Sarcoidosis complicating treatment with natalizumab for Crohn's disease.

Natalizumab is a humanised monoclonal antibody targeting the lymphocyte adhesion molecule a4 integrin, with proven efficacy in multiple sclerosis (MS) and Crohn's disease (CD). The development of sarcoidosis with extrapulmonary involvement is reported in two patients with refractory CD who had received maintenance therapy with natalizumab. This complication has not been previously reported. It is hypothesised that the effect of natalizumab in altering lymphocyte mucosal trafficking may underlie the development of sarcoidosis in these patients.

Accuracy of cell typing in nonsmall cell lung cancer by EBUS/EUS-FNA cytological samples.

Endoscopic ultrasound-guided transbronchial or transoesophageal lymph node aspiration is increasingly used as a method of diagnosing nonsmall cell carcinoma. Data validating the accuracy of cell typing of nonsmall cell carcinoma using these cytological samples has not been assessed. 23 samples were identified in Edinburgh, UK and a further 25 in Cambridge, UK, with matching histological samples. The morphological cell type, as assessed on the cytological preparations and cell blocks, was recorded and immunohistochemical staining was performed, where possible, as an adjunct. The final cell type, as assessed by morphology with or without immunohistochemistry, was correlated with that reported in the paired histological samples. Cell blocks with tumour were available in 39 out of 48 cases. The accuracy of cell typing when no cell block was available was four out of nine cases. This increased to 25 out of 39 when a cell block was available, increasing to 33 out of 39 with the addition of immunohistochemistry. The overall accuracy of classification was 37 out of 48 cases. Accurate cell typing of nonsmall cell carcinomas can be performed using endoscopically derived fine-needle aspirates. The importance of obtaining sufficient material for the production of cell blocks is critical in allowing optimal assessment.

Regulatory role for macrophage migration inhibitory factor in acute respiratory distress syndrome.

Migration inhibitory factor (MIF) is known to exert significant pro-inflammatory effects and has the potential to override the anti-inflammatory action of glucocorticoids. In this study we have identified significant quantities of MIF in the alveolar airspaces of patients with acute respiratory distress syndrome (ARDS). We show in alveolar cells from patients with ARDS that MIF augments pro-inflammatory cytokine secretion (TNF alpha and IL-8), anti-MIF significantly attenuates TNF alpha and IL-8 secretion and MIF overrides, in a concentration-related fashion, the anti-inflammatory effects of glucocorticoids. These findings suggest that MIF may act as a mediator sustaining the pulmonary inflammatory response in ARDS and that an anti-MIF strategy may represent a novel therapeutic approach in inflammatory diseases such as ARDS.

Catastrophic injuries in the Olympic styles of wrestling in Iran.

OBJECTIVES: In this study, a profile of direct catastrophic injuries in international styles of wrestling was developed, and the possible risk factors were described. DESIGN: Survey and retrospective review. SETTING: Catastrophic injuries that occurred in wrestling clubs in Iran from July 1998 to June 2005 were identified by contacting several sources. The cases were retrospectively reviewed. RESULTS: The injuries included were 29 direct injuries (12 fatalities, 11 non-fatal and 6 serious).The injury rate was 1.99 direct catastrophic injuries/100 000 wrestlers/year. The majority of direct injuries occurred during training sessions, with a trend towards more injuries in the low-weight and middle-weight classes and those who were competing at high performance and experience levels. The takedown position, especially for the attacking wrestler who faces a counterattack, was the most common activity at the time of injury. A list of risk factors was suggested, of which "performing the wrestling manoeuvre incorrectly", "inappropriate management of the injury", "lack of the coach supervision", "mat problems" and "lack of restraining the wrestlers in a precarious position" were the most common risk factors. CONCLUSIONS: Catastrophic wrestling injuries are rare and preventable. Coaches have an essential role in the prevention of these injuries.

A single ThinPrep slide may not be representative in all head and neck fine needle aspirate specimens.

