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    Abstract: Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that provides information on the fiber architecture of the brain by measuring water diffusion. Prior work has shown that neuronal degeneration in Alzheimer's disease (AD) and mild cognitive impairment (MCI) alters this architecture. Since the conversion rate to AD is much higher for MCI patients than for normal healthy people, it is important to identify biomarkers with a predictive value on this conversion. In this study, we applied tract-based spatial statistics (TBSS) on datasets of 15 healthy controls, 15 AD patients, and 17 MCI patients. Of these MCI patients eight remained stable, whereas nine developed AD within the first 12-18 months of follow-up investigations. Analysis using TBSS combined with a maximum likelihood regression with random effects of the fornix, the corpus callosum, and the cingulum identified significant differences between these two types of MCI patients in fractional anisotropy (FA) and radial diffusivity (DR). Thus, DTI reveals Alzheimer-specific changes in those MCI subjects that later convert, although they were clinically identical to the other MCI-patients at the time the data were acquired. This finding could lead to early identification of AD and thereby aid early clinical intervention.
    Type of Publication: Journal article published
    PubMed ID: 22947309
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  • 4
    Keywords: brain ; DIAGNOSIS ; ALZHEIMERS-DISEASE ; PROGRESSION ; MILD COGNITIVE IMPAIRMENT ; REVEALS ; HIPPOCAMPAL VOLUME ; conversion ; PREDICT ; DIFFUSION MRI
    Abstract: Background: Brain atrophy in subjects with mild cognitive impairment (MCI) introduces partial volume effects, limiting the sensitivity of diffusion tensor imaging to white matter microstructural degeneration. Appropriate correction isolates microstructural effects in MCI that might be precursors of Alzheimer's disease (AD). Methods: Forty-eight participants (18 MCI, 15 AD, and 15 healthy controls) had magnetic resonance imaging scans and clinical evaluations at baseline and follow-up after 36 months. Ten MCI subjects were diagnosed with AD at follow-up and eight remained MCI. Free-water (FW) corrected measures on the white matter skeleton were compared between groups. Results: FW corrected radial diffusivity, but not uncorrected radial diffusivity, was increased across the brain of the converted group compared with the nonconverted group (P 〈 .05). The extent of increases was similar to that found comparing AD with controls. Conclusion: Partial volume elimination reveals microstructural alterations preceding dementia. These alterations may prove to be an effective and feasible early biomarker of AD.
    Type of Publication: Journal article published
    PubMed ID: 25035154
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  • 5
    ISSN: 1433-2981
    Keywords: Key words:Blood cell differentiation – Cell-Dyn® 3500 – Flow cytometry – Impedance measurement – Mouse and rat haematology – Reference values
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: The objective of this study was to evaluate the performance of the CELL-DYN® 3500 for rat and mouse blood analysis in a routine environment. The WBC (white blood cells), RBC (red blood cells), PLT (platelets) counts and the WBC differential were determined. In addition, the following aspects were studied: within-run precision, day-to-day precision, bias-free paired difference precision; extended ranges of linearity for RBC, HCT (haematocrit), WBC, PLT; carry-over, the effect of blood ageing, cell stability with different anticoagulants; and the normal ranges, the out of range flagging and some typical pathology cases.  The CELL-DYN® 3500 is a multiparameter flow cytometer which counts and differentiates WBC, based on the principle of multi-angle polarised light scatter separation. RBC and PLT are determined by the impedance method. The WBC count is evaluated by both, optical and impedance methods. Reference methods used were according to the ICSH recommendations on blood cell analysis, including manual counts of WBC and platelets, a centrifugal microhaematocrit method and a haemoglobin measurement by spectrophotometry using the WHO haemoglobin standard. All cell counts were compared with the results obtained by our routine blood cell analyser (Contraves AL820), and the WBC differential was compared with the manual microscopic differentiation of the 400 WBC (200 cells differentiated by two technicians).  The following coefficients of vartiation were obtained: within-run precision was 1.2% and 2.7% for WBC; 1.0% and 1.0% for RBC; 1.3% and 0.9% for haematocrit; 2.1% and 2.7% for platelets (rats and mice respectively). Day-to-day precision was performed using human tri-level control blood, and the CVs were found to be 〈1.7% for WBC, 〈1.4% for RBC, 〈1.2% for haemoglobin and 〈6.3% for platelets.  The following ranges of measurement were found to be linear in the rat: WBC: 0.10–20.20×103/μl; RBC: 0.016–14.3×106/μl; haemoglobin: 0.08–26.8 g/dl; haematocrit: 5.0%–77%; platelets: 14.0–1670.0×103/μl. Equal ranges were observed for mouse blood. Carry-over in rat blood was found to be 0.12% for WBC, 0.05% for RBC, 0.15% for haemoglobin and 0.46% for platelets. In mice, similar carry-over results were obtained. The correlation coefficients (Pearson, correlation coefficient) between the CELL-DYN® 3500 and Contraves AL 820 using linear regression analysis were as follows: 0.988 and 0.997 for WBC; 0.986 and 0.920 for RBC; 0.995 and 0.984 for haemoglobin; 0.958 and 0.85 for haematocrit; 0.958 and 0.963 for platelets, for rats and mice, respectively. Correlation coefficients between the CELL-DYN® 3500 and the manual differential of NEU (neutrophils) and LYM (lymphocytes) were higher than 0.8 in rats and higher than 0.9 in mice. Due to the relatively low absolute counts of MONO (monocytes), EOS (eosinophils) and BASO (basophils), only moderate correlation of methods was found.  