ABSTRACT
AIM: To examine the magnetic resonance imaging (MRI) features of the ankle and subtalar joints that might distinguish genetic haemochromatosis (GH). MATERIALS AND METHODS: The present study was a retrospective case-control study comparing 30 MRI studies of GH patients with ankle or subtalar arthropathy with 30 matched controls with ankle pain. Anonymised images were scored using a semi-quantative tool adapted from the MRI osteoarthritis knee score. Scores were generated for bone marrow lesions size, number, and distinguishing the proportion of each lesion consisting of subchondral cyst versus oedema. Articular cartilage loss and osteophytes were documented. The primary comparator was bone marrow lesion size. Paired Student's t-test and the chi-squared test were utilised to compare outcomes. RESULTS: Bone marrow lesion/cyst size and number, presence and extent of full-thickness cartilage loss, and osteophyte scores were significantly higher in ankle joints of GH cases (p<0.01). In the middle subtalar articulation, there were significantly higher scores for full-thickness cartilage loss and extent and osteophytes in GH cases (p<0.05). There were no significant differences in the posterior subtalar articulation. CONCLUSION: The finding of both numerous and large cysts on ankle MRI should raise suspicion of GH. Other MRI features of potential diagnostic value include large osteophytes and the presence of extensive full-thickness cartilage loss in the ankle joint and middle subtalar articulation.
Subject(s)
Ankle Joint/diagnostic imaging , Hemochromatosis/diagnostic imaging , Magnetic Resonance Imaging/methods , Subtalar Joint/diagnostic imaging , Adult , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged , Pain Measurement , Retrospective StudiesABSTRACT
Anaemia is prevalent in patients with systemic lupus erythematosus (SLE). The anaemia is often a consequence of the disease itself but may also be secondary to drug treatments. Mycophenolate mofetil (MMF) is increasingly used in the management of patients with SLE and its associated anaemia. We describe the case of a 19-year-old girl, who presented acutely with SLE and renal involvement. Her disease was controlled with immunosuppression but she later developed severe transfusion-dependent anaemia. Several causes were considered before a bone marrow biopsy led to the diagnosis of erythroid hypoplasia. In the absence of clinical or laboratory markers of active lupus, MMF was implicated as the cause. Its discontinuation led to a rapid and sustained correction of the anaemia. Red cell aplasia linked to the use of MMF is uncommon and the manufacturers are aware of fewer than 50 cases. This is the first case report of evolving red cell aplasia induced by MMF in SLE.
Subject(s)
Immunosuppressive Agents/adverse effects , Lupus Erythematosus, Systemic/drug therapy , Mycophenolic Acid/analogs & derivatives , Red-Cell Aplasia, Pure/chemically induced , Anemia/etiology , Female , Humans , Mycophenolic Acid/adverse effects , Young AdultABSTRACT
OBJECTIVES: This study aimed to determine whether a range of single-time-point ultrasound (US) measures of synovial disease and serologic characteristics were able to predict progression of US-defined erosive disease in patients with established rheumatoid arthritis (RA). MATERIALS AND METHODS: Forty patients were studied prospectively. At baseline, subjective US measures of bone damage and synovial disease, including grayscale and power Doppler (PD) scores pre- and post-Sonovue contrast, were obtained from one proximal inter-phalangeal or metacarpo-phalangeal joint per patient. After a minimum of 2 years, the same joints were scanned to obtain a new US erosion score. RESULTS: Follow-up US erosion scores were obtained in 25 joints. Progressive US determined that bone damage occurred in 12/25 joints, including four of eight treated with anti-tumor necrosis factor therapy. Baseline erosion scores were significantly higher in joints that did not show progressive bone damage in the entire cohort (p = 0.05, n = 25) and a subgroup treated with disease-modifying anti-rheumatic drugs (p = 0.015, n = 17). There were no other significant differences in baseline US or serologic scores between joints that developed progressive damage and those that did not. CONCLUSIONS: The majority of single-time-point US measures of synovial disease were not able to identify metacarpo-phalangeal or inter-phalangeal joint destined to develop progressive US-determined bone damage in patients with established RA. This may reflect the use of single-time-point measures, insensitivity of the US erosion score, and the long duration of RA disease in this study.