OBJECTIVES: Ideally, head and neck aspiration should be performed by trained aspirators within the setting of a one-stop clinic, where smeared material is available for immediate assessment. However, this may not always be possible for practical reasons and the use of liquid-based techniques in head and neck cytology is increasing. Although liquid-based cytology has been extensively validated for use in gynaecological cytology, no studies have investigated whether or not a single ThinPrep slide is representative for head and neck aspirate specimens. We performed a prospective audit of head and neck fine needle aspiration specimens processed by the ThinPrep method to investigate whether a single ThinPrep slide was representative. METHODS: A prospective audit of 115 consecutive head and neck aspirates was carried out. A single ThinPrep slide was prepared and a diagnosis recorded. The remainder of the specimen was then spun down and prepared as a cell block. The ThinPrep and cell block diagnoses were compared. RESULTS: In 36 cases (31%), the cell block provided additional information that contributed to the diagnosis. In 14 (12%), the cell block was regarded as essential to the diagnosis. CONCLUSIONS: A single ThinPrep slide may not provide representative diagnostic material in all head and neck aspirates. This should be taken into consideration when contemplating the use of liquid-based methods for non-gynaecological cytology.

Orthopaedic training experience in the UK and Ireland: an analysis using the eLogbook.

The eLogbook is used to collect and collate the operative experience of every orthopaedic trainee in the UK and Ireland. We describe the project and discuss the national data now emerging on elective and trauma training.

ALK immunohistochemistry is highly sensitive and specific for the detection of ALK translocated lung adenocarcinomas: lessons from an audit of lung cancer molecular testing.

Background The approval of novel targeted treatments for epidermal growth factor receptor (EGFR)-positive and anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer has led to the increased requirement for mutation testing. Results We report our experience of ALK testing with immunohistochemistry (IHC) and fluorescence in-situ hybridisation (FISH) and present the prevalence of EGFR, Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) and ALK mutations. From January 2011 to May 2014, we found mutation rates of EGFR, KRAS and ALK to be 10.4% (67/643), 35.8% (86/240) and 2.3% (7/304), respectively. ALK-rearrangements were found to be associated with never smokers (p < 0.001) and younger patients (≤ 50 years old) (p < 0.001). ALK IHC protein expression in tumour cells is 100% sensitive (7 IHC+/7 FISH+) and 96.6% specific (113 IHC-/117 FISH-) for ALK-rearrangements by FISH. ALK-rearranged tumours were wildtype for EGFR and KRAS. Conclusion Our findings support the use of ALK protein expression and KRAS mutation testing as part of the molecular diagnostic algorithm for lung adenocarcinomas.

Hemodynamic effects of pneumonia. II. Expansion of plasma volume.

Previous work has demonstrated that approximately one-third of patients with pneumonia have a hypodynamic circulatory response. This response is characterized by an abnormally wide arteriovenous oxygen difference, a low cardiac output, increased peripheral resistance, and an increased hematocrit. This state was found to abate in convalescence. In an attempt to elucidate the pathogenesis of this hypodynamic state, nine additional patients were studied hemodynamically during the acute phase of pneumonia before and during acute expansion of blood volume by low molecular weight dextran (seven patients) or normal saline (two patients). Five patients were restudied before and during acute blood volume expansion in convalescence. Three patients with pneumonia had a normal arteriovenous oxygen difference (< 5.5 vol%), and six patients were hypodynamic in that their arteriovenous oxygen differences were greater than 5.5 vol%. With expansion of blood volume in the acute phase of pneumonia, all patients showed an increase in cardiac output, a decrease in arteriovenous oxygen difference, and a decrease in peripheral vascular resistance; however, the percentage change in the hypodynamic patients was not as great as occurred in the patients with normal hemodynamics nor as great as occurred when restudied in convalescence. Likewise, all patients had a normal or near normal hemodynamic profile in convalescence. In addition, ventricular function in the acute phase of pneumonia was depressed. The findings suggest that the hypodynamic state associated with acute pneumonia is due to depressed myocardial contractility to which relative hypovolemia may contribute.

Endobronchial ultrasound-guided fine-needle aspiration and liquid-based thin-layer cytology.

BACKGROUND: Optimal management of patients with lung cancer requires accurate cell typing of tumours and staging at the time of diagnosis. Endobronchial ultrasound-guided lymph node aspiration as a method of diagnosing and staging lung cancer is a relatively new technique. AIM: To report the use of liquid-based-thin-layer cytology for the processing and reporting of these specimens. METHODS: The specimens obtained from 80 patients were processed using the ThinPrep system, with the remainder of the samples being processed as a cell block. RESULTS: 40 of the 81 procedures yielded malignant cells (30 non-small cell carcinoma, 8 small-cell carcinoma and 2 combined small-cell carcinoma/non-small-cell carcinoma). The cell blocks were found to contain sufficient material to allow the immunohistochemical characterisation of tumour cells with a range of antibodies. CONCLUSION: The use of liquid-based-thin-layer cytological techniques provides high-quality specimens for diagnostic purposes. When used in conjunction with cell blocks, sufficient material may be obtained to allow immunohistochemical studies to confirm the tumour cell type. Given the current move towards centralisation of pathology services, this approach gives the pathologist high-quality specimens without the need for direct onsite support at the time of the procedure.

