Early neurological deterioration in acute stroke.
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Biomedical subjects
Publications and source records attributed to M Barber.
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BACKGROUND: It has been hypothesised that elevated serum troponin levels in acute stroke are due to myocardial damage caused by sympathoadrenal activation, which, in turn, may be due particularly to insular damage. We aimed to determine the factors associated with troponin elevation in ischaemic stroke and the prognostic value of this finding. METHODS: We studied 222 consecutive acute ischaemic stroke admissions. Serum troponin I and catecholamines were measured. Ischaemic damage on brain computed tomography (CT) scan was graded using the Alberta Stroke Program Early CT Score (ASPECTS). Electrocardiograms were classified using the Minnesota Code and the European Society of Cardiology/American College of Cardiology criteria for acute myocardial infarction. The Rankin scale was recorded at 30 days. RESULTS: Forty-five patients (20%) had troponin I >0.2 microg/l. These troponin-positive patients had higher epinephrine levels (median 0.27 vs. 0.17 nmol/l; p = 0.0002) and were more likely to have electrocardiograms coded as definite or possible acute myocardial infarction (odds ratio 3.35; 95% CI 1.26-8.93), compared with those with troponin < or = 0.2 microg/l, in univariate analysis. There were no significant associations between troponin I score and ASPECTS or insular damage on brain CT. In logistic regression analyses, elevated troponin was significantly associated with age, elevated serum creatinine and epinephrine; however, increased troponin was not an independent predictor of death or dependency (Rankin >2) at 30 days. CONCLUSIONS: Raised troponin I is associated with elevation of circulating epinephrine in acute ischaemic stroke. Activation of the sympathoadrenal system may be an important contributor to myocardial damage in these patients. Increased troponin is not associated with insular damage and does not independently predict poor outcome.
BACKGROUND: Atrial fibrillation (AF) is associated with cognitive impairment and dementia, perhaps through encouraging a prothrombotic state and cardioembolism. OBJECTIVES: We wished to test the hypotheses that hemostatic function is altered in subjects with AF who develop dementia, and that long-term warfarin anticoagulation is protective against this complication. PATIENTS AND METHODS: Recruitment was from an observational cohort study of AF. Baseline assessment included measurement of plasma fibrinogen, fibrin D-dimer, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complexes (TAT), von Willebrand factor and tissue plasminogen activator. We assessed cognitive function after 3 years' follow-up using the 13-item modified Telephone Interview for Cognitive Status (TICSm) and the short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). RESULTS: Of the 218 subjects assessed, 145 (66%) were prescribed warfarin. Forty-nine (22%) met TICSm/IQCODE criteria for dementia. D-dimer, F1+2 and TAT levels were higher in AF subjects with dementia compared with those without (medians 81 vs. 60 ng mL(-1), P = 0.008; 0.76 vs. 0.49 nmol L(-1), P = 0.006; and 1.78 vs. 1.44 microg L(-1), P = 0.003, respectively). These associations became of borderline statistical significance following adjustment for age. Logistic regression showed a trend towards warfarin use being independently associated with reduced prevalence of dementia (odds ratio 0.52, P = 0.08). CONCLUSIONS: We found evidence of increased thrombin generation and fibrin turnover in subjects with AF and dementia compared with those without dementia. Long-term warfarin use may be protective against the development of dementia in subjects with AF.
BACKGROUND: Primary intracerebral haemorrhage (PICH) is associated with a poorer outcome than cerebral infarction. This study aimed to determine whether this is explained by the clinical severity of stroke. METHODS: An observational study of outcome in consecutive admissions with acute PICH and ischaemic stroke was undertaken. A nested case-control analysis, matched on a 1:2 basis for age, pre-stroke disability, early neurological impairment (Scandinavian Stroke Scale; SSS), and Oxfordshire Community Stroke Project classification was then performed. Follow up was at 30 days and at hospital discharge. RESULTS: Overall, 679 subjects were included in the analysis. Of these, 53 (8%) had PICH; this group had more severe initial neurological impairment (day 3 SSS 28 v 45 points, p<0.001) and a higher prevalence of total anterior circulation strokes (55% v 21%, p<0.001) than did the group admitted with ischaemic strokes. Outcomes were poorer in the PICH group, with 36% inpatient mortality and 68% of survivors having a day 30 modified Rankin Scale (MRS) of at least 3 (compared with 13% and 52%, respectively, in the ischaemic stroke group). Following matching for baseline clinical characteristics, the PICH group had a higher mortality, but this was not statistically significant; the day 30 MRS and institutionalisation rates in survivors were similar in the matched haemorrhage and infarct groups. CONCLUSIONS: Compared with ischaemic stroke, PICH is associated with higher mortality and increased disability in survivors. The severity of clinical stroke is a major contributor to these poor outcomes; baseline characteristics, however, do not fully explain outcome differences.
