Clinical use of a rapid collagen binding assay for von Willebrand factor cleaving protease in patients with thrombotic thrombocytopenic purpura

A simple collagen binding assay (CBA) for measuring activity of the von Willebrand factor cleaving protease in clinical samples is described, and results of fifty masked plasmapheresis samples rom patients with TTP/HUS and other diseases are presented. There was 97.5% concordance between the CBA and a multimer gel assay. The CBA identified low protease activity in 78% of patients who had a clinical syndrome consistent with TTP/HUS and in 2 of 10 sick controls, giving it a positive predictive value of 0.94. The heterogeneity regarding the presence or absence of vWF protease activity in patients with TTP/HUS was confirmed by finding a low negative predictive value of 0.50 with the CBA. The CBA detected inhibitors of the protease in 26 of 29 patients (90%) with TTP/HUS and low protease activity levels. The CBA is a useful clinical assay for examining von Willebrand factor protease activity and detecting inhibitors against the protease.     

Iron status, movement disorders, and acute phase response in elderly psychiatric patients.

The previously reported relation between iron deficiency and movement disorders was studied in a population with a high prevalence of both problems. There was no evidence of a direct statistical relation between iron deficiency and movement disorders. Significant associations were, however, found between movement disorders and features of the acute phase response to physiological stress. Indices of iron status are known to be affected by the acute phase response and it is suggested that the previously reported abnormalities in iron status may be secondary to this.     

Oligoclonal bands predict multiple sclerosis in children with optic neuritis

We retrospectively evaluated predictors of conversion to multiple sclerosis (MS) in 357 children with isolated optic neuritis (ON) as a first demyelinating event who had a median follow‐up of 4.0 years. Multiple Cox proportional‐hazards regressions revealed abnormal cranial magnet resonance imaging (cMRI; hazard ratio [HR] = 5.94, 95% confidence interval [CI] = 3.39–10.39, p < 0.001), presence of cerebrospinal fluid immunoglobulin G oligoclonal bands (OCB; HR = 3.69, 95% CI = 2.32–5.86, p < 0.001), and age (HR = 1.08 per year of age, 95% CI = 1.02–1.13, p = 0.003) as independent predictors of conversion, whereas sex and laterality (unilateral vs bilateral) had no influence. Combined cMRI and OCB positivity indicated a 26.84‐fold higher HR for developing MS compared to double negativity (95% CI = 12.26−58.74, p < 0.001). Accordingly, cerebrospinal fluid analysis may supplement cMRI to determine the risk of MS in children with isolated ON. Ann Neurol 2015;77:1076–1082     

The reliability of individual differences in face-selective responses in the fusiform gyrus and their relation to face recognition ability

Face recognition ability varies widely in the normal population and there is increasing interest in linking individual differences in perception to their neural correlates. Such brain-behavior correlations require that both the behavioral measures and the selective BOLD responses be reliable. The reliability of the location of the fusiform face area (FFA) has been demonstrated in several studies. Here, we address reliability of a different kind: reliability of the magnitude of responses to faces within this localized region. We calculated split-half reliability of face-selective responses within functionally defined posterior and anterior face-selective patches in the fusiform gyrus (FFA1/FFA2). We used data from two published studies that included both a functional localizer for face-selective regions and independent data suitable for quantifying face-selectivity. We found highly reliable face selectivity in both hemispheres that was highest in the centermost voxel(s) compared to larger regions of interest. Differences in face-selectivity between the two face patches within one hemisphere and across hemispheres were also reliable. Our results reveal considerable reliability of face-selective signals in and across FFA in adults. Given the good reliability of behavioral measures of face recognition, prior failures to find a relationship between the mean response to faces in FFA and behavioral face recognition in normal adult subjects are unlikely to be due to limitations of the measurements.     

Plasma lipid peroxidation in sporadic Parkinson's disease. Role of the L-dopa

Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, such as Parkinson's disease (PD). There are several methods to measure oxidative stress, being lipid peroxidation (LPO) one of the most frequently used. Endogenous plasma LPO was determined by a spectrofluorimetric method in fifty two patients with sporadic PD and in forty controls. To know the maximum capacity of lipids to peroxidate, LPO was also measured after co-incubation with Fe2+/H2O2 (exogenous LPO). All PD patients were taken L-dopa and the effect of this treatment on LPO levels was additionally studied. Urine catecholamines and their main metabolites were also analyzed, and their possible correlation to LPO statistically studied. Endogenous plasma LPO levels were 33% higher in PD group than in control group (P<0.001). Exogenous plasma or oxidizability was also higher in PD patients compared to controls (20%, P<0.05). The intake of L-dopa was negatively dose-related to endogenous and exogenous plasma LPO. In conclusion, plasma of PD patients has elevated levels of LPO and also is more prone to peroxidation than that in the control group. The results also suggest an antioxidant effect of L-dopa.     

