'Sink or swim': an evaluation of the clinical characteristics of individuals with high bone mass.

SUMMARY: High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI). HBM cases may harbour an underlying genetic disorder. INTRODUCTION: High bone mineral density is a sporadic incidental finding on routine DXA scanning of apparently asymptomatic individuals. Such individuals may have an underlying skeletal dysplasia, as seen in LRP5 mutations. We aimed to characterize unexplained HBM and determine the potential for an underlying skeletal dysplasia. METHODS: Two hundred fifty-eight individuals with unexplained HBM (defined as L1 Z-score ≥ +3.2 plus total hip Z-score ≥ +1.2, or total hip Z-score ≥ +3.2) were recruited from 15 UK centres, by screening 335,115 DXA scans. Unexplained HBM affected 0.181% of DXA scans. Next 236 relatives were recruited of whom 94 (41%) had HBM (defined as L1 Z-score + total hip Z-score ≥ +3.2). Fifty-eight spouses were also recruited together with the unaffected relatives as controls. Phenotypes of cases and controls, obtained from clinical assessment, were compared using random-effects linear and logistic regression models, clustered by family, adjusted for confounders, including age and sex. RESULTS: Individuals with unexplained HBM had an excess of sinking when swimming (7.11 [3.65, 13.84], p < 0.001; adjusted odds ratio with 95% confidence interval shown), mandible enlargement (4.16 [2.34, 7.39], p < 0.001), extra bone at tendon/ligament insertions (2.07 [1.13, 3.78], p = 0.018) and broad frame (3.55 [2.12, 5.95], p < 0.001). HBM cases also had a larger shoe size (mean difference 0.4 [0.1, 0.7] UK sizes, p = 0.009) and increased BMI (mean difference 2.2 [1.3, 3.1] kg/m(2), p < 0.001). CONCLUSION: Individuals with unexplained HBM have an excess of clinical characteristics associated with skeletal dysplasia and their relatives are commonly affected, suggesting many may harbour an underlying genetic disorder affecting bone mass.

Malignancy in scleroderma patients from south west England: a population-based cohort study.

The pathophysiological relationship between scleroderma and malignancy remains poorly understood. Although some previous studies have demonstrated an increased malignancy risk in patients with scleroderma, others have been inconclusive. We aimed to determine if patients with scleroderma had an increased risk of malignancy compared to an age- and sex-matched local South West England population, and if there were any important differences between scleroderma patients with and without malignancy. Methods of this study are as follows. Notes were obtained on all local scleroderma patients (n = 68) locally, and those diagnosed with malignancy verified by contacting each patient's general practitioner. Expected malignancy figures were obtained from age- and sex-stratified regional prevalence data provided by the South West Cancer Intelligence Service registry. Among the patients, 22.1% with scleroderma were identified with concurrent malignancy. Affected sites were of the breast (n = 5), haematological system (n = 5), skin (n = 4), and unknown primary (n = 1). Overall, malignancy risk was found to be increased in scleroderma (RR = 3.15, 95% CI 1.77-5.20, p = 0.01). In particular, this risk was the highest for haematological malignancies (RR = 18.5, 95% CI 6-43, p = 0.03), especially for non-Hodgkin's lymphoma (RR = 25.8, 95% CI 5-75, p = 0.10). The majority of patients (86.7%) developed malignancy after the onset of scleroderma (mean = 6.9 years). Age of >70 and patients with limited scleroderma were significant risk factors for a patient with scleroderma to have a concurrent malignancy; however, no increased risk was found in patients with any particular pattern of organ involvement, cytotoxic usage or serology. To conclude, in this small patient cohort, we have found that scleroderma is associated with an increased risk of malignancy. This risk is statistically significant in patients with limited scleroderma. Patients who are elderly and those with limited disease should be closely scrutinized at follow-up appointments.

A comparison of paediatric soccer, gaelic football and rugby injuries presenting to an emergency department in Ireland.