All mainstream primary schools in Cardiff were invited in July 1998 to participate in a prevalence survey of autistic spectrum disorder. Teachers of each class filled in a questionnaire based on ICD-10 criteria for autistic disorders. The Autism Spectrum Screening Questionnaire (ASSQ) was completed on children identified with problems identified by the questionnaire. A total of 11692 children born between 1 September 1986 and 31 August 1990 were screened: 234 (2%) children were identified as requiring an ASSQ; 151 of 234 (65%) ASSQs were returned. Of the 151, 60 children (52 male, 8 female; 40%) scored 22 or more. Their notes and the involved professionals were consulted. Thirty-five children, unknown to specialist services or with complex features, required additional assessment. Seventeen children (all male) were found to be on the autistic spectrum. When the overall rubric was disentangled we found a diverse population of affected children including a handful who did not fit easily into ICD-10 classification. Correcting for incomplete ascertainment we found a minimum prevalence of 20.2 out of every 10 000 (SE = 4.5) for autistic spectrum disorder in this population.
We compared the tandem mass spectra of a range of native and acetylated Ag(+) cationized peptides to determine the influence of the derivatization step on the abundance of the [b(n) + 17 + Ag](+) product ions. Using tripeptides, the smallest for which the mechanisms to generate [b(2) - 1 + Ag](+) and [b(2) + 17 + Ag](+) products are both operative, we found that in most cases acetylation causes an increase in the abundance of the C-terminal rearrangement ion, [b(2) + 17 + Ag](+), relative to the rival N-terminal rearrangement ion, [b(2) - 1 + Ag](+). The presence of a free amino group to bind to the metal ion significantly influences the relative abundances of the product ions. We propose a mechanism for the formation of the [b(n) + 17 + Ag](+) that is based on the formation of a five-membered oxazolidin-5-one and tetrahedral carbon intermediate that may collapse to a peptide upon release of CO and an imine, aided by the fact that the ring formed during C-terminal rearrangement is both a hemiacylal and hemiaminal. We also identified an influence of amino acid sequence on the relative abundances of the [b(n) + 17 + Ag](+) and [b(n) - 1 + Ag](+) product ions, whereby bulky substituents located on the alpha-carbon of the amino acid to the C-terminal side of the cleavage site apparently promote the formation of the [b(n) + 17 + Ag](+) product over [b(n) - 1 + Ag](+) when the amino acid to the N-terminal side of the cleavage site is glycine. The latter ion is the favored product, however, when the bulky group is positioned on the alpha-carbon of the amino acid to the N-terminal side of the cleavage site.
OBJECTIVES: The purposes of this study were: (1) to ascertain the incidence and nature of severe physical child abuse in Wales; (2) to ascertain the incidence of all physical abuse in babies under 1 year of age; and (3) to determine whether child protection registers (CPR) accurately reflect the numbers of children who are physically abused. METHODS: This is a population-based incidence study based in Wales, UK, for 2 years from April 1996 through March 1998. Children studied were under the age of 14 with severe physical abuse consistent with the criminal law level of Grievous Bodily Harm. This included seven categories of injury (death; head injury including subdural hemorrhage; internal abdominal injury; physical injury in Munchausen Syndrome by Proxy including suffocation; fracture; burn or scald; adult bite). Cases were ascertained by a pediatrician surveillance reporting system (WPSU). A criterion for inclusion was multidisciplinary agreement that physical abuse had occurred (at case conference, strategy meeting, or Part 8 Review). The incidence of all babies under 1 year of age with physical abuse was also studied. Ascertainment of babies under the age of 1 year was undertaken from CPR as well as the WPSU. RESULTS: Severe abuse is six times more common in babies [54/100,000/year (95% CI +/- 17.2)] than in children from 1 year to 4 years of age [9.2/100,000 (95% CI +/- 3.6)]. It is 120 times more common than in 5- to 13-year-olds [0.47/100,000 (95% CI +/- 0.47)]. This is mainly because two types of serious abuse (brain injury including subdural hemorrhage and fractures) are more common in babies under the age of 1 year than older children. Using data from two sources (the WPSU and CPRs), the incidence of physical abuse in babies is 114/100,000 (CI 114 +/- 11.8) per year. This equates to 1 baby in 880 being abused in the first year of life. The largely rural Health Authority area in Wales had incidence figures for abuse in babies that were 50% of the three other predominantly urban Health Authority areas. Boys throughout the series were more at risk of being severely abused than girls (p < .025). Only 29% of the babies under 1 year of age on the CPR had actually been injured. Thirty percent of abused babies under the age of 1 year and 73% of severely abused children over the age of 1 year had caused previous concern to health professionals regarding abuse or neglect. CONCLUSIONS: Physical abuse is a significant problem in babies under the age of 1 year. Very young babies (under 6 months old) have the highest risk of suffering damage or death as a result of physical abuse. Severe abuse, in particular subdural hematoma and fracture, is much more common in babies than in older children. There is evidence of failure of secondary prevention of child abuse by health professionals, with a greater need to act on concerns regarding abuse and neglect. Interagency child protection work in partnership with parents should focus more on protecting babies under age 1 year from further abuse than on maintenance of the infant within an abusive home. The CPR is not intended as an accurate measure of children suffering abuse. It is a record of children requiring a child protection plan and must not be used as a measure of numbers of abused children.