Subject(s)
Arthritis, Rheumatoid/diagnostic imaging , Finger Joint/diagnostic imaging , Ultrasonography, Doppler/methods , Adult , Aged , Aged, 80 and over , Arthritis, Rheumatoid/pathology , Contrast Media , Disease Progression , Female , Finger Joint/pathology , Follow-Up Studies , Humans , Male , Middle Aged , Phospholipids , Predictive Value of Tests , Prospective Studies , Sulfur HexafluorideABSTRACT
A hallmark of systemic lupus erythematosus (SLE) is the production of autoantibodies directed against intracellular antigens. Antibodies to double stranded DNA (dsDNA) are most closely associated with the clinical manifestations of the condition and appear to have a direct role in pathogenesis. On the contrary, the relationship between disease activity in SLE and anti-extractable nuclear antigen (ENA) antibodies has not been well demonstrated. Despite this, commercial assays for the quantification of anti-ENA antibodies are now widely available, although their usefulness in clinical practice is not known. The aim of this study was to investigate whether there is an association between disease activity in SLE and concentrations of individual anti-ENA antibodies. A prospective 2-year study of 45 patients with SLE, known to be positive for at least one anti-ENA antibody, was performed. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI). Anti-ENA antibodies were quantified using a commercial antibody detection system. A total of 45 patients were studied over a 2-year period (median number of assessments 5, range 2-9). Of them 29 patients were positive for Ro, 8 for La, 9 for Sm and 27 for RNP antibodies. In the population as a whole, there was a weak relationship between peak SLEDAI score and anti-Sm concentration (r = 0.57, NS), but no relation with the other anti-ENA antibodies. In a small number of patients, there appeared to be either a positive (Ro, Sm) or negative (La, Sm, RNP) association between ENA antibody concentration and disease activity over time; however, this was not apparent for the majority of individuals. These results show that in SLE, clinically significant changes in disease activity do not correlate well with concentrations of anti-ENA antibodies, either within the population as a whole or on an individual basis. Repeated quantitative measurement of anti-ENA antibodies does not therefore appear to provide useful additional information in assessing disease activity in SLE. The widespread application of commercial quantitative assays to routine clinical practice is not recommended.
Subject(s)
Antibodies, Antinuclear/blood , Lupus Erythematosus, Systemic/blood , Severity of Illness Index , Adult , Aged , Biomarkers/blood , Female , Humans , Male , Middle Aged , Prospective StudiesABSTRACT
OBJECTIVES: To investigate the practicality and tolerability of high-dose intramuscular (i.m.) vitamin D2 or oral vitamin D3 replacement in vitamin D-insufficient patients, and to evaluate the biochemical efficacy of each formulation. METHODS: Sixty-nine patients with vitamin D insufficiency [25-hydroxyvitamin D (25(OH)D) <40 nmol/L] were recruited from the Rheumatology Outpatient Department of St George's Hospital, London. In study 1, 50 patients received 300 000 IU i.m. vitamin D2 (ergocalciferol). In study 2, 19 patients received 300 000 IU oral vitamin D3 (cholecalciferol) under observation. Biochemical response was measured at baseline, and at 12 and 24 weeks. RESULTS: Bolus i.m. vitamin D2 or oral vitamin D3 was well tolerated. The change from baseline in serum 25(OH)D was significantly greater at 6 and 12 weeks in study 2 (p<0.0001 and <0.0001, respectively). In study 1, a modest increase in mean serum 25(OH)D at 6, 12, and 24 weeks was observed but no patients achieved a serum 25(OH)D concentration > or = 50 nmol/L. PTH remained elevated in 42% of patients with secondary hyperparathyroidism at 12 weeks. In study 2, 100% and 89% of patients had serum 25(OH)D>50 nmol/L at 6 and 12 weeks, respectively. All patients with elevated baseline PTH were fully suppressed at 12 weeks. No cases of hypercalcaemia were observed in either group. CONCLUSION: The 300 000-IU bolus of vitamin D2 or D3 was practical, well tolerated, and safe. Vitamin D3 had greater potency than equimolar vitamin D2, with a higher, sustained serum 25(OH)D response and efficacious PTH suppression. To adequately treat vitamin D insufficiency we would recommend administering 300,000 IU oral vitamin D3 approximately three times per year.
