Why human color vision cannot reliably detect cerebrospinal fluid xanthochromia

Background - Visual assessment of cerebrospinal fluid (CSF) for xanthochromia ( yellow color) is practiced by the majority of laboratories worldwide as a means of diagnosing intracranical bleeds.Methods - Colorimetric and spectrophotometric analysis of CSF samples for recognizing the presence of bilirubin either in low concentrations or in the presence of hemolysed blood.Results - The experiments provide the physiological and colorimetric basis for abandoning visual assessment of CSF for xanthochromia.Conclusion - We strongly recommend relying on spectrophotometry as the analytical method of choice

Spectrophotometry for cerebrospinal fluid pigment analysis

The use of spectrophotometry for the analysis of the cerebrospinal fluid (CSF) is reviewed. The clinically relevant CSF pigments--oxyhemoglobin and bilirubin--are introduced and discussed with regard to clinical differential diagnosis and potentially confounding variables (the four T's: traumatic tap, timing, total protein, and total bilirubin). The practical laboratory aspects of spectrophotometry and automated techniques are presented in the context of analytical and clinical specificity and sensitivity. The perceptual limitations of human color vision are highlighted and the use of visual assessment of the CSF is discouraged in light of recent evidence from a national audit in the United Kingdom. Finally, future perspectives including the need for longitudinal CSF profiling and routine spectrophotometric calibration are outlined

Quantification of neurodegeneration by measurement of brain-specific proteins

Quantification of neurodegeneration in animal models is typically assessed by time-consuming and observer-dependent immunocytochemistry. This study aimed to investigate if newly developed ELISA techniques could provide an observer-independent, cost-effective and time-saving tool for this purpose. Neurofilament heavy chain (NfH(SM135)), astrocytic glial fibrillary acidic protein (GFAP), S100B and ferritin, markers of axonal loss, gliosis, astrocyte activation and microglial activation, respectively, were quantified in the spinal cord homogenates of mice with chronic relapsing experimental allergic encephalomyelitis (CREAE, n=8) and controls (n=7). Levels of GFAP were found to be threefold elevated in CREAE (13 ng/mg protein) when compared to control animals (4.5 ng/mg protein, p<0.001). The inverse was observed for NfH(SM135) (21 ng/mg protein vs. 63 ng/mg protein, p<0.001), ferritin (542 ng/mg protein vs. 858 ng/mg protein, p<0.001) and S100B (786 ng/mg protein vs. 2080 ng/mg protein, N.S.). These findings were confirmed by immunocytochemistry, which demonstrated intense staining for GFAP and decreased staining for NfH(SM135) in CREAE compared to control animals. These findings indicate that axonal loss and gliosis can be estimated biochemically using the newly developed ELISA assays for NfH(SM135) and GFAP. These assays may facilitate the quantification of pathological features involved in neurodegeneration

The new Global Multiple Sclerosis Severity Score (MSSS) correlates with axonal but not glial biomarkers

This study investigated whether the new Global Multiple Sclerosis Severity Scale (MSSS) correlated with cerebrospinal fluid biomarkers for axonal and glial pathology. The MSSS correlated with the phosphorylated neurofilament heavy chain (NfH-SMI35, R=0.44, P=0.016). The degree of neurofilament phosphorylation (ratio NfH-SMI34 to NfH-SMI35) was 8-fold higher in severely (median MSSS 6.5) versus mildly (MSSS 3.2) disabled patients (7.3 versus 0.9, P=0.03). The MSSS may provide a statistically powerful tool for comparing overall disease severity and be useful for validating the biomarker concept in MS

Treatment response in relation to inflammatory and axonal surrogate marker in multiple sclerosis

BACKGROUND: This study aimed to investigate if treatment response could retrospectively be related to inflammatory or axonal pathology as measured by plasma surrogate markers. METHODS: In this 1-year observational study 30 multiple sclerosis (MS) patients with relapsing-remitting disease were treated with intramuscular IFNbeta-1a or subcutaneous IFNbeta-1b. Responders and nonresponders were defined according to clinical and magnetic resonance imaging criteria. The control group consisted of 14 healthy subjects. Plasma levels of surrogate markers for inflammation (nitric oxide metabolites (NOx)), astrocytic activation (S100B) and axonal damage (NfH(SM135)) were measured using standard assays. RESULTS: There were 11 nonresponders and 19 responders to IFNbeta treatment. Median S100B levels were elevated in a higher proportion of treatment responders (63%, 42.9 pg/mL) compared to nonresponders (18%, 11.7 pg/mL, P < 0.05, Fisher's exact test) and controls (0%, 2 pg/mL, P < 0.001). Levels of NOx were found to be more frequently elevated in nonresponders (72%, 39 microM) compared to healthy controls (0%, 37 microM, P < 0.05). Levels of NfH(SM135) were more frequently elevated in responders (58%, 300 pg/mL, P < 0.001) and nonresponders (72%, 500 pg/mL, P < 0.001) compared to controls (0%, 4.5 pg/mL). CONCLUSION: Patients with relapsing-remitting MS who had surrogate marker supported evidence for astrocytic activation responded more frequently to treatment with IFNbeta

Some exact non-vacuum Bianchi VI0 and VII0 instantons

We report some new exact instantons in general relativity. These solutions are K\"ahler and fall into the symmetry classes of Bianchi types VI0 and VII0, with matter content of a stiff fluid. The qualitative behaviour of the solutions is presented, and we compare it to the known results of the corresponding self-dual Bianchi solutions. We also give axisymmetric Bianchi VII0 solutions with an electromagnetic field.Comment: latex, 15 pages with 3 eps figure

(3+3)-Annulation of Carbonyl Ylides with Donor-Acceptor Cyclopropanes: Synergistic Dirhodium(II) and Lewis Acid Catalysis

The first (3+3)-annulation process of donor-acceptor cyclopropanes using synergistic catalysis is reported. The Rh2 (OAc)4 -catalyzed decomposition of diazo carbonyl compounds generated carbonyl ylides in situ. These 1,3-dipoles were converted with donor-acceptor cyclopropanes, activated by Lewis acid catalysis, to afford multiply substituted pyran scaffolds in high yield and diastereoselectivity. Extensive optimization studies enabled access to 9-oxabicyclo[3.3.1]nonan-2-one and 10-oxabicyclo[4.3.1]decen-2-ol cores, exploiting solvent effects on intermediate reactivity

Hyperextended Scalar-Tensor Gravity

We study a general Scalar-Tensor Theory with an arbitrary coupling funtion $\omega (\phi )$ but also an arbitrary dependence of the ``gravitational constant'' $G(\phi )$ in the cases in which either one of them, or both, do not admit an analytical inverse, as in the hyperextended inflationary scenario. We present the full set of field equations and study their cosmological behavior. We show that different scalar-tensor theories can be grouped in classes with the same solution for the scalar field.Comment: latex file, To appear in Physical Review