Death in the New Town: Edinburgh's hidden story of stonemasons' silicosis.

The building of the Edinburgh New Town, from the mid-18th to the mid-19th centuries, was a major advance in harmonious and elegant town planning. However, there is anecdotal evidence that it led to the occurrence of an epidemic of silicosis/tuberculosis among the stonemasons. We have reviewed contemporary accounts of the episode and early records of the understanding of silicosis. We have also studied the lung of a contemporary stonemason, preserved in the museum of the Royal College of Surgeons of Edinburgh, and confirmed the presence of silico-tuberculosis in it. The evidence shows that a major epidemic did occur, caused by a combination of factors. The size of the undertaking attracted many stonemasons to Edinburgh over a period of almost 100 years, intensively cutting and dressing stone. The principal stone worked was a very high-quartz sandstone, derived from the local Craigleith quarry, having properties that made it desirable for prestige buildings. However, even before the construction of the New Town, Craigleith sandstone was notorious for its dustiness and the Edinburgh stonemasons worked the stone in unventilated sheds. Stonemasons appeared to be aware of the risk of their trade, but little was known about preventive measures. It appears it was assumed that the risks to stonemasons disappeared after the Craigleith quarry closed, the employers emphasising (without evidence) the lack of health risks in other quarries, and the tragic episode appears to have been forgotten. However, we point to the continuing occurrence of silicosis among stonemasons to the present day; the importance of remembering such episodes is stressed lest the lessons of the past be forgotten.

James Craufurd Gregory, 19th century Scottish physicians, and the link between occupation as a coal miner and lung disease.

By the mid-19th century about 200,000 miners were employed in a UK coal mining industry still growing with the advances of the Industrial Revolution. Coal miners were long known to suffer poor health but the link to inhaling dust in the mines had not been made. In 1813 George Pearson was the first to suggest that darkening of lungs seen in normal individuals as they aged was caused by inhaled soot from burning oil, candles and coal, which were the common domestic sources of heat and light. In 1831 Dr James Craufurd Gregory first described black pigmentation and disease in the lungs of a deceased coal miner and linked this to pulmonary accumulation of coal mine dust. Gregory hypothesised that the black material seen at autopsy in the collier's lungs was inhaled coal dust and this was confirmed by chemical analysis carried out by Professor Sir Robert Christison. Gregory suggested that coal dust was the cause of the disease and warned physicians in mining areas to be vigilant for the disease. This first description of what came to be known as 'coal worker's pneumoconiosis' sparked a remarkable intellectual effort by physicians in Scotland, culminating in a large body of published work that led to the first understandings of this disease and its link to coalblackened lungs. This paper sets out the history of the role of Scottish physicians in gaining this understanding of coal worker's pneumoconiosis. It describes Gregory's case and the lung - recently discovered in the pathology collection of the Surgeons' Hall Museums, Edinburgh, where it has lain unnoticed for over 180 years - on which Gregory based his landmark paper.

Isolated mediastinal lymphadenopathy - performance of EBUS-TBNA in clinical practice.

Background Isolated mediastinal lymphadenopathy is an increasingly common finding as a result of the increasing use of cross-sectional thoracic imaging. We investigated the performance of endobronchial ultrasoundguided transbronchial needle-aspiration (EBUS-TBNA) in establishing a pathological diagnosis in patients with isolated mediastinal lymphadenopathy. Methods We retrospectively analysed all consecutive EBUS-TBNA examinations performed over a 4-year period at a single tertiary referral centre. Final diagnoses were made using pathology reports, correlated with clinical features and the results of any other investigations. Results In total, 126 EBUS-TBNA examinations were performed to investigate isolated mediastinal lymphadenopathy. A positive pathological diagnosis was made following EBUSTBNA in 54 cases (43%). When the results of further investigations and variable radiological follow up were included, the final sensitivity of EBUS-TBNA for making a diagnosis in isolated mediastinal lymphadenopathy was 80% (95% CI 69%-89%). Conclusions This study confirms that EBUS-TBNA has acceptable sensitivity for detecting both benign and malignant pathologies underlying isolated mediastinal lymphadenopathy.

Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial.

BACKGROUND: Elderly people who have a fracture are at high risk of another. Vitamin D and calcium supplements are often recommended for fracture prevention. We aimed to assess whether vitamin D3 and calcium, either alone or in combination, were effective in prevention of secondary fractures. METHODS: In a factorial-design trial, 5292 people aged 70 years or older (4481 [85%] of whom were women) who were mobile before developing a low-trauma fracture were randomly assigned 800 IU daily oral vitamin D3, 1000 mg calcium, oral vitamin D3 (800 IU per day) combined with calcium (1000 mg per day), or placebo. Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months. Analysis was by intention-to-treat and the primary outcome was new low-energy fractures. FINDINGS: 698 (13%) of 5292 participants had a new low-trauma fracture, 183 (26%) of which were of the hip. The incidence of new, low-trauma fractures did not differ significantly between participants allocated calcium and those who were not (331 [12.6%] of 2617 vs 367 [13.7%] of 2675; hazard ratio (HR) 0.94 [95% CI 0.81-1.09]); between participants allocated vitamin D3 and those who were not (353 [13.3%] of 2649 vs 345 [13.1%] of 2643; 1.02 [0.88-1.19]); or between those allocated combination treatment and those assigned placebo (165 [12.6%] of 1306 vs 179 [13.4%] of 1332; HR for interaction term 1.01 [0.75-1.36]). The groups did not differ in the incidence of all-new fractures, fractures confirmed by radiography, hip fractures, death, number of falls, or quality of life. By 24 months, 2886 (54.5%) of 5292 were still taking tablets, 451 (8.5%) had died, 58 (1.1%) had withdrawn, and 1897 (35.8%) had stopped taking tablets but were still providing data for at least the main outcomes. Compliance with tablets containing calcium was significantly lower (difference: 9.4% [95% CI 6.6-12.2]), partly because of gastrointestinal symptoms. However, potentially serious adverse events were rare and did not differ between groups. INTERPRETATION: The findings do not support routine oral supplementation with calcium and vitamin D3, either alone or in combination, for the prevention of further fractures in previously mobile elderly people.

A new classification of glenoid bone loss to help plan the implantation of a glenoid component before revision arthroplasty of the shoulder.

AIMS: Glenoid bone loss can be a challenging problem when revising a shoulder arthroplasty. Precise pre-operative planning based on plain radiographs or CT scans is essential. We have investigated a new radiological classification system to describe the degree of medialisation of the bony glenoid and that will indicate the amount of bone potentially available for supporting a glenoid component. It depends on the relationship between the most medial part of the articular surface of the glenoid with the base of the coracoid process and the spinoglenoid notch: it classifies the degree of bone loss into three types. It also attempts to predict the type of glenoid reconstruction that may be possible (impaction bone grafting, structural grafting or simple non-augmented arthroplasty) and gives guidance about whether a pre-operative CT scan is indicated. PATIENTS AND METHODS: Inter-method reliability between plain radiographs and CT scans was assessed retrospectively by three independent observers using data from 39 randomly selected patients. Inter-observer reliability and test-retest reliability was tested on the same cohort using Cohen's kappa statistics. Correlation of the type of glenoid with the Constant score and its pain component was analysed using the Kruskal-Wallis method on data from 128 patients. Anatomical studies of the scapula were reviewed to explain the findings. RESULTS: Excellent inter-method reliability, inter-observer and test-retest reliability were seen. The system did not correlate with the Constant score, but correlated well with its pain component. TAKE HOME MESSAGE: Our system of classification is a helpful guide to the degree of glenoid bone loss when embarking on revision shoulder arthroplasty.

Early care of acute myocardial infarction.

A fixed life support station (LSS) was established in the emergency department of a community hospital in order to provide early care for patients with suspected acute myocardial infarction (MI). Prospective studies were conducted on 154 patients with verified acute MI. Median time from onset of symptoms to electrocardiographic monitoring was 164 minutes. Overall hospital mortality for these patients was 15.6%. Of 112 patients less than 70 years old, 51 arrived within two hours; only three (6%) of the 51 died. Patients arriving within two hours of the onset of symptoms in clinical class I had an incidence of cardiogenic shock (CS) of 2%, while those arriving two hours or more after the onset of symptoms in clinical class II had an incidence of CS of 26% (P less than .005). A fixed LSS in a community hospital is feasible and effective for early care of patients with acute MI and may facilitate identification of patients at highest risk for development of CS.

