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Assessment of attenuation (measured in Hounsfield units, HU) of human coronary plaques was performed using multislice computed tomography (MSCT) in an ex vivo model. In three ex vivo specimens of left coronary arteries in oil, MSCT was performed after intracoronary injection of four solutions of contrast material (400 mgI/ml iomeprol). The four solutions were diluted as follows: 1/infinity, 1/200, 1/80, and 1/20. All scans were performed with the following parameters: slices/collimation 16/0.75 mm, rotation time 375 ms. Each specimen was scored for the presence of atherosclerotic plaques. In each plaque the attenuation was measured in four regions of interest for lumen, plaque (non-calcified thickening of the vessel wall), calcium, and surrounding (oil surrounding the vessel). The results were compared with a one-way analysis of variance test and were correlated with Pearson's test. There were no significant differences in the attenuation of calcium and oil in the four solutions. The mean attenuation in the four solutions for lumen (35+/-10, 91+/-7, 246+/-18, 511+/-89 HU) and plaque (22+/-22, 50+/-26, 107+/-36, 152+/-67 HU) was significantly different between each decreasing dilution (p<0.001). The mean attenuation of lumen and plaque of coronary plaques showed high correlation, while the values were significantly different (r=0.73; p<0.001). Intracoronary attenuation modifies significantly the attenuation of plaques assessed with MSCT.

Attenuation variability (measured in Hounsfield Units, HU) of human coronary plaques using multislice computed tomography (MSCT) was evaluated in an ex vivo model with increasing convolution kernels. MSCT was performed in seven ex vivo left coronary arteries sunk into oil followingthe instillation of saline (1/infinity) and a 1/50 solution of contrast material (400 mgI/ml iomeprol). Scan parameters were: slices/collimation, 16/0.75 mm; rotation time, 375 ms. Four convolution kernels were used: b30f-smooth, b36f-medium smooth, b46f-medium and b60f-sharp. An experienced radiologist scored for the presence of plaques and measured the attenuation in lumen, calcified and noncalcified plaques and the surrounding oil. The results were compared by the ANOVA test and correlated with Pearson's test. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. The mean attenuation values were significantly different between the four filters (p < 0.0001) in each structure with both solutions. After clustering for the filter, all of the noncalcified plaque values (20.8 +/- 39.1, 14.2 +/- 35.8, 14.0 +/- 32.0, 3.2 +/- 32.4 HU with saline; 74.7 +/- 66.6, 68.2 +/- 63.3, 66.3 +/- 66.5, 48.5 +/- 60.0 HU in contrast solution) were significantly different, with the exception of the pair b36f-b46f, for which a moderate-high correlation was generally found. Improved SNRs and CNRs were achieved by b30f and b46f. The use of different convolution filters significantly modifief the attenuation values, while sharper filtering increased the calcified plaque attenuation and reduced the noncalcified plaque attenuation.

Intracoronary ultrasound (ICUS) is often used in studies evaluating new interventional techniques. It is important that quantitative measurements performed with various ICUS imaging equipment and materials are comparable. During evaluation of quantitative coronary ultrasound (QCU) software, it appeared that Boston Scientific Corporation (BSC) 30 MHz catheters connected to a Clearview ultrasound console showed smaller dimensions of an in vitro phantom model than expected. In cooperation with the manufacturer the cause of this underestimation was determined, which is described in this paper, and the QCU software was extended with an adjustment. Evaluation was performed by performing in vitro measurements on a phantom model consisting of four highly accurate steel rings (perfect reflectors) with diameters of 2, 3, 4 and 5 mm. Relative differences (unadjusted) of the phantom were respectively: 15.92, 13.01, 10.10 and 12.23%. After applying the adjustment: -0.96, -1.84, -1.35 and -1.43%. In vivo measurements were performed on 24 randomly selected ICUS studies. These showed differences for not adjusted vs. adjusted measurements of lumen-, vessel- and plaque volumes of -10.1 +/- 1.5, -6.7 +/- 0.9 and -4.4 +/- 0.6%. An off-line adjustment formula was derived and applied on previous numerical QCU output data showing relative differences for lumen- and vessel volumes of 0.36 +/- 0.51 and 0.13 +/- 0.31%. 30 MHz BSC catheters connected to a Clearview ultrasound console underestimate vessel dimensions. This can retrospectively be adjusted within QCU software as well as retrospectively on numerical QCU data using a mathematical model.

