Elevated serum biotinidase activity in hepatic glycogen storage disorders-A convenient biomarker

Summary: An elevated serum biotinidase activity in patients with glycogen storage disease (GSD) type Ia has been reported previously. The aim of this work was to investigate the specificity of the phenomenon and thus we expanded the study to other types of hepatic GSDs. Serum biotinidase activity was measured in a total of 68 GSD patients and was compared with that of healthy controls (8.7 ±10; range 7.0-10.6mU/ml; n=6). We found an increased biotinidase activity in patients with GSD Ia (17.7 ±3.9; range: 11.4-24.8; n=21), GSD I non-a (20.9 ±5.6; range 14.6-26.0; n=4), GSD III (12.5 ±-3.6; range 7.8-19.1; n=3), GSD VI (15.4 ±-2.0; range 14.1-17.7; n=) and GSD IX (14.0 ±-3.8; range: 7.5-21.6; n=22). The sensitivity of this test was 100% for patients with GSD Ia, GSD I non-a and GSD VI, 62% for GSD III, and 77% for GSD IX, indicating reduced sensitivity for GSD III and GSD IX, respectively. In addition, we found elevated biotinidase activity in all sera from 5 patients with Fanconi-Bickel Syndrome (15.3 ±-3.7; range 11.0-19.4). Taken together, we propose serum biotinidase as a diagnostic biomarker for hepatic glycogen storage disorder

Hepatitis-B- und -C-assoziierte Glomerulonephritiden

Zusammenfassung: Virale Hepatitiden sind häufig mit extrahepatischen Manifestationen assoziiert. Bei der HepatitisB ist die membranöse Glomerulonephritis (GN) die häufigste histologische Diagnose. Im Rahmen der HepatitisC wird vorwiegend eine membranoproliferative GN mit oder ohne gemischte Kryoglobulinämie beobachtet. Eine zentrale pathogenetische Rolle spielen Immunkomplexe (virale Antigene, antivirale Antikörper, bei Kryoglobulinämie auch Rheumafaktoren). Diese Komplexe werden in der Niere abgelagert und aktivieren Komplement, was schließlich zum Nierenschaden führt. Therapeutisch zentral ist die antivirale Therapie mit dem Ziel der Antigenelimination. Im Falle der HepatitisB kann eine Therapie mit IFNα durchgeführt werden, alternativ mit Lamivudin. Eine immunsuppressive Therapie steht eher im Hintergrund. Bei der HepatitisC ist die Standardtherapie IFNα in Kombination mit Ribavirin. Bei einer zusätzlichen Kryoglobulinämie besteht die Alternative einer Therapie mit Rituximab, bei schwerem Verlauf mit Plasmapherese, Steroiden und Cyclophosphamid. Bei vollständiger Elimination der Virusreplikation ist die Prognose dieser sekundären GN günsti

The abstract boundary---a new approach to singularities of manifolds

A new scheme is proposed for dealing with the problem of singularities in General Relativity. The proposal is, however, much more general than this. It can be used to deal with manifolds of any dimension which are endowed with nothing more than an affine connection, and requires a family \calc\ of curves satisfying a {\em bounded parameter property} to be specified at the outset. All affinely parametrised geodesics are usually included in this family, but different choices of family \calc\ will in general lead to different singularity structures. Our key notion is the {\em abstract boundary\/} or {\em $a$-boundary\/} of a manifold, which is defined for any manifold \calm\ and is independent of both the affine connection and the chosen family \calc\ of curves. The $a$-boundary is made up of equivalence classes of boundary points of \calm\ in all possible open embeddings. It is shown that for a pseudo-Riemannian manifold (\calm,g) with a specified family \calc\ of curves, the abstract boundary points can then be split up into four main categories---regular, points at infinity, unapproachable points and singularities. Precise definitions are also provided for the notions of a {\em removable singularity} and a {\em directional singularity}. The pseudo-Riemannian manifold will be said to be singularity-free if its abstract boundary contains no singularities. The scheme passes a number of tests required of any theory of singularities. For instance, it is shown that all compact manifolds are singularity-free, irrespective of the metric and chosen family \calc.Comment: 40 pages (amslatex) + 5 uuencoded figures (A postscript version is also available on http://einstein.anu.edu.au/), CMA Maths. Research Report No. MRR028-9

