Lawsonella clevelandensis causing spinal subdural empyema.

Lawsonella clevelandensis is a recently described species and genus of bacterium in the Corynebacterineae suborder which is Gram-stain positive, partially acid-fast and anaerobic. Very few cases of human infection due to this organism are described and here we seek to add to the limited medical literature. We report the case of a 2-year-old girl who presented with an infected spinal dermoid cyst secondary to Lawsonella clevelandensis which required surgical drainage and a long course of antibiotics. We encountered diagnostic and therapeutic difficulties because this is a fastidious organism which was difficult to culture and ultimately required molecular detection and identification. To the best of our knowledge, this is only the seventh reported case of Lawsonella clevelandensis causing human infection worldwide and the first in the UK. This is the first reported case of Lawsonella clevelandensis infection in a child and the second reported case of this organism causing spinal infection.

Does dermatoneuro syndrome have a viral aetiology?

Scleromyxoedema is a rare disease characterized by a generalized papular and sclerodermoid cutaneous eruption. It is associated with fibroblast proliferation and mucin deposition in the dermis. Most patients have a monoclonal gammopathy, defined by the presence of IgG. Treatment of scleromyxoedema is challenging, but there is mounting evidence to support the use of intravenous immunoglobulin (IVIg). Individual reports of systemic complications have been described. Dermatoneuro syndrome (DNS) is a rare but sometimes fatal manifestation, which consists of a triad of fever, coma and seizures preceded by a flu-like illness. We describe a patient with scleromyxoedema who developed DNS. Our case highlights interesting findings suggesting that DNS may have a viral aetiology. In addition, this case demonstrates a favourable response of the cutaneous features of scleromyxoedema to IVIg.

Novel high-efficiency 2D position-sensitive ZnS:Ag/6LiF scintillator detector for neutron diffraction.

Scintillator-based ZnS:Ag/6LiF neutron detectors have been under development at ISIS for more than three decades. Continuous research and development aim to improve detector capabilities, achieve better performance and meet the increasingly demanding requirements set by neutron instruments. As part of this program, a high-efficiency 2D position-sensitive scintillator detector with wavelength-shifting fibres has been developed for neutron-diffraction applications. The detector consists of a double scintillator-fibre layer to improve detection efficiency. Each layer is made up of two orthogonal fibre planes placed between two ZnS:Ag/6LiF scintillator screens. Thin reflective foils are attached to the front and back scintillators of each layer to minimize light cross-talk between layers. The detector has an active area of 192 × 192 mm with a square pixel size of 3 × 3 mm. As part of the development process of the double-layer detector, a single-layer detector was built, together with a prototype detector in which the two layers of the detector could be read out separately. Efficiency calculations and measurements of all three detectors are discussed. The novel double-layer detector has been installed and tested on the SXD diffractometer at ISIS. The detector performance is compared with the current scintillator detectors employed on SXD by studying reference crystal samples. More than a factor of 3 improvement in efficiency is achieved with the double-layer wavelength-shifting-fibre detector. Software routines for further optimizations in spatial resolution and uniformity of response have been implemented and tested for 2D detectors. The methods and results are discussed in this manuscript.

Association between white matter ischaemia and carotid plaque morphology as defined by high-resolution in vivo MRI.

OBJECTIVES AND DESIGN: Both carotid plaque morphology and severity of white matter ischaemia (WMI) have been shown to be independent predictors of stroke risk. This study tests the hypothesis that there is an association between carotid plaque morphology as determined by high-resolution carotid MRI and WMI. MATERIALS AND METHODS: Forty patients (80 arteries) with at least 40% stenosis on screening Doppler ultrasound were recruited and underwent high-resolution axial carotid MRI at 1.5 T. In a blinded manner, plaque characteristics such as lipid core, fibrous cap, intraplaque haemorrhage, lumen area, plaque area, and American Heart Association (AHA) classification were qualitatively and quantitatively evaluated. The severity of WMI was independently quantified using a modified Scheltens score based on standard brain Fluid-Attenuated Inversion Recovery. Linear mixed effect models were used to test if carotid plaque characteristics could independently predict severity of WMI. RESULTS: Hypertension (p=0.005) and previous a history of transient ischaemic attack or stroke (p=0.038) were found to be significant predictors of severity of WMI. After accounting for confounding variables, no significant association was found between the modified Scheltens score and lipid core size (p=0.122), fibrous cap status (p=0.991), intraplaque haemorrhage (p=0.708), plaque area (0.835), lumen area (0.371) or an AHA Type VI complex plaque (p=0.195). CONCLUSIONS: Carotid plaque morphology as defined by MRI does not independently predict severity of WMI.