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Human efforts to produce food and energy are changing the nitrogen (N) cycle of the Earth. Many of these changes are highly beneficial for humans, while others are detrimental to people and the environment. These changes transcend scientific disciplines, geographical boundaries, and political structures. They challenge the creative minds of natural and social scientists, economists, engineers, business leaders, and decision makers. The Second International Nitrogen Conference was designed to facilitate communications among all stakeholders in the "nitrogen community" of the world. The Conference participants" goal in the years and decades ahead is to encourage every country to make optimal choices about N management in food production and consumption, energy production and use, and environmental protection. Scientific findings and recommendations for decision makers that emerged from the Conference are presented.
Planning and decision-making can be improved by access to reliable forecasts of ecosystem state, ecosystem services, and natural capital. Availability of new data sets, together with progress in computation and statistics, will increase our ability to forecast ecosystem change. An agenda that would lead toward a capacity to produce, evaluate, and communicate forecasts of critical ecosystem services requires a process that engages scientists and decision-makers. Interdisciplinary linkages are necessary because of the climate and societal controls on ecosystems, the feedbacks involving social change, and the decision-making relevance of forecasts.
A strain of Tetranychus urticae (Koch; Acari: Tetranychidae), collected from hops (Humulus humuli L; Cannabaceae) in England with a short history of tebufenpyrad use, exhibited resistance to four METI (mitochondrial electron transport inhibitor)-acaricides; tebufenpyrad, pyridaben, fenazaquin and fenpyroximate. Resistance factors for these compounds in a microimmersion assay were 46, 346, 168 and 77 respectively, and corresponded to those exhibited by a Japanese METI-acaricide-resistant reference strain. Levels of resistance remained stable without further selection, and selection with tebufenpyrad did not increase them. The UK strain was also resistant (c 6-fold) to bifenthrin. Crosses of homozygous, diploid females with hemizygous, haploid males showed that, in the UK strain, METI-acaricide resistance was paternally and maternally inherited, and was an incompletely dominant trait. Another tebufenpyrad-resistant strain from the UK, originating from a chrysanthemum nursery (Chrysanthemum foeniculaceum Giseke; Asteraceae) was collected eight months later at a site c 210 km distant from the first. These are the first published incidences of METI-acaricide resistance in Europe and implications for the future use of these compounds are discussed.
An automated packed-column semi-preparative supercritical fluid chromatography/mass spectrometry (SFC/MS) system incorporating mass-directed fraction collection has been designed and implemented as an alternative to preparative HPLC and preparative HPLC/MS (PrepLC/MS) for the purification of pharmaceutical compounds. The system incorporates a single quadrupole mass spectrometer and a supercritical fluid chromatograph. Separations were achieved using a binary solvent system consisting of carbon dioxide and methanol. Purification of SFC-separated compounds was achieved incorporating mass-directed fraction collection, enabling selective isolation of the target molecular weight compound and eliminating the collection of undesired compounds (e.g., by-products, excess starting materials, etc.). Cross contamination between fractions and recoveries of the system were investigated. Mass spectrometer ionization with basic mobile additives is discussed, and examples of preparative SFC/MS chiral separations are presented. Early experiences suggest SFC will be a powerful and complementary technique to HPLC for the purification of pharmaceutical compounds.
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This research was to study the in vitro and in vivo development of cloned embryos derived from adult rabbit fibroblasts following various activation protocols. Effects of serum starvation and passage number of donor cells on the efficiency of cloning were also examined. In experiment I, oocytes were activated either by electric pulses or by electric pulses followed by culture with 6-dimethylaminopurin (DMAP). For experiment II, the best activation protocol from experiment I was employed for cloning using adult rabbit fibroblasts that were cultured for 0-15 passages. In experiment III, the effect of serum starvation of the donor cells on cloning was examined. Finally, in experiment IV, embryo transfers were conducted. These experiments showed that combined electrical pulse and DMAP treatment resulted in superior parthenogenetic blastocyst development (up to 29%), and that activation of the cytoplast before versus after fusion was not different in supporting the in vitro development of nuclear transferred embryos (16%-18% blastocysts). Adult fibroblasts derived from nonpassaged cells were less capable of developing into blastocysts than passaged cells (6% vs. 17%). Serum starvation of donor cells improved cleavage (up to 71%) but did not improve blastocyst development (13%), and no progeny was obtained, irrespective of the treatment. Cell-cycle analysis of adult rabbit fibroblast cells showed that passage 6 and 12 cells were more likely to be in G(0)/G(1) than passage 0 cells, which agrees with the improved embryo development in the passaged-cell groups.
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