). Six months later, year-group analysis showed that 90% of trainees rated PAL highly, and 86% wished to become trainers. Of the trainers' year group, 79% perceived that PAL training could improve examination skills. CONCLUSIONS: In the context of clinical skills training, PAL was highly evaluated across many parameters, including confidence after training. Student interest and enthusiasm supports suggestions that PAL could be a useful adjunct to clinical skills training.

The importance of the disease process and disease-modifying antirheumatic drug treatment in the development of septic arthritis in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the effect of disease-modifying antirheumatic drugs (DMARDs) on the likelihood of patients with rheumatoid arthritis (RA) developing septic arthritis (SA). METHODS: The United Kingdom General Practice Research Database (GPRD) was used to identify adults with RA, and age-, sex-, and practice-matched control subjects. Subjects were studied between 1987 and 2002. The risk of developing SA (excluding infected joint replacements) for individuals with RA was calculated and the effect of DMARD use determined. RESULTS: A total of 136,977 subjects (34,250 patients with RA, 102,747 controls) were identified. SA was identified in 345 subjects, of which 321 (236 in patients with RA, 85 in controls) cases occurred during the study period. The incidence rate of SA was 12.9 times higher in subjects with RA than in those without (95% confidence interval [95% CI] 10.1-16.5, P < 0.001). The incident rate ratios (IRRs) for developing SA while receiving DMARDs compared with receiving no DMARDs were different for different medications. Penicillamine (adjusted IRR 2.51, 95% CI 1.29-4.89, P = 0.004), sulfasalazine (adjusted IRR 1.74, 95% CI 1.04-2.91, P = 0.03), and prednisolone (adjusted IRR 2.94, 95% CI 1.93-4.46, P < 0.001) were associated with an increased incidence of SA when compared with not receiving any DMARD. The use of other DMARDs including methotrexate showed no such effect. CONCLUSION: Individuals with RA have an increased risk of developing SA. This increased risk can be attributed to both the disease process and the use of DMARDs.

The heterogeneity of the glycosylation of alpha-1-acid glycoprotein between the sera and synovial fluid in rheumatoid arthritis.

Alpha-1-acid glycoprotein (AGP) is a plasma glycoprotein produced by the liver that undergoes increased production and altered glycosylation in several physiological and pathological conditions including rheumatoid arthritis. To date, although present in the synovial fluid of rheumatoid arthritis patients, there has been no evidence for the separate extra-hepatic production of AGP. This study indicates that there could be a localized production of AGP in rheumatoid synovial fluid by demonstrating that the glycosylation patterns of AGP differed between the serum and synovial fluid in the same rheumatoid patient. Serum AGP was largely composed of fucosylated tri- and tetra-antennary oligosaccharide chains while the synovial fluid contained mainly bi-antennary chains that were fucosylated to a lesser extent. This structural heterogeneity of glycosylation resulted in functional diversity; serum but not synovial AGP is able to inhibit binding to the cell adhesion molecule E-selectin through expression of antigen sialyl Lewis X.

The VH gene repertoire of splenic B cells and somatic hypermutation in systemic lupus erythematosus.

In systemic lupus erythematosus (SLE) it has been hypothesized that self-reactive B cells arise from virgin B cells that express low-affinity, nonpathogenic germline V genes that are cross-reactive for self and microbial antigens, which convert to high-affinity autoantibodies via somatic hypermutation. The aim of the present study was to determine whether the VH family repertoire and pattern of somatic hypermutation in germinal centre (GC) B cells deviates from normal in SLE. Rearranged immunoglobulin VH genes were cloned and sequenced from GCs of a SLE patient's spleen. From these data the GC V gene repertoire and the pattern of somatic mutation during the proliferation of B-cell clones were determined. The results highlighted a bias in VH5 gene family usage, previously unreported in SLE, and under-representation of the VH1 family, which is expressed in 20-30% of IgM+ B cells of healthy adults and confirmed a defect in negative selection. This is the first study of the splenic GC response in human SLE.

Ultrasound guided versus conventional joint and soft tissue fluid aspiration in rheumatology practice: a pilot study.

OBJECTIVE: To compare joint and soft tissue aspiration using a conventional technique with an ultrasound (US) guided technique. METHODS: In the conventional group, 32 joints in 30 consecutive patients referred for joint aspiration and injection to an experienced consultant rheumatologist were aspirated. In the US guided group, 31 consecutive patients were examined by US to confirm the presence and location of fluid. Following US examination, aspiration was performed by a second rheumatologist based on the US localization of fluid or under direct US guidance. RESULTS: In the conventional group, successful aspiration was achieved in 10 (32%) joints. In the US guided group, successful aspiration was achieved in 31 (97%) joints. The mean volume of fluid obtained from successful aspirations was similar in both groups (11.7 ml in the US group and 14 ml in the conventional group). CONCLUSION: The use of US to localize joint and soft tissue fluid collection greatly improves the rate of diagnostic synovial fluid aspiration, particularly in small joints. This has important implications for accurate administration of local steroid therapy and emphasizes the importance of US as a useful tool in clinical rheumatological practice.