Temporal dependence of in vivo USPIO-enhanced MRI signal changes in human carotid atheromatous plaques.

INTRODUCTION: Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced MRI has been shown to be a useful modality to image activated macrophages in vivo, which are principally responsible for plaque inflammation. This study determined the optimum imaging time-window to detect maximal signal change post-USPIO infusion using T1-weighted (T1w), T2*-weighted (T2*w) and quantitative T2* (qT2*) imaging. METHODS: Six patients with an asymptomatic carotid stenosis underwent high resolution T1w, T2*w and qT2* MR imaging of their carotid arteries at 1.5 T. Imaging was performed before and at 24, 36, 48, 72 and 96 h after USPIO (Sinerem, Guerbet, France) infusion. Each slice showing atherosclerotic plaque was manually segmented into quadrants and signal changes in each quadrant were fitted to an exponential power function to model the optimum time for post-infusion imaging. RESULTS: The power function determining the mean time to convergence for all patients was 46, 41 and 39 h for the T1w, T2*w and qT2* sequences, respectively. When modelling each patient individually, 90% of the maximum signal intensity change was observed at 36 h for three, four and six patients on T1w, T2*w and qT2*, respectively. The rates of signal change decrease after this period but signal change was still evident up to 96 h. CONCLUSION: This study showed that a suitable imaging window for T1w, T2*w and qT2* signal changes post-USPIO infusion was between 36 and 48 h. Logistically, this would be convenient in bringing patients back for one post-contrast MRI, but validation is required in a larger cohort of patients.

Characterisation of carotid atheroma in symptomatic and asymptomatic patients using high resolution MRI.

BACKGROUND AND PURPOSE: To prospectively evaluate differences in carotid plaque characteristics in symptomatic and asymptomatic patients using high resolution MRI. METHODS: 20 symptomatic and 20 asymptomatic patients, with at least 50% carotid stenosis as determined by Doppler ultrasound, underwent preoperative in vivo multispectral MRI of the carotid arteries. Studies were analysed both qualitatively and quantitatively in a randomised manner by two experienced readers in consensus, blinded to clinical status, and plaques were classified according to the modified American Heart Association (AHA) criteria. RESULTS: After exclusion of poor quality images, 109 MRI sections in 18 symptomatic and 19 asymptomatic patients were available for analysis. There were no significant differences in mean luminal stenosis severity (72.9% vs 67.6%; p = 0.09) or plaque burden (median plaque areas 50 mm(2) vs 50 mm(2); p = 0.858) between the symptomatic and asymptomatic groups. However, symptomatic lesions had a higher incidence of ruptured fibrous caps (36.5% vs 8.7%; p = 0.004), haemorrhage or thrombus (46.5% vs 14.0%; p<0.001), large necrotic lipid cores (63.8% vs 28.0%; p = 0.002) and complicated type VI AHA lesions (61.5% vs 28.1%; p = 0.001) compared with asymptomatic lesions. The MRI findings of plaque haemorrhage or thrombus had an odds ratio of 5.25 (95% CI 2.08 to 13.24) while thin or ruptured fibrous cap (as opposed to a thick fibrous cap) had an odds ratio of 7.94 (95% CI 2.93 to 21.51) for prediction of symptomatic clinical status. CONCLUSIONS: There are significant differences in plaque characteristics between symptomatic and asymptomatic carotid atheroma and these can be detected in vivo by high resolution MRI.

Combined PET-FDG and USPIO-enhanced MR imaging in patients with symptomatic moderate carotid artery stenosis.

INTRODUCTION: PET-FDG and USPIO-enhanced MRI are increasingly being used in depicting carotid atheroma inflammation--a risk factor for the high risk plaque. Their combined use has not been previously reported. REPORT: Two patients presenting with stroke and identified with 50% carotid stenosis on duplex ultrasonography, underwent PET FDG and USPIO-enhanced MR imaging. Results were concordant and complementary suggesting that both techniques reflect similar metabolic processes. DISCUSSION: The selection of patients for carotid revascularisation has largely been based on the severity of luminal stenosis alone. The two imaging modalities, which identify inflammatory activity, may be potential surrogate risk markers in the selection of patients eligible for carotid surgery, if plaque inflammation can be correlated with risk of developing clinical symptoms.