Endocarditis with myocardial abscesses and pericarditis in an adult: group B Streptococcus as a cause.

Group B beta-hemolytic Streptococcus, S agalactiae, is an uncommon cause of endocarditis in adults. We present the clinical, laboratory, and postmortem findings of an adult patient with group B streptococcal endocarditis and major arterial emboli. What to our knowledge are previously unreported features are purulent pericarditis and myocardial abscesses. Twenty-five cases of endocarditis caused by group B Streptococcus that are reported in the literature are reviewed.

The biological response to a failed extra-articular polyester ligament used for AC Joint reconstruction at the shoulder girdle: a retrieval analysis of five cases.

The LockDown device (previously called Surgilig) is a braided polyester mesh which is mostly used to reconstruct the dislocated acromioclavicular joint. More than 11,000 have been implanted worldwide. Little is known about the tissue reaction to the device nor to its wear products when implanted in an extra-articular site in humans. This is of importance as an adverse immunological reaction could result in osteolysis or damage to the local tissues, thereby affecting the longevity of the implant. We analysed the histology of five LockDown implants retrieved from five patients over the last seven years by one of the senior authors. Routine analysis was carried out in all five cases and immunohistochemistry in one. The LockDown device acts as a scaffold for connective tissue which forms an investing fibrous pseudoligament. The immunological response at the histological level seems favourable with a limited histiocytic and giant cell response to micron-sized wear particles. The connective tissue envelope around the implant is less organised than a native ligament.

Acromioclavicular joint reconstruction using the LockDown synthetic implant: a study with cadavers.

Dislocation of the acromioclavicular joint is a relatively common injury and a number of surgical interventions have been described for its treatment. Recently, a synthetic ligament device has become available and been successfully used, however, like other non-native solutions, a compromise must be reached when choosing non-anatomical locations for their placement. This cadaveric study aimed to assess the effect of different clavicular anchorage points for the Lockdown device on the reduction of acromioclavicular joint dislocations, and suggest an optimal location. We also assessed whether further stability is provided using a coracoacromial ligament transfer (a modified Neviaser technique). The acromioclavicular joint was exposed on seven fresh-frozen cadaveric shoulders. The joint was reconstructed using the Lockdown implant using four different clavicular anchorage points and reduction was measured. The coracoacromial ligament was then transferred to the lateral end of the clavicle, and the joint re-assessed. If the Lockdown ligament was secured at the level of the conoid tubercle, the acromioclavicular joint could be reduced anatomically in all cases. If placed medial or 2 cm lateral, the joint was irreducible. If the Lockdown was placed 1 cm lateral to the conoid tubercle, the joint could be reduced with difficulty in four cases. Correct placement of the Lockdown device is crucial to allow anatomical joint reduction. Even when the Lockdown was placed over the conoid tubercle, anterior clavicle displacement remained but this could be controlled using a coracoacromial ligament transfer.

Orthostatic hypotension: a commonly unrecognized cause of symptoms in mitral valve prolapse.

To test the hypothesis that orthostatic hypotension could represent an alternative mechanism contributing to the symptoms of mitral valve prolapse, the systolic and diastolic arterial blood pressures were measured in the supine and standing positions in 86 patients with the diagnosis confirmed by echocardiography. Orthostatic hypotension was demonstrated in 12 patients. Ten of them presented with a history of recurrent lightheadedness, dizziness or syncope and constitute 59 percent of the total number of patients with such symptoms in this series. Although nine of these 10 patients reported transient lightheadedness or dizziness during periods of ambulatory electrocardiographic recording, in only one were the symptoms chronologically related to cardiac arrhythmias. On the other hand, eight of them described lightheadedness and two experienced near-syncope during the postural test in association with the orthostatic drop in blood pressure. Improvement in symptoms and correction of the orthostatic hypotension were demonstrated in seven patients after beta-adrenergic blockade with propranolol. Before therapy, the mean systolic blood pressure dropped from 114 +/- 3 mm Hg in the supine position to 78 +/- 1 mm Hg upon standing (p less than 0.001). In repeated postural tests performed after four weeks of treatment, the systolic blood pressure changed from 120 +/- 3 mm Hg supine to 115 +/- 1 mm Hg upon standing (p greater than 0.01). We conclude that orthostatic hypotension is a commonly unrecognized mechanism responsible for some of the symptoms of mitral valve prolapse, particularly in patients affected by recurrent lightheadedness, dizziness or syncope.