Intracoronary ultrasound (ICUS) is often used in studies evaluating new interventional techniques. It is important that quantitative measurements performed with various ICUS imaging equipment and materials are comparable. During evaluation of quantitative coronary ultrasound (QCU) software, it appeared that Boston Scientific Corporation (BSC) 30 MHz catheters connected to a Clearview ultrasound console showed smaller dimensions of an in vitro phantom model than expected. In cooperation with the manufacturer the cause of this underestimation was determined, which is described in this paper, and the QCU software was extended with an adjustment. Evaluation was performed by performing in vitro measurements on a phantom model consisting of four highly accurate steel rings (perfect reflectors) with diameters of 2, 3, 4 and 5 mm. Relative differences (unadjusted) of the phantom were respectively: 15.92, 13.01, 10.10 and 12.23%. After applying the adjustment: -0.96, -1.84, -1.35 and -1.43%. In vivo measurements were performed on 24 randomly selected ICUS studies. These showed differences for not adjusted vs. adjusted measurements of lumen-, vessel- and plaque volumes of -10.1 +/- 1.5, -6.7 +/- 0.9 and -4.4 +/- 0.6%. An off-line adjustment formula was derived and applied on previous numerical QCU output data showing relative differences for lumen- and vessel volumes of 0.36 +/- 0.51 and 0.13 +/- 0.31%. 30 MHz BSC catheters connected to a Clearview ultrasound console underestimate vessel dimensions. This can retrospectively be adjusted within QCU software as well as retrospectively on numerical QCU data using a mathematical model.

Refsum disease is caused by a deficiency of phytanoyl-CoA hydroxylase (PHYH), the first enzyme of the peroxisomal α-oxidation system, resulting in the accumulation of the branched-chain fatty acid phytanic acid. The main clinical symptoms are polyneuropathy, cerebellar ataxia, and retinitis pigmentosa. To study the pathogenesis of Refsum disease, we generated and characterized a Phyh knockout mouse. We studied the pathological effects of phytanic acid accumulation in Phyh⁻/⁻ mice fed a diet supplemented with phytol, the precursor of phytanic acid. Phytanic acid accumulation caused a reduction in body weight, hepatic steatosis, and testicular atrophy with loss of spermatogonia. Phenotype assessment using the SHIRPA protocol and subsequent automated gait analysis using the CatWalk system revealed unsteady gait with strongly reduced paw print area for both fore- and hindpaws and reduced base of support for the hindpaws. Histochemical analyses in the CNS showed astrocytosis and up-regulation of calcium-binding proteins. In addition, a loss of Purkinje cells in the cerebellum was observed. No demyelination was present in the CNS. Motor nerve conduction velocity measurements revealed a peripheral neuropathy. Our results show that, in the mouse, high phytanic acid levels cause a peripheral neuropathy and ataxia with loss of Purkinje cells. These findings provide important insights in the pathophysiology of Refsum disease.

In this randomized trial, HIV-positive adults with tuberculous meningitis were assigned to receive 6 to 8 weeks of dexamethasone or placebo in addition to tuberculosis treatment. No benefit of dexamethasone was observed.

The Basso, Beattie and Bresnahan (BBB) locomotor rating scale is the most widely used open field test and has been accepted as a valid way to assess locomotor function after spinal cord contusion injury in the rat. A limitation within the BBB locomotor rating scale is the correct assessment of forelimb (FL)–hindlimb (HL) coordination. This limitation can have major implications for the final assessment of locomotor function. In the present study, we show an objective method to assess coordination based on the regularity index (RI), achieved through the use of the CatWalk method. The RI grades the degree of coordination as the result of the number of normal step sequence patterns multiplied by four and divided by the total amount of paw placements. Using the RI, single walkway crossings can be objectively analyzed on coordination. Integration of the CatWalk based coordination into the BBB scale indicates that objective analysis of coordination results in reliable and more sensitive assessment of locomotor function. This new method has been tested successfully in determination of positive effects of enriched housing on functional recovery after spinal cord injury(SCI).