Magnetic Moments of the Baryon Decuplet in a Relativistic Quark Model

The magnetic moments of the baryon decuplet are calculated in a relativistic constituent quark model using the light-front formalism. Of particular interest are the magnetic moments of the $\Omega^-$ and $\Delta^{++}$ for which new recent experimental measurements are available. Our calculation for the magnetic moment ratio $\mu(\Delta^{++})/\mu(p)$ is in excellent agreement with the experimental ratio, while our ratio $\mu(\Omega^-)/\mu(\Lambda^0)$ is slightly higher than the experimental ratio.Comment: 10 pages ReVTeX, SLAC-PUB-621

Octet, decuplet and antidecuplet magnetic moments in the chiral quark soliton model revisited

We reanalyse the magnetic moments of the baryon octet, decuplet, and antidecuplet within the framework of the chiral quark-soliton model, with SU(3) symmetry breaking taken into account. We consider the contributions of the mixing of higher representations to the magnetic moment operator arising from the SU(3) symmetry breaking. Dynamical parameters of the model are fixed by experimental data for the magnetic moments of the baryon octet and from the masses of the octet, decuplet and of $\Theta^{+}$. The magnetic moment of $\Theta^{+}$ depends rather strongly on the pion-nucleon sigma term and reads $-1.19 {\rm n.m.}$ to $-0.33 {\rm n.m.}$ for $\Sigma_{\pi N} = 45$ and 75 MeV respectively. The recently reported mass of $\Xi^{--}_{\bar{10}}(1862)$ is compatible with $\Sigma_{\pi N} = 73$ MeV. As a byproduct the strange magnetic moment of the nucleon is obtained with a value of $\mu^{(s)}_N =+0.39$ n.m.Comment: RevTeX is used. 12 pages, 3 figures, final version for publication in Phys. Rev.

Nachweis der Ermüdungssicherheit von Brücken – Teil 1: Veranlassung, Ziel und Messkonzept des Monitoring-Projekts „Bahnbrücke Eglisau"

Durch steigende Anforderungen des modernen Bahnverkehrs (vor allem durch höhere Achslasten und Zugfrequenzen) werden Bahnbrücken immer stärker beansprucht. Entsprechend muss die Trag- und Ermüdungssicherheit dieser Brücken nachgewiesen werden. Dies erfolgt über eine so genannte Aktualisierung, indem die effektiv auftretende Beanspruchung des Brückentragwerks genau ermittelt wird. Im Rahmen eines Pilotprojekts werden zurzeit zerstörungsfreie, statische und dynamische Belastungsversuche an der Bahnbrücke Eglisau, Schweiz, durchgeführt, um Informationen zu erhalten, auf deren Basis zuverlässige Aussagen zur Tragsicherheit und Ermüdungssicherheit gemacht werden sollen. Im laufenden Bahnbetrieb ist die eingleisig befahrene Bahnbrücke schwer zugänglich, weshalb die Langzeitmessungen mit Hilfe eines festinstallierten, vollautomatischen Bauwerk-Monitoring-Systems (swissMon) durchgeführt werden. Mit Hilfe dieses Systems können beliebig viele, unterschiedliche Messsensoren zyklisch oder getriggert durch das Überfahren eines Zuges betrieben werden. Die mit swissMon gewonnen Daten sind eine verlässliche Grundlage für weitere Analysen und Modellrechnungen und unterstützen die beteiligten Tragwerksingenieure insbesondere bei der Beurteilung der Ermüdungssicherhei

Cryptococcus gattii Meningoencephalitis in an Immunocompetent Person 13 Months after Exposure

Abstract : A 53-year old immunocompetent Swiss female is described who developed severe meningoencephalitis due to infection with Cryptococcus gattii 13 months following exposure on Vancouver Island, Canada. Diagnosis was based on cerebrospinal fluid (CSF) examination, i.e., positive India-ink staining, positive latex particle agglutination, and positive culture. Species identification was performed by growth on L-canavanine-glycine-bromthymol blue medium and by sequencing of the intergenic and internal transcribed spacer regions of the rRNA genes. After initial therapy with fluconazole by which the patient did not improve, therapy was changed to amphotericin B and flucytosine and later to high-dose fluconazole and amphotericin B. Despite long-term treatment and external drainage of the CSF, the patient's condition improved only slowly. The patient was discharged after 132 days of hospitalizatio

