Patients with tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) are hypersensitive to Toll-like receptor 9 stimulation.

Tumour necrosis factor receptor-associated periodic syndrome (TRAPS) is a hereditary autoinflammatory disorder characterized by recurrent episodes of fever and inflammation. It is associated with autosomal dominant mutations in TNFRSF1A, which encodes tumour necrosis factor receptor 1 (TNF-R1). Our aim was to understand the influence of TRAPS mutations on the response to stimulation of the pattern recognition Toll-like receptor (TLR)-9. Peripheral blood mononuclear cells (PBMCs) and serum were isolated from TRAPS patients and healthy controls: serum levels of 15 proinflammatory cytokines were measured to assess the initial inflammatory status. Interleukin (IL)-1ß, IL-6, IL-8, IL-17, IL-22, tumour necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), interferon (IFN)-γ, monocyte chemoattractant protein 1 (MCP-1) and transforming growth factor (TGF)-ß were significantly elevated in TRAPS patients' sera, consistent with constitutive inflammation. Stimulation of PBMCs with TLR-9 ligand (ODN2006) triggered significantly greater up-regulation of proinflammatory signalling intermediates [TNF receptor-associated factor (TRAF 3), IL-1 receptor-associated kinase-like 2 (IRAK2), Toll interacting protein (TOLLIP), TRAF6, phosphorylated transforming growth factor-ß-activated kinase 1 (pTAK), transforming growth factor-ß-activated kinase-binding protein 2 (TAB2), phosphorylated TAK 2 (pTAB2), IFN-regulatory factor 7 (IRF7), receptor interacting protein (RIP), nuclear factor kappa B (NF-κB) p65, phosphorylated NF-κB p65 (pNF-κB p65) and mitogen-activated protein kinase kinase (MEK1/2)] in TRAPS patients' PBMCs. This up-regulation of proinflammatory signalling intermediates and raised serum cytokines occurred despite concurrent anakinra treatment and no overt clinical symptoms at time of sampling. These novel findings further demonstrate the wide-ranging nature of the dysregulation of innate immune responses underlying the pathology of TRAPS and highlights the need for novel pathway-specific therapeutic treatments for this disease.

Sudden collapses in the heat in patients on angiotensin type 2 receptor blockers.

CONTEXT: A clinical case report is presented of some patients taking angiotensin type 2 receptor blockers (AT2RB) who collapsed without warning whilst being active outdoors in the heat. ISSUES: It is not possible to recognise hypotension due to the heat by testing in a controlled environment such as a doctor's office. Many people taking AT2RBs may be thus misdiagnosed and inappropriately treated. LESSONS LEARNED: Sudden collapse in a patient on AT2RB who is active in the heat should alert the physician to the possible cause of extreme sensitivity to low-grade volume depletion.

Publication of surgeon specific outcome data: a review of implementation, controversies and the potential impact on surgical training.

Government-mandated publication of named surgeon-specific outcome data (SSD) has recently been introduced across nine surgical speciality areas in England. This move is the first time that such national data has been released in any country, and it promises to provide a significant advancement in health service transparency. Data is derived from nine preexisting national surgical audit databases. However, eight of these were not originally designed for this purpose, and there is considerable controversy surrounding data quality, risk adjustment, patient use and interpretation, and surgeons' subsequent case selection. Concerns also surround the degree to which these results truly reflect the individual consultant, or the wider hospital team and accompanying resources. The potential impact on surgical training has largely been overlooked. This paper investigated the background to SSD publication and controversies surrounding this, the potential impact on surgical training and the response to these concerns from medical and surgical leaders. As SSD collection continues to be refined, the most appropriate outcomes measurements need to be established, and risk adjustment requires ongoing improvement and validation. Prospective evaluation of changes in surgical training should be undertaken, as any degradation of will have both short and long-term consequences for patients and surgeons alike. It is important that the literature supporting the safety of supervised trainee practice is also promoted in order to counterbalance any potential concerns that might detract from trainee operating opportunities. Finally, it is important that outcomes data is communicated to patients in the most meaningful way in order to facilitate their understanding and interpretation given the complexities of the data and analysis involved.

Aspiration complicating bronchopulmonary dysplasia.

The purpose of this study was to study the relationship of aspiration with ongoing respiratory difficulties in infants with bronchopulmonary dysplasia (BPD). Twelve infants with BPD were identified out of 314 children who had flexible bronchoscopy between 1987 and 1990; 11 of 12 had bronchoalveolar lavage (BAL). The lipid index (LI) was used to quantify the degree of lipid-laden macrophages in the BAL fluid as a marker of aspiration. The age range at the time of bronchoscopy was 3 months to 5 years. The LI was considered positive in 6 of 11 subjects. A pH probe study was done on seven subjects with concordant findings in five. Other findings included dynamic or structural airway abnormalities in 10 of the 12 subjects. These data suggest that aspiration frequently is associated with BPD in addition to the previously recognized dynamic and structural airway problems. The predisposition to gastroesophageal reflux and laryngeal injury probably accounts for the increased aspiration risk in children with BPD.