Subject(s)
Calcifediol/deficiency , Cholecalciferol/therapeutic use , Ergocalciferols/therapeutic use , Vitamin D Deficiency/drug therapy , Administration, Oral , Adult , Aged , Aged, 80 and over , Calcifediol/blood , Cholecalciferol/administration & dosage , Ergocalciferols/administration & dosage , Female , Humans , Hyperthyroidism/blood , Hyperthyroidism/complications , Hyperthyroidism/drug therapy , Injections, Intramuscular , Male , Middle Aged , Parathyroid Hormone/blood , Treatment Outcome , Vitamin D Deficiency/blood , Vitamin D Deficiency/etiology , Young AdultABSTRACT
The prevalence of cocaine use is rising worldwide, with a resultant rise in associated pathology. Regular nasal use can cause cocaine-induced midline destructive lesions (CIMDL), which can be difficult to distinguish from ear, nose, and throat (ENT)-limited Wegener's granulomatosis (WG). Two cocaine users presented with mid-facial pain, epistaxis, and systemic symptoms. Both had nasal septal perforation, necrosis of sinus mucosa, and positive anti-neutrophil cytoplasmic antibodies (ANCA). Histology was inconclusive and treatment with immunosuppressive drugs was commenced. The first patient continued to use cocaine initially, with improvement in her symptoms only on high doses of steroid. Later she stopped cocaine and this plus a switch from cyclophosphamide to mycophenolate mofetil resulted in successful symptom resolution and steroid withdrawal. The second patient denied cocaine use but having only partially responded to high-dose prednisolone and methotrexate, she admitted continued cocaine use and was lost to follow-up. Evaluation of a patient with destructive lesions of the mid-face should include enquiry about intranasal use of cocaine. Localized ENT involvement, inconsistent ANCA pattern, and atypical biopsy findings for WG should be recognized as features of CIMDL. Although cessation of cocaine use is crucial, there may be a role for immunosuppression.
Subject(s)
Cocaine-Related Disorders/diagnosis , Granulomatosis with Polyangiitis/diagnosis , Adult , Cocaine-Related Disorders/therapy , Diagnosis, Differential , Female , Granuloma, Lethal Midline/diagnosis , Humans , Immunosuppression TherapyABSTRACT
BACKGROUND: Basic competency in musculoskeletal medicine is essential for many specialties being particularly relevant to primary care. AIM: The purpose of this study was to objectively assess the adequacy of musculoskeletal education at multiple levels of medical training from undergraduate level to primary care. METHODS: A previously validated musculoskeletal examination was administered to 303 volunteers consisting of medical students, orthopaedic specialist registrars, general practice trainees and general practitioners. RESULTS: Forty (71%) general practitioners and 74 (71.8%) general practice trainees failed to obtain the passing score of 70. Sixty-three (87.5%) medical students who had completed an intensive 1-week long course in musculoskeletal medicine failed the examination. The pass rate improved significantly for general practitioners who had completed a postgraduate rotation in musculoskeletal medicine (47.8 vs 18.1%, P < 0.01). CONCLUSIONS: These findings suggest that training in musculoskeletal medicine is inadequate at multiple levels of medical education with reform urgently required.
