644 research outputs found

    A controlled crossover trial of fendluramine in autism

    Get PDF
    Introduction: Against a background of variable results achieved by the treatment of childhood autism with dopaminergic agonists or antagonists, and opiate antagonists and mild behavioural improvements achieved following treatment with fenfluramine (Geller et al., 1982; Ritvo et al., 1984 among others) a 12 month double-blind crossover trial of fenfluramine was undertaken. [the d-isomer releases serotonin, the l-isomer modestly blocks dopamine receptors.] Methods: Six female and 14 male children and adolescents with autism were enrolled (median 9y; range 5-17 years of age) in a trial run over a 1 month baseline, 5 months of treatment, 2 months placebo, and 5 months of treatment. Parent diaries were kept. Various tests and rating scales for development, verbal and noverbal abilities along with measures of blood serotonin, urinary catecholamines and auditory event-related potentials (ERPs) were measured at 6-month intervals. Results: a) With fenfluramine treatment children lost weight, blood serotonin decreased by 60% and urinary catecholamine levels fell (25-45%, but dopamine utilization (HVA/DA) increased 2-4-fold. b) Under fenfluramine some autistic subjects improved on measures of cognitive and language function. Two mute subjects began to speak, but for the group overall the improvements did not prove significant. [British Ability Scale, Reynell developmental language and Vineland social maturity scale improvements were significant.] c) Treatment improved early stages of information processing, but impaired later stages as measured in the ERP (i.e. early negative going excitatory vs. later positive going inhibitory response, respectively in 7 patients). The early negativity changes (especially over the right hemisphere) correlated inversely with HVA/DA actvivity. d) Side effects reported included lethargy and irritability.. Conclusions: While individuals showed marked reductions of stereotypies, hyperactivity, and improvements on develepmental and cognitive measures, the absence of clear group-wide effects suggests that fenfluramine would have but a limited place in the management of some patients with autism

    UK informative inventory report (1990 to 2013)

    Get PDF
    This is the 10th Informative Inventory Report (IIR) from the UK National Atmospheric Emissions Inventory (NAEI) Programme. The report is compiled to accompany the UK’s 2015 data submission under the United Nations Economic Commission for Europe (UNECE) Convention on Long-Range Transboundary Air Pollution (CLRTAP) and contains detailed information on annual emission estimates of air quality pollutants by source in the UK from 1990 onwards

    Early treatment with minocycline following stroke in rats improves functional recovery and differentially modifies responses of peri-infarct microglia and astrocytes

    Get PDF
    BACKGROUND: Altered neuronal connectivity in peri-infarct tissue is an important contributor to both the spontaneous recovery of neurological function that commonly develops after stroke and improvements in recovery that have been induced by experimental treatments in animal models. Microglia and astrocytes are primary determinants of the environment in peri-infarct tissue and hence strongly influence the potential for neuronal plasticity. However, the specific roles of these cells and the timing of critical changes in their function are not well understood. Minocycline can protect against ischemic damage and promote recovery. These effects are usually attributed, at least partially, to the ability of this drug to suppress microglial activation. This study tested the ability of minocycline treatment early after stroke to modify reactive responses in microglia and astrocytes and improve recovery. METHODS: Stroke was induced by photothrombosis in the forelimb sensorimotor cortex of Sprague-Dawley rats. Minocycline was administered for 2 days after stroke induction and the effects on forelimb function assessed up to 28 days. The responses of peri-infarct Iba1-positive cells and astrocytes were evaluated using immunohistochemistry and Western blots. RESULTS: Initial characterization showed that the numbers of Iba1-positive microglia and macrophages decreased in peri-infarct tissue at 24 h then increased markedly over the next few days. Morphological changes characteristic of activation were readily apparent by 3 h and increased by 24 h. Minocycline treatment improved the rate of recovery of motor function as measured by a forelimb placing test but did not alter infarct volume. At 3 days, there were only minor effects on core features of peri-infarct microglial reactivity including the morphological changes and increased density of Iba1-positive cells. The treatment caused a decrease of 57% in the small subpopulation of cells that expressed CD68, a marker of phagocytosis. At 7 days, the expression of glial fibrillary acidic protein and vimentin was markedly increased by minocycline treatment, indicating enhanced reactive astrogliosis. CONCLUSIONS: Early post-stroke treatment with minocycline improved recovery but had little effect on key features of microglial activation. Both the decrease in CD68-positive cells and the increased activation of astrogliosis could influence neuronal plasticity and contribute to the improved recovery.Wai Ping Yew, Natalia D. Djukic, Jaya S. P. Jayaseelan, Frederick R. Walker, Karl A. A. Roos, Timothy K. Chataway, Hakan Muyderman and Neil R. Sim