Characterisation of the mycobacterial NER system reveals novel functions of uvrD1 helicase

In this study, we investigated the role of the nucleotide excision repair (NER) pathway in mycobacterial DNA repair. Mycobacterium smegmatis lacking the NER excinuclease component uvrB, the helicase uvrD1 and a double knock-out lacking both proteins were constructed and their sensitivity to a series of DNA damaging agents wa analysed. As anticipated, the mycobacterial NER system was shown to be involved in the processing of bulky DNA adducts and inter-strand cross-links. In addition, it could be shown to exert a protective effect against oxidising and nitrosating agents. Interestingly, inactivation of uvrB and uvrD1 significantly increased marker integration frequencies in gene conversion assays. This implies that in mycobacteria, which lack the postreplicative mismatch repair system, NER, and particularly the UvrD1 helicase, is involved in the processing of a subset of recombination-associated mismatches

Characterization of fecal nitrogen forms produced by a sheep fed with 15N labeled ryegrass

Little is known about nitrogen (N) forms in ruminant feces, although this information is important to understand N dynamics in agro-ecosystems. We fed 15N labeled ryegrass hay to a sheep and collected 15N labeled feces. Nitrogen forms in the feces were characterized by chemical extractions, solid-state cross polarization 15N nuclear magnetic resonance spectroscopy (SS CP/MAS 15N NMR) and Curie-point pyrolysis-gas chromatography/mass spectrometry (Cp Py-GC/MS). A 4months incubation experiment was conducted to assess N release from the feces. Half of the fecal N could be ascribed to bacterial and endogenous debris and a third to undigested dietary N. About a tenth of the fecal N was mineralized during the incubation experiment. The 15N abundance of nitrate released during the incubation remained constant and close to the 15N abundance of the total feces N. The NMR analysis of the feces showed that most of the N was present in proteins, while some was present as heterocyclic N, amino acids and ammonium. The Cp Py-GC/MS analysis confirmed the presence of proteins, amino acids and heterocyclic N in the feces. Comparing these results to those obtained from the 15N labeled hay suggests that some N compounds present in the plant were not digested by the animal, and that the animal excreted de novo synthesized N compounds. The low content in ammonium and amino acids, the low rate of N release from these feces during the incubation and the relatively high fecal protein content, particularly the hard to mineralize undigested and microbially bound forms, can explain the low transfer of N from these feces to crops observed in a previous wor

Reasons why people in Switzerland seek assisted suicide : the view of patients and physicians

Background: Assisted suicide is permitted in Switzerland provided that assistance is not motivated by selfish reasons. Suicides are commonly performed with the assistance of right-to-die organisations and the use of a lethal dose of barbiturates prescribed by a participating physician. We examined the reasons physicians provided for writing the prescription and the reasons patients gave for requesting assistance in dying. Methods: We analysed all reported cases of assisted suicide that were facilitated by right-to-die organisations between 2001 and 2004 in the city of Zurich, and for which both the medical report and the optional letter written by the decedent providing information on their reasons for seeking assistance in suicide (N = 165). Results: The reasons most often reported by physicians (ph), as well as persons who sought help (p), were: pain (ph: 56% of all assisted suicides, p: 58%), need for long-term care (ph: 37%, p: 39%), neurological symptoms (ph: 35%, p: 32%), immobility (ph: 23%, p: 30%) and dyspnoea (ph: 23%, p: 23%). Control of circumstances over death (ph: 12%, p: 39%); loss of dignity (ph: 6%, p: 38%); weakness (ph: 13%, p: 26%); less able to engage in activities that make life enjoyable (ph: 6%, p: 18%); and insomnia and loss of concentration (ph: 4%, p: 13%) were significantly more often mentioned by decedents than by physicians. Conclusions: Both prescribing physicians and;patients provided with assistance to die quite often mentioned pain and other concerns, many of which were objectively assessable and related to unbearable suffering or unreasonable disability. Concerns referable to autonomy and individual judgement were more often noted by people seeking help than by the prescribing physicians