Subject(s)
Education, Medical, Continuing/standards , Education, Medical, Undergraduate/standards , Musculoskeletal Diseases/diagnosis , Physicians, Family/education , Adult , Clinical Competence , Educational Measurement , Humans , Ireland , Musculoskeletal Diseases/therapy , Physical ExaminationABSTRACT
OBJECTIVES: Ultrasound (US) provides measurements of synovial morphology and vascularity. However, on an individual joint basis in RA, US measures do not relate well to clinical signs. This study investigates the relationship between composite US measures and the 28-joint disease activity score (DAS28), its components and acute phase markers in adult RA. METHODS: RA synovial disease activity was recorded in 50 patients by: (i) the DAS28 score; (ii) ESR and CRP; and (iii) US using Grey scale (GS) and power Doppler (PD) measures of PIP and MCP joints to derive composite US scores based on abnormal counts and severity. A total of 25 control subjects were studied to define normal US appearances. The relation between each measure of synovial disease was determined by Spearman correlation analysis. RESULTS: There was a significant relation between the DAS28 and the GS joint count (GSJC, Spearman's r = 0.4; P = 0.004) and severity score (GSJS, r = 0.34; P = 0.016) and the PD joint count (PDJC, r = 0.32; P = 0.028). There was a significant relation between the ESR and PDJC (r = 0.37; P = 0.007) and PD joint severity score (PDJS, r = 0.38; P = 0.006) and between the CRP and PDJS (r = 0.29; P = 0.04). The remaining components of the DAS28 related poorly to all US measures, except the tender joint count, which related significantly to the GS but not the PD measures. CONCLUSIONS: Composite US markers of synovial disease relate significantly to the DAS28 score and ESR/CRP in adult RA, but not as well with individual clinical joint counts and the patient's global assessment.
Subject(s)
Arthritis, Rheumatoid/diagnostic imaging , Adult , Aged , Aged, 80 and over , Arthritis, Rheumatoid/diagnosis , Biomarkers/blood , Blood Sedimentation , C-Reactive Protein/analysis , Female , Finger Joint/diagnostic imaging , Humans , Hypertrophy/diagnosis , Hypertrophy/diagnostic imaging , Male , Metacarpophalangeal Joint/diagnostic imaging , Middle Aged , Severity of Illness Index , Synovial Membrane/diagnostic imaging , Synovial Membrane/pathology , Synovitis/diagnosis , Synovitis/diagnostic imaging , UltrasonographyABSTRACT
OBJECTIVES: Synovitis in rheumatoid arthritis (RA) is assessed clinically by the presence of joint tenderness and swelling. Synovial thickening and increased vascularity may also be detected by high-resolution ultrasonography (US) and power Doppler (PD). This study investigated the relationship between clinical and sonographic features of synovial disease utilizing US, PD and the contrast agent Sono-Vue. METHODS: Forty RA patients were recruited. One proximal inter-phalangeal or metacarpophalangeal joint was selected per patient, as being unambiguously either: swollen and tender, just swollen, just tender or neither swollen nor tender (Nil). Ten joints were selected per clinical group. On US, the mean synovial thickness was measured and synovial hypertrophy and erosions were graded subjectively. Synovial vascularity demonstrated by PD was scored subjectively pre- and post-contrast. RESULTS: All grades of synovial vascularity were found in each clinical group including the Nil group. There were significant differences between the four clinical groups for both synovial hypertrophy (P = 0.024) and PD scores pre- (P = 0.022) and post- (P = 0.039) contrast. Tender-only joints showed significantly less vascularity than other groups. Post-contrast, the median PD scores increased in all but the Nil group, in some cases from the normal to abnormal range. CONCLUSION: Synovitis demonstrated by US and PD is not predicted by patterns of disease as described by joint swelling and tenderness despite unambiguous selection of joints. Synovial vascularity was the least in tender-only joints and was heterogeneous in all other groups, including Nil joints. These findings question the reliability of traditional clinical signs in RA synovitis assessment.