Background:  Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Co-infection with HIV increases the risk of developing TBM, complicates treatment, and substantially worsens outcome. Whether corticosteroids confer a survival benefit in HIV-infected patients with TBM remains uncertain. Hepatitis is the most common drug-induced serious adverse event associated with anti-tuberculosis treatment, occurring in 20% of HIV-infected patients. The suggested concentration thresholds for stopping anti-tuberculosis drugs are not evidence-based. This study aims to determine whether dexamethasone is a safe and effective addition to the first 6-8 weeks of anti-tuberculosis treatment of TBM in patients with HIV, and investigate alternative management strategies in a subset of patients who develop drug induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy.  Methods:  We will perform a parallel group, randomised (1:1), double blind, placebo-controlled multi-centre Phase III trial, comparing the effect of dexamethasone versus placebo on overall survival in HIV-infected patients with TBM, in addition to standard anti-tuberculosis and antiretroviral treatment. The trial will be set in two hospitals in Ho Chi Minh City, Vietnam, and two hospitals in Jakarta, Indonesia. The trial will enrol 520 HIV-infected adults. An ancillary study will perform a randomised comparison of three DILI management strategies with the aim of demonstrating which strategy results in the least interruption in rifampicin and isoniazid treatment. An identical ancillary study will also be performed in the linked randomised controlled trial of dexamethasone in HIV-uninfected adults with TBM stratified by LTA4H genotype (LAST ACT).  Discussion:  Whether corticosteroids confer a survival benefit in HIV-infected patients remains uncertain, and the current evidence base for using corticosteroids in this context is limited. Interruptions in anti-tuberculosis chemotherapy is a risk factor for death from TBM. Alternative management strategies in DILI may allow the safe continuation of rifampicin and isoniazid therapy.

Environmental enrichment (EE) is a way to induce voluntary locomotor training that positively affects locomotor recovery after acute spinal cord injury (SCI). The beneficial effect on SCI outcome is thought to be based on enhanced plasticity in motor pathways, triggered by locomotor-specific sensory feedback to the spinal cord circuitry for locomotion (central pattern generators [CPGs]). In view of chronic SCI, we tested the hypothesis that EE improves motor outcome after SCI in the rat when started after a clinically relevant delay of 3 weeks. At the CPG level (i.e., the spinal L1–L2 level), where EE-related sensory feedback is processed, two key mechanisms of anatomical plasticity were examined: (1) serotonergic innervation, and (2) survival and differentiation of spinal cord progenitor cells. Delayed EE improved interlimb coordination, which was associated with an increased serotonergic innervation of the ventro-lateral grey matter within the L1–L2 segments. Although spinal cord progenitor cells were found to differentiate into both neurons and glial cells, EE did not affect their survival. These results show that EE induces a substantial improvement of motor outcome after SCI when commenced after a clinically-relevant delay. Increased serotonergic innervation of the lumbar CPG area is therefore suggested to play an important role in the EE-induced recovery of interlimb coordination.

Human immunodeficiency virus (HIV) RNA testing and HIV drug resistance (HIVDR) testing are not routinely available for therapeutic monitoring of patients receiving antiretroviral therapy (ART) in resource-limited settings. World Health Organization HIVDR early warning indicators (EWIs) assess ART site factors known to favor the emergence of HIVDR. HIV drug resistance EWI monitoring was performed within the PharmAccess African Studies to Evaluate Resistance Monitoring (PASER-M) study, comprising 13 ART sites in 6 African countries. Early warning indicator assessment in the PASER network identified vulnerable aspects of ART programs and triggered interventions aimed at minimizing HIVDR emergence. Additionally, data suggest an advantage of medication possession ratio over on-time antiretroviral drug pickup in identifying patients at risk for HIVDR development.