Association of MS Pi phenotype with airway hyperresponsiveness.

Asthmatic families (AFs) and normal families (NFs) were studied to determine the relationship between bronchial hyperresponsiveness and alpha 1-antitrypsin protease inhibitor phenotype. We studied IgE levels, skin test scores, and methacholine sensitivity. In both the AF and NF groups, the subjects with the MS phenotype had significantly greater methacholine-induced bronchial hyperresponsiveness sensitivity than the MM and MZ subjects. These findings suggest that the S allele may be associated with bronchial hyperresponsiveness.

Longitudinal changes in bronchial hyperresponsiveness in asthmatic and previously asthmatic children.

To determine if nonspecific bronchial hyperresponsiveness is present to the same degree in previously asthmatic children compared with currently asthmatic children, a longitudinal study was conducted. On the basis of a standardized respiratory questionnaire, 139 children from asthmatic families, between the ages of 6 and 21 years, were identified. Subjects had skin tests, a serum IgE level, and a methacholine challenge test. IgE and skin tests demonstrated atopy in both the previously and currently asthmatic children, which persisted over time. Bronchial hyperresponsiveness within the asthmatic children was not significantly different between visits. Previously asthmatic children did have significantly decreased airway hyperresponsiveness over time. Age did not affect the results of the bronchial hyperresponsiveness in the currently asthmatic children. Currently asthmatic children, however, were significantly more atopic when compared with previously asthmatic children at their initial evaluation. Currently asthmatic children were also more bronchial responsive and remained so over time. Bronchial hyperresponsiveness is persistent in children with current asthma symptoms.

Investigation of the kinetics of anaerobic metabolism by analysis of the performance of elite sprinters.

The principal motivation for the present work was the study of the kinetics of anaerobic metabolism. A new mathematical model of the bioenergetics of sprinting, incorporating a three-equation representation of anaerobic metabolism, is developed. Results computed using the model are compared with measured data from the mens' finals of the 100m event at the 1987 World Championships. The computed results closely predict the overall average performance of the competitors over the course of the entire race. Further calculations show the three-equation model of anaerobic metabolism to be a significant improvement over the previous one-equation model. Representative values of time constants that govern the rate of anaerobic energy release have been determined for elite male athletes. For phosphocreatine utilisation, values for lambda(2)=0. 20s(-1) and psi(2)=3.0s(-1) are consistent with data previously reported in the literature. New values of lambda(3)=0.033s(-1) and psi(3)=0.34s(-1) are proposed as offering an improved representation of the kinetics of oxygen-independent glycolysis. For the first time, tentative values for the time constants of ATP utilisation, lambda(1)=0.9s(-1) and psi(1)=20s(-1), are suggested. The maximum powers developed during sprinting by oxygen-independent glycolysis, PCr utilisation and endogenous ATP utilisation were calculated as 34. 1, 30.1 and 16.6Wkg(-1), respectively, with an overall maximum anaerobic power of 51.6Wkg(-1). Sample calculations show the mathematical model can be used in principle to derive data on the kinetics of anaerobic metabolism of individual athletes.

A prospective randomised comparison of the dynamic hip screw and the gamma locking nail.

We made a randomised prospective comparison of the Dynamic Hip Screw and the Gamma locking nail for the internal fixation of 200 petrochanteric femoral fractures in elderly patients. There was less intraoperative blood loss and a lower rate of wound complications in the patients treated by the Gamma nail. They had, however, a high incidence of femoral shaft fracture which we relate in part to implant design. We do not recommend the use of the Gamma nail for these fractures.

Anterior midline or medial parapatellar incision for arthroplasty of the knee. A comparative study.

Early mobilisation after arthroplasty of the knee sometimes results in wound breakdown. The two commonly used incisions, the anterior midline and the medial parapatellar incisions, were compared in order to determine which had the best potential for wound healing. Study of the cleavage lines around the knee demonstrated that the medial parapatellar incision lies parallel to the lines, whilst the anterior midline incision lies perpendicular to them. In addition, the medial parapatellar wound was found to be subjected to significantly less tension during flexion; after arthroplasty it can be expected to heal faster and to be less liable to disruption during early mobilisation.

Total hip replacement in the renal transplant recipient.