    Multi-Periodic Oscillations in Cepheids and RR Lyrae-Type Stars

    Full text link
    Classical Cepheids and RR Lyrae-type stars are usually considered to be textbook examples of purely radial, strictly periodic pulsators. Not all the variables, however, conform to this simple picture. In this review I discuss different forms of multi-periodicity observed in Cepheids and RR Lyrae stars, including Blazhko effect and various types of radial and nonradial multi-mode oscillations.Comment: Proceedings of the 20th Stellar Pulsation Conference Series: "Impact of new instrumentation & new insights in stellar pulsations", 5-9 September 2011, Granada, Spai

    Height and risk of death among men and women: aetiological implications of associations with cardiorespiratory disease and cancer mortality

    Get PDF
    OBJECTIVES: Height is inversely associated with cardiovascular disease mortality risk and has shown variable associations with cancer incidence and mortality. The interpretation of findings from previous studies has been constrained by data limitations. Associations between height and specific causes of death were investigated in a large general population cohort of men and women from the West of Scotland. DESIGN: Prospective observational study. SETTING: Renfrew and Paisley, in the West of Scotland. SUBJECTS: 7052 men and 8354 women aged 45-64 were recruited into a study in Renfrew and Paisley, in the West of Scotland, between 1972 and 1976. Detailed assessments of cardiovascular disease risk factors, morbidity and socioeconomic circumstances were made at baseline. MAIN OUTCOME MEASURES: Deaths during 20 years of follow up classified into specific causes. RESULTS: Over the follow up period 3347 men and 2638 women died. Height is inversely associated with all cause, coronary heart disease, stroke, and respiratory disease mortality among men and women. Adjustment for socioeconomic position and cardiovascular risk factors had little influence on these associations. Height is strongly associated with forced expiratory volume in one second (FEV1) and adjustment for FEV1 considerably attenuated the association between height and cardiorespiratory mortality. Smoking related cancer mortality is not associated with height. The risk of deaths from cancer unrelated to smoking tended to increase with height, particularly for haematopoietic, colorectal and prostate cancers. Stomach cancer mortality was inversely associated with height. Adjustment for socioeconomic position had little influence on these associations. CONCLUSION: Height serves partly as an indicator of socioeconomic circumstances and nutritional status in childhood and this may underlie the inverse associations between height and adulthood cardiorespiratory mortality. Much of the association between height and cardiorespiratory mortality was accounted for by lung function, which is also partly determined by exposures acting in childhood. The inverse association between height and stomach cancer mortality probably reflects Helicobacter pylori infection in childhood resulting inor being associated withshorter height. The positive associations between height and several cancers unrelated to smoking could reflect the influence of calorie intake during childhood on the risk of these cancers

    The PL calibration for Milky Way Cepheids and its implications for the distance scale

    Full text link
    The rationale behind recent calibrations of the Cepheid PL relation using the Wesenheit formulation is reviewed and reanalyzed, and it is shown that recent conclusions regarding a possible change in slope of the PL relation for short-period and long-period Cepheids are tied to a pathological distribution of HST calibrators within the instability strip. A recalibration of the period-luminosity relation is obtained using Galactic Cepheids in open clusters and groups, the resulting relationship, described by log L/L_sun = 2.415(+-0.035) + 1.148(+-0.044)log P, exhibiting only the moderate scatter expected from color spread within the instability strip. The relationship is confirmed by Cepheids with HST parallaxes, although without the need for Lutz-Kelker corrections, and in general by Cepheids with revised Hipparcos parallaxes, albeit with concerns about the cited precisions of the latter. A Wesenheit formulation of Wv = -2.259(+-0.083) - 4.185(+-0.103)log P for Galactic Cepheids is tested successfully using Cepheids in the inner regions of the galaxy NGC 4258, confirming the independent geometrical distance established for the galaxy from OH masers. Differences between the extinction properties of interstellar and extragalactic dust may yet play an important role in the further calibration of the Cepheid PL relation and its application to the extragalactic distance scale.Comment: Accepted for Publication (Astrophysics & Space Science
    corecore