Comparison of the inflammatory burden of truly asymptomatic carotid atheroma with atherosclerotic plaques in patients with asymptomatic carotid stenosis undergoing coronary artery bypass grafting: an ultrasmall superparamagnetic iron oxide enhanced magnetic resonance study.

INTRODUCTION: Inflammation is a recognized risk factor for the vulnerable atherosclerotic plaque. The aim of this study was to explore whether there is a difference in the degree of Magnetic Resonance (MR) defined inflammation using Ultra Small Super-Paramagnetic Iron Oxide (USPIO) particles, within carotid atheroma in completely asymptomatic individuals and the asymptomatic carotid stenosis in a cohort of patients undergoing coronary artery bypass grafting (CABG). METHODS: 10 patients awaiting CABG with asymptomatic carotid disease and 10 completely asymptomatic individuals with no documented coronary artery disease underwent multi-sequence MR imaging before and 36 hours post USPIO infusion. Images were manually segmented into quadrants and signal change in each quadrant, normalised to adjacent muscle signal, was calculated following USPIO administration. RESULTS: The mean percentage of quadrants showing signal loss was 94% in the CABG group, compared to 24% in the completely asymptomatic individuals (p<0.001). The carotid plaques from the CABG patients showed a significant mean signal intensity decrease of 16.4% after USPIO infusion (95% CI 10.6% to 22.2%; p<0.001). The truly asymptomatic plaques showed a mean signal intensity increase (i.e. enhancement) after USPIO infusion of 8.4% (95% CI 2.6% to 14.2%; p=0.007). The mean signal difference between the two groups was 24.9% (95% CI 16.7% to 33.0%; p<0.001). CONCLUSIONS: These findings are consistent with the hypothesis that inflammatory atheroma is a systemic disease. The carotid territory is more likely to take up USPIO if another vascular territory is symptomatic.

Is the recommended target of 4 hours from head injury to emergency craniotomy achievable?

Guidelines recommend that head-injured patients who require life-saving decompressive surgery should undergo surgery within 4 h. To assess the compliance with this recommendation 100 consecutive head-injured patients admitted to a regional neurosurgical unit (RNU) were studied. Time points from head injury to craniotomy were documented and analysed. Twenty-four patients underwent emergency craniotomy, only one being operated on within 4 h. In this cohort of patients there was no relationship between timing of surgery and outcome. In order to investigate whether it is possible to reduce delays in transportation time, theoretical models were created to determine whether direct transfer to the RNU would be faster by land or air ambulance.

Role of thromboxane A2 in the vasoconstrictor response to endothelin-1, angiotensin II and 5-hydroxytryptamine in human placental vessels.

The possibility that the vasoconstrictor agents present in the circulation may mediate their effect on placental blood flow by stimulating local prostanoid production was investigated. Placental cotyledons obtained at term from normal pregnancies were perfused in vitro. The dose-related vasoconstrictor effects of endothelin-1 (ET-1), angiotensin II (A II) and 5-hydroxytryptamine (5 HT) were reduced by graded concentrations of the thromboxane A2 (TXA2) receptor antagonist GR32191 (10(-7)-10(-4)M), aspirin (10(-5)-10(-4)M) and indomethacin (10(-5)M). The effect of the TXA2 receptor agonist U46619 was totally abolished by GR32191 (10(-7)M) but unaffected by the prostanoid synthesis inhibitors, aspirin and indomethacin although they prevented a self-priming effect of U46619. When effluents were collected from perfused placentae, 5-10 min after administration of sub-maximal doses of ET-1 (20 pmol), A II (500 pmol) and 5 HT (15 pmol), there was a significant increase in TXB2, the stable metabolite of TXA2, indicating the vasoconstrictors had induced an increase in local prostanoid production. These findings indicate that the vasoconstrictor effects of ET-1, A II and 5 HT in the placental vascular bed are mediated, at least in part, by vasoconstrictor prostanoids including TXA2.

Rapid and sensitive detection of anti-Ro (SS-A) antibodies by indirect immunofluorescence of 60kDa Ro HEp-2 transfectants.