Osteonecrosis of the femoral head is a severely disabling complication of steroid immunosuppression in renal transplant patients. We report 31 total hip arthroplasties in 21 renal transplant recipients with an average follow-up of six years. There were no problems with wound healing or infection despite full immunosuppression. Four hips developed symptomatic loosening but the other results were excellent, comparing well with other methods of treatment for osteonecrosis. Ten patients died during the follow-up period. Total hip replacement is a safe and effective treatment for transplant recipients and, in view of their limited life expectancy, should be considered at an early stage in their treatment.

Hypoplastic scaphoid--an unusual cause of carpal tunnel syndrome.

A case of median nerve compression within the carpal tunnel, secondary to hypoplasia of the carpal scaphoid and dysplasia of the distal radius, is described in a 15-year-old boy with Spondylo-epiphyseal dysplasia tarda. Hypoplastic carpal bones and a dysplastic distal radius may be a feature of Spondylo-epiphyseal dysplasias, but carpal tunnel syndrome has not been previously reported either in this condition or in association with hypoplasia of the scaphoid.

The Herbert screw for delayed and non-union of scaphoid fractures: a review of fifty cases.

The results of treatment using the Herbert screw in 50 consecutive patients with delayed or established non-union of the scaphoid are reported. 14% of these fractures failed to unite after operation and a further 20% required prolonged protection, uniting within six months. There were significant technical problems in 28% of operations. A bone graft was only used when there was significant collapse of the scaphoid (52%) and the cases without graft did just as well. Overall, the results do not support the view that this method of treatment is a significant advance over Russe grafting in terms of union rates, but confirm that it produces similar results without the need for prolonged immobilisation and without the need for bone grafting in almost half the cases, although there can be significant technical problems with the procedure.

A rare and serious consequence of a rat bite.

Contact with rat saliva or faeces can lead to infection with Streptobacillus moniliformis and the condition known as 'rat bite fever'. We report a case of septic arthritis of the hip due to this organism following a bite on the finger of a 14-year-old boy from a rat for sale in a pet shop. The case was successfully treated by arthrotomy, drainage and joint lavage followed by administration of penicillin. Septic arthritis of the hip due to S. moniliformis has not been previously described and this case highlights a possible danger of keeping rats as pets.

Local anesthesia for postoperative pain relief after foot surgery: a prospective clinical trial.

A prospective, randomized, controlled clinical trial was set up to test whether the addition of ankle block to general anesthesia was useful in providing postoperative pain relief following forefoot surgery. Forty feet (20 treatment, 20 control) were entered into the trial and all underwent bony operations on the first ray. Pain was assessed at fixed times following the operation using pain analog scales. Analgesic consumption and wound healing were also assessed. A significant difference was found between the pain scores in the two groups at the 6-hr stage, but there was no difference in any of the other assessments. It is concluded that ankle block is a useful addition to general anesthesia for this type of surgery.

Association of Surgeons in Training conference: Belfast 2014.

The Association of Surgeons in Training (ASiT) is a professional body and registered charity working to promote excellence in surgical training for the benefit of junior doctors and patients alike. ASiT is independent of the National Health Service (NHS), Surgical Royal Colleges, and specialty associations and represents trainees in all ten surgical specialties. ASiT was delighted to welcome all four surgical Royal College Presidents and over 650 delegates to Belfast for ASiT 2014. With a theme of Marginal Gains, the conference programme explored collaboration, simulation training and human factors, complimented by debates including the Shape of Training Review (ShOT), several focussed parallel sessions and ten subsidised pre-conference training courses. Almost £4000 was awarded by the incoming President, Mr Vimal Gokani, to delegates across more than 30 prizes for delegates who presented the highest scoring academic work from over 1200 submitted abstracts.

Disinfection of flexible fibre-optic endoscopes out-of-hours: confidential telephone survey of ENT units in England - 10 years on.

OBJECTIVE: To audit out-of-hours flexible endoscope disinfection practice in England and compare the findings with a previously published first audit cycle, with the 2005 ENT UK guidelines as the key intervention. METHODS: A telephone survey of the 104 ENT units in England was conducted out-of-hours, replicating the first cycle. The on-call clinician answered questions concerning access to flexible endoscopes, training, disinfection procedures and record keeping. Information regarding the clinician's trainee grade and their cross-covering duties was also acquired. Responses were compared to the first cycle results and published guidance. RESULTS: In total, 72 of the 104 units agreed to participate. The on-call clinician cleaned the flexible endoscope in 43 per cent of units. However, adequate training in disinfection only occurred in a minority of units (37 per cent), though this was an improvement from the first cycle (12 per cent). Furthermore, 27 per cent of units used an inadequate method of disinfection out-of-hours. One confounding factor may be the increase in cross-cover out-of-hours, with 68 per cent of respondents covering one or more other specialties. CONCLUSION: An overall moderate improvement in the safety of out-of-hours endoscopy in the past 10 years cannot obscure the urgent need for universal compliance with national guidelines.