Optical coherence tomography: a quantitative tool to screen for papilledema in craniosynostosis

Purpose

Our aim was to evaluate if optical coherence tomography (OCT) can be used as an alternative for fundoscopy to screen for increased intracranial pressure (ICP) in children with craniosynostosis

Methods

We performed a prospective cohort study at the Dutch Craniofacial Centre. We included 38 patients with nonsyndromic scaphocephaly and Crouzon’s syndrome aged 3–8 years old, in whom we scored complaints suggestive of increased ICP and performed fundoscopy and OCT. Main outcome measures total retinal thickness (TRT) which was measured on 58 OCT scans.

Results

Forty-three percent of fundoscopies revealed pathologic changes of the papil in at least one eye. Retinal thickness was increased in patients with an abnormal fundoscopy as compared to patients with a normal papil (TRT p?<?0.001). Patients with Crouzon’s syndrome had a significantly increased retinal thickness as compared to patients with scaphocephaly (TRT p?<?0.001).

Conclusions

The current study demonstrates that OCT in children with craniosynostosis is feasible. It confirms that retinal thickness increases in case of papilledema. Given the quantitative character, OCT has a high potential as an alternative tool to screen for papilledema in craniosynostosis and other pediatric populations.     

Increased in vitro uptake of the complement C3b in the serum of patients with Guillain-Barré syndrome, myasthenia gravis and dermatomyositis

To examine the role of complement in certain autoimmune neuromuscular diseases, we used an in-vitro quantitative complement uptake assay that allows measurement of the capacity of patients' sera to deposit fragments of the third complement component onto sensitized targets. C3 uptake was significantly higher in patients with active dermatomyositis, Guillain-Barré syndrome and myasthenia gravis, compared to inclusion body myositis and controls. The in-vitro C3 uptake assay supports the role of C3b neoantigen and Membranolytic Attack Complex deposition in the target tissues and may be a useful tool to monitor disease activity in patients with complement-mediated neurological disorders.     

Central actions of CRF on thermogenesis are mediated by pro-opiomelanocortin products

Corticotrophin-releasing factor (CRF) causes central activation of thermogenesis. The aim of this study was to investigate whether this action is mediated by ACTH or other peptides derived from the ACTH precursor pro-opiomelanocortin (POMC) within the CNS. Central (intracerebroventricular) injection of rat CRF caused dose-dependent increases in resting oxygen consumption (VO2) in conscious rats (maximal 26 +/- 5% at 2 nmol CRF). These responses were significantly attenuated by pretreatment (i.c.v.) with either a monoclonal antibody raised to gamma 1MSH or with naloxone which antagonises beta-endorphin (beta-EP) actions. The increases were not affected by pretreatment with monoclonal antibodies to ACTH or the N-terminal of POMC. Central injections of gamma 1-melanocyte-stimulating hormone (MSH) or beta-EP caused dose-dependent increases in VO2 (maximal at 0.5-1.5 pmol) and these were markedly inhibited by pretreatment with the anti-gamma 1-MSH antibody or naloxone respectively. Injection of ACTH or alpha MSH did not significantly affect VO2 at doses up to 2 nmol. These data indicate that the central actions of CRF on thermogenesis may be mediated, at least in part, by release of gamma MSH and/or beta-EP.     

Influence of a calcium dependent protease inhibitor on platelet activation and secretion

Continuous proteolysis resulting in consumption of major cytoskeletal proteins may be essential for platelet activation and aggregation. In this study we evaluated the effect of a known protease inhibitor, Leupeptin, on agonist induced platelet aggregation and secretion. Platelets exposed to 10 ugs/ml of Leupeptin did not aggregate in response to the action of thrombin (0.2u/ml). However, a concentration of Leupeptin as high as 250 ugs/ml did not prevent arachidonate induced aggregation and secretion. Leupeptin (100 ugs/ml) effectively blocked thrombin (0.2 u/ml) induced elevation of cytosolic calcium, but did not affect arachidonate induced elevation of platelet intracellular calcium levels. At a concentration of 100 ug/ml, Leupeptin effectively blocked thrombin (0.5u/ml) induced clot formation of platelet poor plasma, suggesting that it can exert its effect on thrombin by preventing fibrinogen degradation. Effective K_i for the competitive inhibition of thrombin induced hydrolysis of a chromogenic substrate, S2238, by Leupeptin was 2.4 uM. Leupeptin inhibition of platelet function was reversible by washing platelets free of the polypeptide. Results of our study demonstrate that Leupeptin inhibits thrombin induced platelet activation, probably by interfering with its proteolytic activity on the platelet surface membrane. However, inhibition of platelet surface membrane associated proteases did not prevent activation of platelets by other agonists.