Anti-Ro (SS-A) antibodies are important diagnostic markers for primary Sjögren's syndrome and systemic lupus erythematosus, but their detection by indirect immunofluorescence (IF) in the diagnostic laboratory is hindered by the low cellular abundance of 60kDa Ro protein (Ro60). The approach we used to overcome this problem was to transfect and over-express the Ro60 gene into HEp-2 cells. In this study we have used a mixture of Ro60 transfectants and untransfected HEp-2 cells (HEp-Ro60) as a substrate for IF-antinuclear antibody (ANA) testing in a hospital laboratory. Screening of 240 routine serum specimens identified 14 Ro transfectant-positive sera which were confirmed by counterimmunoelectrophoresis (CIE); 3 of these sera were ANA-negative on untransfected cells and regular HEp-2. A comparison of HEp-Ro60 and regular HEp-2 showed strong concordance of the different ANA patterns between the 2 substrates. No increase in background staining was observed on the Ro transfectants when reacted with normal human sera. A comparison between HEp-Ro60 and CIE for 53 sera from patients with primary Sjögren's syndrome showed that HEp-Ro60 were a sensitive and specific substrate for detection of anti-Ro antibodies. Masking of positive Ro transfectants was observed rarely in sera containing multiple ANA specificities, but the Ro60 staining on these transfectants were unmasked at higher serum dilutions. We conclude that HEp-Ro60 are a suitable substrate for IF-ANA in the routine laboratory and that they have the additional advantage over regular HEp-2 slides of being able to detect anti-Ro in ANA-negative sera. HEp-RO60 are also a valuable confirmatory test for sera giving equivocal precipitin reactions or ELISA results.

On the implications of interpreting the stability index: a spine example.

Quantifying the stability of the spinal column offers a perspective on the effectiveness of the motor control strategy to ensure a stable spine--and minimize the risk of injury from experiencing an unstable event. There are essentially three energy based methods of calculating a stability index for the lumbar spine. All three methods involve mathematical manipulation of an 18 x 18 Hessian matrix. The purpose of this paper was to consider the mathematical implications for the three methods of determining a single stability index, and examine the effects of biological factors such as muscle activation in each of these methods. The first approach computes the Hessian's determinant and is thought to represent a more global or "average" perspective on stability. A second approach computes the smallest eigenvalue of the Hessian matrix to determine the weakest link of the spine. The final method determines an average critical stiffness difference for the spine and is intended to effectively determines how far a human spine is from instability, and allows comparison between tasks. This study shows that the same interpretation of stability is achieved via all three computational approaches--they agree as to whether the spine is stable or not. However they appear to differ in their sensitivity to the effect of muscle activation patterns.

The water quality of the River Kennet: initial observations on a lowland chalk stream impacted by sewage inputs and phosphorus remediation.

The water quality of seven sites on the upper reaches of the River Kennet round the market town of Marlborough is described and related to the introduction of phosphorus treatment of effluent from Marlborough sewage treatment works (STW). The River Kennet is mainly groundwater-fed from a Cretaceous chalk aquifer and hence the river water is calcium- and bicarbonate-bearing and has a relatively constant composition of many major water quality determinants. In-stream biological activity gives rise to marked diurnal fluctuations in pH (of approx. 0.8 units). Dissolved carbon dioxide and dissolved oxygen also show marked diurnal fluctuations. Dissolved carbon dioxide varies from approximately 10 to 70 times atmospheric pressure, indicating net release of carbon dioxide and the dominance of heterotrophic (respiratory) processes over autotrophic processes (photosynthesis). Much of the excess carbon dioxide is probably associated with carbon dioxide laden groundwater inputs and the relatively short within-stream residence times ensures only limited degassing to the atmosphere. Diurnal fluctuations in dissolved oxygen vary from approximately 20% to 200% saturation. For both dissolved carbon dioxide and dissolved oxygen, the amplitude of fluctuations is much lower during the winter period, when biological activity is at its lowest. The concentrations of soluble reactive phosphorus (SRP), total phosphorus (TP) and boron increase markedly just downstream of the sewage works as a result of this point source input. These concentrations slowly decline further downstream as additional groundwater inputs dilute the effluent further. The introduction of chemical treatment of sewage effluent for phosphorus reduction at Marlborough STW resulted in a marked decrease in within-river SRP and TP concentrations to levels approximately the same as those upstream of the STW. A comparison of SRP and boron concentrations reveals a reduction in in-stream SRP concentrations by approximately 75% following effluent treatment. In terms of within-river processes controlling in-stream phosphorus concentrations, previous studies have indicated that one potentially important mechanism within calcium bicarbonate bearing rivers may be related to co-precipitation of phosphorus with calcium carbonate (calcite). The present study shows that the waters are oversaturated with respect to calcium carbonate, that no equilibrium conditions exist and that phosphorus removal has led to undetectable changes in calcium carbonate oversaturation. Hence, it is concluded that the primary changes in phosphorus levels within the river is directly associated with changing point source contributions from the STW and physical dilution within the river. However (1) the results relate to only the first year of study and subsequent differences may become apparent and (2) reactions between the water column and plant and bottom sediment interfaces may be important in regulating phosphorus fluxes within the river. The results presented in this paper mark a pilot phase of a longer-term initiative and this paper provides a background setting. The paper discusses the longer-term objectives and important gaps in knowledge of the system that requires further address.