The CELL-DYN® 3500 was judged to be reliable, accurate and easy-to-use for counting and identifying normal and most of the pathological blood specimens obtained from mice and rats. By using the CELL-DYN® 3500, the time for blood sample analysis can be shortened significantly and provides extensive opportunities to characterise pathological samples.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Monomeric acrylamide was given to beagles in daily oral doses of 15 mg/kg for 22 days and at 5 mg/kg for 60 days. The animals of the high dose group developed neurological signs consistent with peripheral neuropathy. Electrophysiological measurements on the saphenous nerve revealed abnormal nervous function at the end of the treatment period. Conduction velocity was affected to the greatest extent, followed by absolute refractory period and chronaxy. At 30 days upon cessation of treatment conduction velocity and chronaxy were restored to normal but absolute refractory period remained pathological. At that time the first morphological changes of peripheral nerves were detected. Administration of the 5-mg/kg dose resulted in some disability of gait, lengthening of the absolute refractory period and, in half of the animals, in discrete morphological changes. By contrast, after the oral administration of clioquinol up to 200 mg-kg per day for a one-year period there were no signs of functional nor structural alterations of the nervous system. The beagle dog is considered to be a species well suited to reveal neurotoxicity.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0533
    Keywords: Intoxication ; Dog ; Clioquinol ; 2,5-hexanedione ; Distal axonopathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The central distal axonopathy induced in dogs by the administration of high doses of clioquinol is contrasted with the central-peripheral distal axonopathy precipitated by intoxication with 2,5-hexanedione. Mature, pure-bred Beagle dogs received a daily oral dose of 400 mg/kg of clioquinol for up to 7 months, or 1 ml per animal (approximately corresponding to 110 mg/kg) of 2,5-hexanedione for up to 5 months. Intoxicated and control animals were killed and perfused at monthly intervals, so that the spatial-temporal development of the lesion could be followed and correlated with clinical symptoms. During the treatment, dogs intoxicated with 2,5-hexanedione developed symptoms of peripheral neuropathy consisting of flaccid weakness, muscle atrophy, hind-limb foot-drop and areflexia. By contrast, the dogs surviving clioquinol intoxication exhibited a stiff-legged gait, hyperreflexia but no muscle atrophy. Light and electron microscope examination of central and peripheral nervous tissue from dogs intoxicated with 2,5-hexanedione revealed giant axonal swelling and distal axonal degeneration. By contrast, dogs receiving clioquinol showed a distal axonal degeneration confined to the optic tract and the long spinal cord tracts, without any visible involvement of peripheral nerves.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Guinea-pigs were sensitized with various substances (DNCB, penicillin G, PPL, ethylaminobenzoate, formalin) by the Draize method, the maximization method and the new optimization method (intracutaneous test employing adjuvant). The advantages of the optimization method favouring its adoption as a standard sensitization test are discussed in the light of the results obtained by this method and with the two established tests.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Results of the optimization method and of other methods used to assess contact allergy in laboratory animals were compared with known epidemiological data on the occurrence of hypersensitivity reactions in man. Tests were performed with preservatives {formalin, ethylenediamine and sorbic acid), drugs (penicillin G, benzocaine and sulphathiazole) and other contactants belonging to widely different chemical classes (p-phenylenediamine, triclosan, pyrazole derivatives, nickel and chrome salts, eugenol, isoeugenol and mercaptobenzothiazole). The degree of sensitization achieved in guinea pigs by the optimized procedure (intradermal test with adjuvant combination) and the maximization procedure was invariably superior to that produced by the epidermal method using prior irritation of the site of application. Both the optimized procedure and the maximization test seem to be capable of identifying contact allergens that cause hypersensitivity reactions in as few as t in 10,000 of the human population as a whole. The optimization test merits consideration as a standardized and efficiently predictive procedure.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1600-0536
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Groups of guinea pigs were sensitized with a 0.1% solution of dinitrochlorobenzene (DNCB) by the Draize intracutaneous method, The course of the induction process, the influence of the vehicles used and the extent to which the reactions are amenable to assessment according to objective criteria were examined. The sensitivity of the standardized Draize test was then compared with that of various other sensitization techniques, including:The intracutaneous test with adjuvant (optimization test)The maximization test according to Magnusson & Kligman (1969)The epidermal sensitization testThe epidermal sensitization lest wish prior irritation of the contact site (by croton oil or sodium lauryl sulphate).Comparison of these methods revealed that either the additional application of adjuvant or prior irritation of the contact site augmented the degree of sensitization to DNCR just as greatly as the simultaneous use of adjuvant and prior irritation of the skin, (maximization test.). The improved sensitization methods, and in particular the standardised optimization test, may prove to be of particular value for the study of so-called weak allergens.
    Type of Medium: Electronic Resource
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