99 research outputs found

    Hypertonic saline test for the investigation of posterior pituitary function

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    The hypertonic saline test is a useful technique for distinguishing partial diabetes insipidus from psychogenic polydipsia, and for the diagnosis of complex disorders of osmoreceptor and posterior pituitary function. However, there is little information concerning its use in childhood. The experience of using this test in five children (11 months to 18 years) who presented diagnostic problems is reported. In two patients, in whom water deprivation tests were equivocal or impractical, an inappropriately low antidiuretic hormone (ADH) concentration ( 295 mosmol/kg). In two children--one presenting with adipsic hypernatraemia and the other with hyponatraemia complicating desmopressin treatment of partial diabetes insipidus--defects of osmoreceptor function were identified. Confirming a diagnosis of idiopathic syndrome of inappropriate ADH secretion (SIADH) was possible in a patient with no other evidence of pituitary dysfunction. The hypertonic saline test was well tolerated, easy to perform, and diagnostic in all cases

    "Test me and treat me" - attitudes to vitamin D deficiency and supplementation: a qualitative study

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    © 2015 BMJ Open, "Test me and treat me"-attitudes to vitamin D deficiency and supplementation: a qualitative study. This manuscript version is made available under the Creative Commons Attribution Licens

    Concert recording 2015-04-16

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    [00:00]. Exultate / Giovanni Gabrielli ; translated by V. Reynolds -- [03:01]. Only begotten son (Hymn of Justinian) / Alexander Gretchaninoff ; translated by D. Calhoun -- [06:00]. Hansel and Gretel (chorale prelude) / Engelbert Humperdinck ; Arr. J. Kirschen -- [09:00]. Chasing Diana / John Cheetham -- [12:50]. Fleurs melodiques des Alpes, no. 6 / Franz Liszt ; translated by H. Jeurissen -- [16:33]. Sextet for horns / Gregory Kerkorian -- [19:32]. Rocky road rag / Lewis Songer -- [21:56]. I saw three ships (traditional English Christmas carol) / arranged by Matt Land

    Cellular responses of Candida albicans to phagocytosis and the extracellular activities of neutrophils are critical to counteract carbohydrate starvation, oxidative and nitrosative stress

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    Acknowledgments We thank Alexander Johnson (yhb1D/D), Karl Kuchler (sodD/D mutants), Janet Quinn (hog1D/D, hog1/cap1D/D, trx1D/D) and Peter Staib (ssu1D/D) for providing mutant strains. We acknowledge helpful discussions with our colleagues from the Microbial Pathogenicity Mechanisms Department, Fungal Septomics and the Microbial Biochemistry and Physiology Research Group at the Hans Kno¨ll Institute (HKI), specially Ilse D. Jacobsen, Duncan Wilson, Sascha Brunke, Lydia Kasper, Franziska Gerwien, Sea´na Duggan, Katrin Haupt, Kerstin Hu¨nniger, and Matthias Brock, as well as from our partners in the FINSysB Network. Author Contributions Conceived and designed the experiments: PM HW IMB AJPB OK BH. Performed the experiments: PM CD HW. Analyzed the data: PM HW IMB AJPB OK BH. Wrote the paper: PM HW OK AJPB BH.Peer reviewe

    RESTORATION OF MOTOR AND NON-MOTOR FUNCTIONS BY NEUROTROPHIC FACTORS IN NONHUMAN PRIMATES WITH DOPAMINE DEPLETION

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    Parkinson’s disease (PD) is a progressive debilitating neurodegenerative disorder characterized by resting tremor, rigidity, bradykinesia and postural instability. As the disease progresses there is a loss of dopamine (DA) neurons in the substantia nigra projecting to the various forebrain and sub-cortical regions. Current treatments for PD are unable to prevent or curtail the neurodegenerative process; so rescuing remaining dopamine in the mid-brain has been the recent focus of research examining the effectiveness of neurotrophic factors (NTFs) in the treatment of PD. In this dissertation, the ability of three novel, recently discovered NTFs to restore DA neurons and motor function in a nonhuman primate model of PD was examined. The NTFs were Cerebral Dopamine Neurotrophic Factor (CDNF) and two variants of Neurturin (NRTN), N2 and N4, that have mutations that prevent binding to heparin sulfate binding sites in the brain. These studies used the unilateral low dose (0.15 ± 0.001 mg/kg) monkey 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD to cause loss of DA neurons. Six groups of monkeys were studied: vehicle-treated (negative control), Glial Cell-line Derived Neurotropic Factor (GDNF, positive control), two groups of CDNF-treated monkeys (450 μg and 150 μg), and N2 and N4-treated groups. After MPTP, monkeys developed moderate symptoms of PD (PD rating scale score=7.9±0.5 on a scale of 0-22, p<0.001), motor dysfunction and increased daytime sleepiness. After three months of infusions, all three NTFs (150 μg CDNF, N2 and N4) significantly increased the number of DA neurons in the substantia nigra, p=0.03, and improved parkinsonian symptoms measured by rating scale, p<0.001. Most motor functions were significantly correlated with the number of DA neurons in the substantia nigra. N4 significantly improved daytime sleep duration, bouts and wake-latency (p=0.02, p=0.06 and p=0.02, respectively). In summary, CDNF, N2 and N4 trophic factors are neurorestorative to DA neurons, motor function is tightly correlated with DA neuronal number, and N4 improved the non-motor symptom of increased daytime sleepiness in this monkey PD model. These factors hold promise for clinical therapy for PD patients