Squamous cell carcinoma of the equine external genitalia: a review and assessment of penile amputation and urethrostomy as a surgical treatment.

A retrospective analysis was performed on 48 cases of suspected neoplasia involving the equine external genitalia. Forty nine squamous cell carcinomata (SCC) and 23 squamous papillomata (SP) were identified. Two cases of epithelial hyperplasia and one case of habronemiasis were also recognised histopathologically. The glans penis was the most common site of tumour development accounting for 53 per cent of cases of SCC and 61 per cent of SP. The urethral diverticulum, urethral process or urethra was involved in 27.6 per cent (8/29) of cases of SCC. Twelve per cent (5/41) of cases of SCC were confirmed to have metastatic involvement of the local lymph nodes. Papillomata showing pre-malignant changes were identified in five cases. Seventy five per cent (36/48) of the animals presented were ponies. All were geldings, mean age 16.5 years. Penile amputation and urethrostomy, preputial ablation and proximal urethrostomy or local excision were used in the surgical management of these animals; three cases were inoperable and destroyed at presentation. Oedema, haemorrhage and stenosis of the urethrostomy site were encountered as post operative complications. Sixty six per cent (6/9) of animals with SCC of the glans penis (without urethral involvement), which had a known history over the follow up period, treated by penile amputation and urethrostomy survived for longer than 18 months. Similarly, of those with urethral involvement only 28.6 per cent (2/7) survived for a similar follow-up period. SCC not uncommonly affects the external genitalia of aged pony geldings and frequently the glans penis. If the lesion is identified before local metastasis occurs, penile amputation and urethrostomy is indicated and the prognosis is favourable.

Activated partial thromboplastin time reagents: an evaluation.

Nine automated, activated partial thromboplastin time (APTT) reagents were evaluated on an automated coagulometer, in comparison with a manual reagent. The study consisted of three separate stages: 1) to choose a reagent that had a working stability between 4 degrees C and 8 degrees C for seven days and heparin sensitivity between 0 and 0.8 iu/ml; ii) assessment of sensitivity to specific factor deficiencies, particularly factors VIII, IX, XI and XII using standardised plasma serially diluted with factor-deficient plasma; and iii) assessment of sensitivity to the presence of a lupus anticoagulant, from a known positive panel. Only one reagent fulfilled all the essential criteria as an acceptable replacement for the manual reagent.

Platelet indices during normal pregnancy and pre-eclampsia.

Platelet count and mean platelet volume (MPV) were estimated in 349 normal pregnancies at various gestational stages, and in 30 cases of pre-eclampsia. A probability plot was constructed from these data using discriminant analysis of MPV versus platelet count for the pre-eclamptic versus normal pregnancies. The sensitivity for pre-eclampsia was 90% (27/30) and the specificity was 83.3%. This plot may be of use in confirming risk of pre-eclampsia.

Mortality in elderly patients admitted for respite care.

OBJECTIVE: To determine whether admitting elderly patients to hospital to give temporary relief to their carers is associated with increased mortality. DESIGN: Prospective multicentre study comparing the mortality of patients admitted on a one off or rotational basis with that experienced while they were awaiting admission. SETTING: A wide range of urban and rural district general, geriatric or long stay, and general practitioner hospitals. PATIENTS: 474 Patients aged 70 or over who had 601 admissions. MAIN OUTCOME MEASURE: Death. RESULTS: 16 (3.4%) Of the 474 patients (2.7% of all 601 admissions) died while in hospital during an average stay of 15.7 days whereas 23 (4.9%) patients died while awaiting admission (average waiting time was 34.2 days). The 16 deaths in hospital and the 23 deaths during the longer waiting period correspond to death rates of 19.9 and 12.5 per 10,000 person days respectively. The difference between these of 7.4 is not statistically significant (95% confidence interval -3.6 to 18.3). The estimated relative risk of dying in hospital is 1.59 but the 95% confidence interval is wide (0.84 to 3.01). CONCLUSION: Although the death rates are slightly higher in those admitted to hospital for relief care than in those awaiting admission, the difference was not significant, and the death rate in both groups was reassuringly small.