OBJECTIVES: Children presenting with sport related injuries (SRIs) as a result of soccer, rugby and gaelic football are frequently seen in an emergency medicine (EM) setting in Ireland. A comparison of the demographics of injuries in these three sports has however not previously been performed. The purpose of this study was to provide up-to-date data on the nature of these SRIs. METHOD: Data was collected retrospectively on all children (<17 years of age), injured in these three sports, presenting to an emergency medicine department over 6 months, and was entered into a database for analysis. RESULTS: Retrospective analysis was performed on 23,000 charts, and 409 SRIs were identified over a 6-month period. None of the children reported using any form of protective gear, and 27% reported a previous presentation to the emergency department with a SRI. Most injuries were as a result of soccer (56%), with 24% occurring in gaelic football, and 20% occurring in rugby. The predominant mechanism of injury was different in each sport, in soccer-falls (38%), in gaelic football-collisions with objects (balls) (37%), and in rugby-collision with persons (55%). Although the predominant type of injury in soccer and gaelic football was a fracture, accounting for 50% and 42% of injuries, respectively, in rugby however, skin/soft tissue injuries presented more commonly, accounting for 44% of injuries. When the general site of injury was investigated, the upper limb accounted for the majority of SRIs in each sport. In the management of SRIs, oral analgesics were prescribed in 50%, however, it was observed that no use was made of topical, intramuscular or rectal analgesic routes of administration. In addition it was observed that RICE/general injury advice was given in only 27%, physiotherapy was requested in 2%, and no injury prevention advice was given to any child. Overall, 8% required admission. CONCLUSIONS: The data provided from this study may raise awareness of the nature of SRIs affecting children in each of these three sports, and may be useful in formulating much needed injury prevention strategies.

The outcome of direct current cardioversion (DCC) for the treatment of atrial fibrillation (AF) in a district general hospital in Ireland.

BACKGROUND: Direct current cardioversion (DCC) is a method to control persistent AF, to facilitate a reduction in stroke risk. Although this is a frequently performed procedure, there are no available published data regarding its outcome in an Irish setting. AIMS: To determine the short- and long-term outcome of DCC, factors predicting a successful outcome, and its safety. METHODS: Data relating to each DCC were collected retrospectively from patient notes over a 6.3 year-period, and subsequently entered into a Microsoft Access database before subsequent statistical analysis. RESULTS: Forty-five consecutive unselected patients were identified, in which 59 DCCs were performed. Sinus rhythm (SR) was achieved immediately after DCC in 54/59 (91%) patients. There was a significant positive correlation between patient body weight and the energy level required to achieve SR (p=0.0001). No thromboembolic complications were noted. After a mean follow-up time of 12 +/- 13.7months, 30/45 (67%) had maintained SR. After univariate analysis, a number of important factors predictive of maintenance of SR at follow-up were identified. CONCLUSION: DCC was found to be an effective method for short- and long-term control of AF, without thromboembolic complications, and patients with a favourable long-term outcome after DCC could conceivably be predicted on the basis of a methodical history, careful examination, simple investigations and pharmacological variables.

LST1 and NCR3 expression in autoimmune inflammation and in response to IFN-gamma, LPS and microbial infection.

Many genes in the central region of the major histocompatibility complex (MHC) encode proteins involved in immune and inflammatory responses. In this study, we have further characterized two genes in the MHC class IV region, leucocyte-specific transcript (LST) 1 and natural cytotoxicity-triggering receptor 3 (NCR3) (also known as 1C7 and natural killer (NK)p30). The specific function of LST1 is not known, although expression analysis and functional data suggest an immunomodulatory role. The LST1 gene undergoes extensive alternative splicing, giving rise to both membrane-bound (encoded by exon 3) and soluble isoforms. The NCR3 protein is involved in NK-mediated cytotoxicity and plays a role in NK/dendritic cell crosstalk. Expression of these genes was examined, by real-time reverse transcriptase-polymerase chain reaction, in autoimmune-induced inflammation, specifically rheumatoid-arthritis-affected blood and synovium, and in response to stimulation with inflammatory mediators and bacterial agents. The expression of LST1, specifically splice variants encoding soluble isoforms and NCR3, was increased in rheumatoid-arthritis-affected blood and synovium and was associated with more severe inflammation in the synovium. Furthermore, both genes were significantly up-regulated in response to lipopolysaccharide, interferon (IFN)-gamma and bacterial infection. These findings suggest that NCR3 and soluble isoforms of LST1 may play a role in inflammatory and infectious diseases.