Subject(s)
Arthritis, Rheumatoid/complications , Synovitis/diagnostic imaging , Adult , Aged , Aged, 80 and over , Contrast Media , Female , Humans , Male , Microbubbles , Middle Aged , Phospholipids , Physical Examination , Prospective Studies , Severity of Illness Index , Sulfur Hexafluoride , Synovitis/diagnosis , Synovitis/etiology , UltrasonographyABSTRACT
The rhizosphere is the site of intense interactions between plant, bacterial, and fungal partners. In plant-bacterial interactions, signal molecules exuded by the plant affect both primary initiation and subsequent behavior of the bacteria in complex beneficial associations such as biocontrol. However, despite this general acceptance that plant-root exudates have an effect on the resident bacterial populations, very little is still known about the influence of these signals on bacterial gene expression and the roles of genes found to have altered expression in plant-microbial interactions. Analysis of the rhizospheric communities incorporating both established techniques, and recently developed "omic technologies" can now facilitate investigations into the molecular basis underpinning the establishment of beneficial plant-microbial interactomes in the rhizosphere. The understanding of these signaling processes, and the functions they regulate, is fundamental to understanding the basis of beneficial microbial-plant interactions, to overcoming existing limitations, and to designing improved strategies for the development of novel Pseudomonas biocontrol strains.
Subject(s)
Bacterial Physiological Phenomena , Plants/microbiology , Genes, Reporter/genetics , Pest Control, Biological , Plants/genetics , ProteomicsABSTRACT
OBJECTIVE: To develop objective, isotonic, reliable and valid tests of upper (UL) and lower (LL) limb proximal muscle function for use in the management of idiopathic inflammatory myositis (IIM). METHODS: The '1 kg arm lift' test was devised to assess UL function and the '30 s chair stand' test was used for LL function. The tests were performed in 30 control subjects to determine short (24 h) and long (2 week) interval test-retest reliability. Thirty-two patients with IIM were assessed over a period of 2 yr. RESULTS: In the control group both tests showed excellent test-retest reliability; Spearman correlation >0.8 for both tests over both time intervals. Twenty-four of the 32 IIM patients remained in remission over a mean period of 20.7 months throughout which scores varied by <5 for the '1 kg arm lift' test and <3 for the '30 s chair stand' test from each patient's mean score. Eight patients relapsed with scores falling by >5 for the '1 kg arm lift' test and by >3 for the '30 s chair stand' test from the mean remission score in each case. Both UL and LL scores correlated inversely with serum creatinine kinase. CONCLUSION: Two isotonic tests of proximal muscle function are described. They exhibit excellent test-retest reliability and demonstrate construct validity in IIM. Both tests are responsive to changes in disease activity, offer physiological and practical advantages over existing tests of muscle function and are suitable for use in clinical practice.
Subject(s)
Muscle, Skeletal/physiopathology , Myositis/diagnosis , Severity of Illness Index , Adult , Aged , Arm/physiopathology , Biomarkers/blood , Creatine Kinase/blood , Female , Humans , Isotonic Contraction , Leg/physiopathology , Male , Middle Aged , Myositis/physiopathology , Myositis/therapy , Recurrence , Remission Induction , Reproducibility of Results , Treatment OutcomeABSTRACT
Hurling is a contact sport, associated with significant morbidity. We have identified specific hand injuries sustained by participants and quantified the functional and financial implications of these injuries. Over a 3-month period, all hand injuries seen in the fracture clinic of our regional trauma unit were studied prospectively. Of the 123 consecutive injuries, 41 (33%) were sustained during hurling matches. Metacarpal (47%) and proximal phalangeal (37%) fractures were the most frequent. Eight hurlers (20%) required surgical intervention. Only four (10%) of the injured players were wearing hand protection. The mean cost of injury to the player was pound 615. We suggest the introduction of the mandatory use of hand protection for hurling.
Subject(s)
Athletic Injuries/therapy , Hand Injuries/therapy , Adolescent , Adult , Athletic Injuries/economics , Athletic Injuries/epidemiology , Child , Cost of Illness , Female , Hand Injuries/economics , Hand Injuries/epidemiology , Humans , Ireland/epidemiology , Male , Middle AgedABSTRACT
Severe factor IX deficiency is an X-linked disorder which gives rise to spontaneous and often life-threatening bleeds. The major source of morbidity worldwide is recurrent haemarthroses, giving rise to joint destruction and deformity. However, the incidence of spontaneous haemarthroses has decreased since the advent of prophylactic home-based, on-demand, early replacement therapy. We present the case of a non-ambulant, 13-year-old boy from Chernobyl, who did not have access to this type of treatment, and whose deformity was managed using the Ilizarov external fixator. An external fixator was applied under general anaesthetic in theatre. Haemostasis was achieved by maintaining his FIX levels at 1.0 IU mL(-1) pre- and post-operatively. Three months later, the fixed flexion deformity had been reduced from 50 to 5 degrees. Four months postsurgery, this boy was walking freely without pain. There was no peri- or post-operative bleeding or joint swelling.
