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Background Allopurinol has vascular antioxidant effects and participates in purinergic signalling within muscle. We tested whether allopurinol could improve skeletal muscle energetics and physical function in older people with impaired physical performance. Methods We conducted a randomised, double blind, parallel group, placebo-controlled trial, comparing 20 weeks of allopurinol 600 mg once daily versus placebo. We recruited community-dwelling participants aged 65 and over with baseline 6-min walk distance of Results In total, 124 participants were randomised, mean age 80 (SD 6) years. A total of 59 (48%) were female, baseline 6-min walk distance was 293 m (SD 80 m) and baseline SPPB was 8.5 (SD 2.0). Allopurinol did not significantly improve PCr recovery rate (treatment effect 0.10 units [95% CI, −0.07 to 0.27], P = 0.25). No significant changes were seen in endothelial function, quality of life, lean body mass or SPPB. Allopurinol improved 6-min walk distance (treatment effect 25 m [95% 4–46, P = 0.02]). This was more pronounced in those with high baseline oxidative stress and urate. Conclusion Allopurinol improved 6-min walk distance but not PCr recovery rate in older people with impaired physical function. Antioxidant strategies to improve muscle function for older people may need to be targeted at subgroups with high baseline oxidative stress.

Purpose To quantify the burden and distribution of asymptomatic atherosclerosis in a population with a low to intermediate risk of cardiovascular disease. Materials and Methods Between June 2008 and February 2013, 1528 participants with 10-year risk of cardiovascular disease less than 20% were prospectively enrolled. They underwent whole-body magnetic resonance (MR) angiography at 3.0 T by using a two-injection, four-station acquisition technique. Thirty-one arterial segments were scored according to maximum stenosis. Scores were summed and normalized for the number of assessable arterial segments to provide a standardized atheroma score (SAS). Multiple linear regression was performed to assess effects of risk factors on atheroma burden. Results A total of 1513 participants (577 [37.9%] men; median age, 53.5 years; range, 40-83 years) completed the study protocol. Among 46 903 potentially analyzable segments, 46 601 (99.4%) were interpretable. Among these, 2468 segments (5%) demonstrated stenoses, of which 1649 (3.5%) showed stenosis less than 50% and 484 (1.0%) showed stenosis greater than or equal to 50%. Vascular stenoses were distributed throughout the body with no localized distribution. Seven hundred forty-seven (49.4%) participants had at least one stenotic vessel, and 408 (27.0%) participants had multiple stenotic vessels. At multivariable linear regression, SAS correlated with age (B = 3.4; 95% confidence interval: 2.61, 4.20), heart rate (B = 1.23; 95% confidence interval: 0.51, 1.95), systolic blood pressure (B = 0.02; 95% confidence interval: 0.01, 0.03), smoking status (B = 0.79; 95% confidence interval: 0.44, 1.15), and socioeconomic status (B = -0.06; 95% confidence interval: -0.10, -0.02) (P < .01 for all). Conclusion Whole-body MR angiography identifies early vascular disease at a population level. Although disease prevalence is low on a per-vessel level, vascular disease is common on a per-participant level, even in this low- to intermediate-risk cohort. © RSNA, 2018 Online supplemental material is available for this article.

Short-axis cine images are acquired during cardiac MRI in order to determine variables of cardiac left ventricular (LV) function such as ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and LV mass. In cardiac perfusion assessments this imaging can be performed in the temporal window between first pass perfusion and the acquisition of delayed enhancement images in order to minimise overall scanning time. The objective of this study was to compare pre- and post-contrast short-axis LV variables of 15 healthy volunteers using a two-dimensional cardiac-gated segmented cine true fast imaging with steady state precession sequence and a 3.0 T MRI unit in order to determine the possible effects of contrast agent on the calculated cardiac function variables. Image analysis was carried out using semi-automated software. The calculated mean LV mass was lower when derived from the post-contrast images, relative to those derived pre-contrast (102 vs 108.1 g, p

Recent improvements in MR image acquisition and post-processing techniques have allowed quantitative kidney volume measurements to be derived from patient studies. These morphological indices can provide "snapshot" assessments that may be related to kidney function. The study objective was to measure cortical and total kidney volumes in patients with renovascular disease (RVD) using contrast-enhanced MR angiography (CE-MRA) in order to assess the reproducibility of the technique and to investigate associations between volumes and renal function as measured by glomerular filtration rate (GFR) calculations. 50 patients with RVD were scanned using CE-MRA. Kidney lengths, volumes and renal artery stenoses (RAS) were evaluated, and GFR was calculated using clinical formulae and nuclear medicine isotope renography. Mean MRI kidney lengths were 10.3+/-0.2 cm, and mean MRI volumes were 74.9+/-3.6 cm3 (cortical) and 128.5+/-5.3 cm3 (total). Kidneys supplied by moderately stenosed arteries had enlarged lengths and volumes, whilst those supplied by severely stenosed arteries had significantly smaller lengths (p