    Retinitis Pigmentosa GTPase Regulator (RPGR) protein isoforms in mammalian retina:insights into X-linked Retinitis Pigmentosa and associated ciliopathies

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    Mutations in the cilia-centrosomal protein Retinitis Pigmentosa GTPase Regulator (RPGR) are a frequent cause of retinal degeneration. The RPGR gene undergoes complex alternative splicing and encodes multiple protein isoforms. To elucidate the function of major RPGR isoforms (RPGR 1-19 and RPGR ORF15), we have generated isoform-specific antibodies and examined their expression and localization in the retina. Using sucrose-gradient centrifugation, immunofluorescence and co-immunoprecipitation methods, we show that RPGR isoforms localize to distinct sub-cellular compartments in mammalian photoreceptors and associate with a number of cilia-centrosomal proteins. The RCC1-like domain of RPGR, which is present in all major RPGR isoforms, is sufficient to target it to the cilia and centrosomes in cultured cells. Our findings indicate that multiple isotypes of RPGR may perform overlapping yet somewhat distinct transport-related functions in photoreceptors

    Application of the Potthoff-Whittinghill technique to detecting temporal clustering of diagnoses of type 1 diabetes at ages 0–14 years in Northumberland, Newcastle upon Tyne and North Tyneside during 1990–2007 inclusive.

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    <p>Notes:</p>a<p>PW is the one-step estimate of β, the extra-Poisson variation, calculated as S/i(0) in the notation of Muirhead <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060489#pone.0060489-Muirhead1" target="_blank">[22]</a>.</p>b<p>SE is the standard error of PW in the absence of extra-Poisson variation, calculated as 1/√i(0) in the notation of Muirhead <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060489#pone.0060489-Muirhead1" target="_blank">[22]</a>.</p>c<p>p-values have been calculated using 10000 simulations of PW, assuming Poisson variation. All p-values are one-sided.</p>d<p>The analysis between years was based on all 526 cases, whereas the other analyses excluded the 58 cases with a diagnosis date of 1<sup>st</sup> July.</p

    A.W.N. Pugin's English residential architecture in its context

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    This Dissertation investigates all of A.W.N. Pugin’s known English residential architecture for the first time, placing it in the context of the domestic and institutional architecture of comparable small buildings, particularly Anglican parsonages, of the period in which he lived and worked. The Dissertation is preceded by a summary of the theoretical issues that architects were addressing from the beginning of the nineteenth century, in particular those which Pugin was later to make a central part of his own theoretical writings. Following an examination of the conventions of the domestic architecture of the period, the Dissertation analyses Pugin’s own buildings, primarily categorising them by plan type. Pugin’s attitude to the orientation, location and landscape of his work is then considered, followed by an analysis of his preferred building forms, their materials, their detailing, and their decoration. In addition, the Dissertation investigates the extent to which Pugin’s architecture was actually historicist, reviving English or Continental Gothic forms and details. The Dissertation further investigates Pugin’s professional practice as a domestic architect, defining the nature of his partnership with his favoured building contractor, George Myers, in the context of contemporary contracting practice. The practical problems of Pugin’s constructions, and the character of his professional relationship with his clients are also assessed. The thesis proposes that elements of Pugin’s architectural theory existed previous to his career amongst English architectural writers and critics, but that medium and small houses designed between 1800 and the mid-1840s were overwhelmingly based on a limited number of conventionalised plans. It will show that Pugin’s residential planning was inherently different from that of these conventional buildings, and that it is classifiable into a number of distinct categories. This thesis furthermore argues that Pugin’s residential architecture was often far from functional and was not essentially historicist. This thesis will show that the planning of medium and small houses changed radically from the 1840s, incorporating aspects of planning which Pugin had pioneered; a conclusion suggests to what extent Pugin’s architectural creativity was expressive of cultural change and preoccupation beyond the realm of architecture. An Appendix is attached which summarises the chronology of all of Pugin’s known residential works
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