Subject(s)
Contracture/surgery , Hemophilia B/complications , Ilizarov Technique , Knee Joint/surgery , Adolescent , Contracture/etiology , External Fixators , Follow-Up Studies , Hemarthrosis/complications , Humans , MaleABSTRACT
OBJECTIVE: To study the safety and efficacy of infliximab plus leflunomide combination therapy in adult rheumatoid arthritis (RA). METHODS: Twenty patients with active RA received leflunomide 100 mg for 3 days followed by 20 mg daily for 32 weeks. At week 2 all patients started infliximab 3 mg/kg, and received a further four infusions at weeks 4, 8, 16 and 24. RESULTS: Adverse events led to 11 patients being withdrawn before the end of the study. The commonest adverse event was pruritus associated with an eczematous rash. Other serious reactions included infliximab infusion reactions in four patients and Stevens-Johnson syndrome in one. There was no relationship between the serum concentration of A77 1726, the active metabolite of leflunomide, and adverse events. The mean Disease Activity Score (DAS28) fell from 7.18 at week 0 to 5.18 (P<0.0001, paired t-test) at week 4 and remained between 3.85 and 4.85 up to week 32. In those patients remaining on treatment, more than 80% achieved an ACR20 response from week 8 to week 28, and up to 46% achieved an ACR70 response. CONCLUSION: Infliximab plus leflunomide combination therapy appears to be highly efficacious in the treatment of adult RA. However, widespread use may be limited by adverse events, which were common and in some cases severe.
Subject(s)
Antibodies, Monoclonal/adverse effects , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Immunosuppressive Agents/adverse effects , Isoxazoles/adverse effects , Adult , Aged , Anaphylaxis/etiology , Antibodies, Monoclonal/administration & dosage , Antirheumatic Agents/administration & dosage , Arthritis, Rheumatoid/immunology , Autoantibodies/blood , Combined Modality Therapy , Diarrhea/etiology , Drug Eruptions/etiology , Female , Humans , Hypertension/chemically induced , Immunosuppressive Agents/administration & dosage , Infections/etiology , Infliximab , Isoxazoles/administration & dosage , Leflunomide , Liver/enzymology , Male , Middle Aged , Oral Ulcer/chemically induced , Pilot Projects , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/immunologyABSTRACT
BACKGROUND: Systemic ischaemia-reperfusion (IR) injury is in part an oxidant injury mediated by neutrophils. Diethylmaleate (DEM), an intracellular pro-oxidant agent, has been shown to alleviate neutrophil-mediated tissue injury. The aim of this study was to evaluate whether DEM could have a protective effect on neutrophil-mediated lung injury in an animal model of lower-torso IR. METHODS: Sprague-Dawley rats (seven per group) were randomized into three groups. The control group underwent midline laparotomy only; the IR group underwent laparotomy and clamping of the infrarenal abdominal aorta for 30 min followed by 2 h of reperfusion; and the third group was pretreated with DEM 6 mmol/kg intraperitoneally 1 h before the IR insult. RESULTS: IR resulted in a significant increase in both microvascular leakage and pulmonary neutrophil infiltration as measured by bronchoalveolar lavage protein concentration and pulmonary myeloperoxidase activity respectively. Pretreatment with DEM significantly attenuated both microvascular leakage and neutrophil infiltration. CONCLUSION: Preconditioning with DEM protected against IR-induced lung injury. This protective effect raises the possibility of using pro-oxidants to prevent inflammatory injury.