The results of the management of 115 patients with intradural spinal tumours are presented. Data was collected retrospectively from the case notes. Tumours were categorized as intramedullary or extramedullary for statistical analysis. Meningioma, schwannoma and ependymoma accounted for 70% of tumours. Complete macroscopic excision was achieved in 84% of extramedullary and 54% of intramedullary tumours. There were two post-operative deaths, one of which was secondary to methacillin-resistant staphylococcus aureus (MRSA) meningitis. Cerebrospinal fluid leak (10%) and meningitis (7%) were the commonest complications. Ninety-six percent of patients with extramedullary tumours improved or remained unchanged on the Frankel scale. In the intramedullary group, 82% remained unchanged or improved after treatment. Pre-operative functional status was a predictor of good post-operative function for intra- and extramedullary tumours and for intramedullary tumours a good post-operative Frankel score predicted long-term survival.

We demonstrate a role for nonactivated rat microglia in the survival and maturation of oligodendrocyte precursor cells (OPCs). Media conditioned by nonactivated microglia increase the number of surviving galactocerebroside(+) (GalC(+)) oligodendrocytes in vitro at 48 h by inhibiting the apoptosis of OPCs and stimulating their maturation to GalC+ oligodendrocytes. These effects are not observed with medium conditioned by microglia activated with interferon-gamma (IFN-gamma). Conditioned medium from nonactivated microglia is associated with upregulation in OPCs of nuclear factor of kappa binding (NF-kappa B) p65 subunit. The use of antisense to the inhibitor of kappa binding (I kappa B) induces p65 subunit activation in OPCs and, in common with medium conditioned by nonactivated microglia, also inhibits OPC apoptosis and promotes cell maturation. Anti-platelet-derived growth factor (PDGF) antibody abolishes this effect even though PDGF-A chain is expressed at similar levels within both nonactivated and IFN-gamma-activated microglia and both conditioned media have similar levels of PDGF-A chain bioactivity. However, only conditioned medium from nonactivated microglia recruit phosphatidyl-3-inositol (PI-3) kinase to the PDGF-alpha receptor and synergise with endogenous PDGF-A chain to increase NF-kappa B activation. These results suggest that, dependent on their state of activation, microglia produce soluble factors that promote oligodendrocyte development through an effect on the PDGF-alpha receptor-signalling pathway.

Activated microglia are implicated in the injury of neurones and macroglia both in vitro and in vivo. Here, we demonstrate that media conditioned by interferon-gamma treated microglia initially impair the metabolism of mouse cerebellar neurones grown in serum-free conditions without inducing cell death. Metabolic effects include inhibition of the ability of mitochondria to reduce 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and cytochrome oxidase activity. These effects are blocked by antibodies to tumour necrosis factor-alpha (TNFalpha), a cytokine produced by microglial activation, and they are not reproduced by media conditioned by resting microglia. The metabolic effects are evident for up to 24 h in vitro. More prolonged exposure, up to 48 h, results in TNFalpha dependent neuronal death as previously observed. Between 2 and 48 h TNFalpha present in media conditioned by interferon-gamma treated but not resting microglia is associated with nuclear factor kappa B (NF-kappaB) consensus sequence binding in paired mouse cerebellar neuronal cultures without affecting activation of the signal transducer and activator of transcription (STAT) transcription factor. Neuronal death can be accelerated by peptide blockade of the nuclear transport of NF-kappaB p52 subunit during exposure of cerebellar neurones to medium from interferon-gamma treated microglia. This toxicity is blocked by anti-TNFalpha antibody. Soluble factors released by activated microglia therefore contribute to neuronal dysfunction that is initially reversible but may culminate in neurotoxicity. Characterizing and manipulating these events in vivo theoretically provides an opportunity for neuroprotection in selected diseases affecting the central nervous system.

A clinical audit was carried out to determine the impact of multidisciplinary rehabilitation in a specialist neurorehabilitation unit, and to demonstrate how outcome measurement can be incorporated into routine clinical audit. The study describes and interprets the results of one year's activity and outcome in a neurorehabilitation unit. A total of 138 patients were admitted to the 18 bedded unit between April 1994 and March 1995. The main outcome measures were: length of inpatient stay, admission and discharge destination, disability as measured by the Barthel Index and Functional Independence Measure, handicap as measured by the Environmental Status Scale and the Handicap Assessment Scale, and the time spent undertaking the audit. Improvement in disability was demonstrated in 112 (83%) patients and in handicap in 89 (66%) patients. The time taken to analyse the data on a quarterly basis was reduced from 20 hours for the first quarter to 4.5 hours for the last quarter. The results show that multidisciplinary inpatient neurorehabilitation leads to functional improvement in the majority of neurologically impaired patients. Outcome measurement and data collection can be incorporated into routine clinical practice once a sound methodology has been established.