Static Markers Research Articles

Specific Antinuclear Antibody Level Changes after B Cell Depletion Therapy in Systemic Sclerosis Are Associated with Improvement of Skin Thickening

To the Editor: B cell depletion therapy using rituximab (RTX) has emerged as a promising therapy in systemic sclerosis (SSc). Our group reported a clinical benefit on skin thickening when RTX (2 × 1000 mg) in combination with methylprednisolone (100 mg) was administered at months 0 and 61. The rationale behind the use of B cell depletion in SSc treatment is based on the growing evidence that B cells play a role in the pathogenesis of the disease2,3. In addition, SSc-associated antinuclear antibody (ANA) are present in the majority of patients, but are generally accepted to be rather static markers, primarily important in diagnosis rather than in followup4. Moreover, conflicting results have been published5 on the change in disease-specific ANA titers in relation to clinical response in other connective diseases (e.g., systemic lupus erythematosus and rheumatoid arthritis) after RTX. To our knowledge, no studies in SSc are available documenting the longterm effect of RTX on these autoantibody levels. In this letter we report the 2-year serologic followup data (months 0, 3, 6, 12, 15, 18, and 24) on the same 8 patients with SSc with diffuse skin involvement (dcSSc) who were included in our initial RTX studies1,6. The idea was to evaluate the relationship between SSc-ANA level changes and clinical response. To document this latter relationship, we performed … Address correspondence to C. Bonroy, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital 2P8, De Pintelaan 185, B-9000, Ghent, Belgium. E-mail: carolien.bonroy{at}uzgent.be

Re: Development of a next-generation tissue valve using a glutaraldehyde-fixed porcine aortic valve treated with decellularization, α-galactosidase, space filler, organic solvent and detoxification

procedure could be very useful to produce new long-lasting heart valves, maybe even usable in younger patients. Finally, an intriguing challenge will be to identify biomarkers able to follow and predict valve durability, as well as to identify very early signs of valve failure. Now, we know that biomarkers, depending on their capacity to change over time, can be easily classified into: (i) static markers, which do not change over time and are almost synonymous with genetic markers and (ii) dynamic markers, which change over time. Both static and dynamic markers can be useful in the identification of valve degeneration. Dynamic biomarkers could monitor the status of the valves with a simple blood test performed periodically, whereas static markers could be used to identify patients susceptible to fast prosthesis degradation. In the near future, we expect to see interesting results coming from the collaboration of researchers and clinicians in this very important translational approach to bioprosthetic valve degeneration.

WE-G-BRF-02: Geometrical Verification of Real-Time Tumor Tracking Using Fast MV Fluoroscopy On a New Generation EPID: Investigating the Influence of Pulsing Artifacts and Artifact Suppression Techniques On Fiducial Marker and Marker-Less Soft-Tissue Detec

Purpose: to investigate the influence of megavolt (MV) pulse artifacts and pulsing artifact suppression techniques on fiducial marker and marker-less detection success for verification of real-time tumor tracking (RTTT) on a gimbaled linac system using fast MV fluoroscopy. Methods: Because frame rates on current clinical available EPIDs is limited to 7.5 Hz, a new generation EPID (XRD-1642 AP19) with a maximum frame rate of 30 Hz was evaluated for RTTT verification. Both 0.5 mm and 0.75 mm Visicoil™ markers were used for MV marker tracking with a frame rate of respectively 7.5 Hz, 15 Hz and 30 Hz. Additionally, marker-less tumor tracking was conducted and compared with the ground-truth fiducial marker motion. Static markers under influence of increasing phantom thickness and dynamic (sine and human irregular) motion was used to investigate performance of MV target detection.For each MV sequence, the free running (FR-nF) (ignoring MV pulsing during readout) acquisition mode was compared with two acquisition modes aiming to reduce MV pulsing artifacts, i.e. combined wavelet-FFT filtering (FR-wF) and a hardware synchronized (S-nF) readout with respect to the MV pulses. Results: For a 0.75 mm visicoil, deviations of sine wave motion were sub-millimeter (RMSE 3 mm, while for MV fluoroscopy in S-mode RMSE <1.0 mm for 15 Hz and RMSE <1.6 mm for 30 Hz. Conclusion: In general, marker contrast was decreased in function of higher frame rates. For a sufficient marker thickness, highest detection success was obtained, even during fast breathing motion, with a frame rate of 30 Hz. Furthermore, a synchronized readout provided most accurate detection of a marker-less soft-tissue structure during RTTT, while 0.75 mm Visicoils were not influenced by pulsing artifacts. Research was sponsored by the Flemish Government through Hercules Foundation and corporate funding from BrainLab AG. Testing equipment was received through a loaner agreement with PerkinElmer Optoelectronics (Germany) and the support of Mitsubishi Heavy Industries.

A novel estimate of endothelial cell autophagic flux is associated with greater vascular endothelial function and reduced oxidative stress in healthy middle‐aged/older adults (855.3)

Using only indirect, static markers of the dynamic cellular quality control system, autophagy, we have reported impaired autophagy in biopsied vascular endothelial cells (EC) of humans with aging that is related to endothelial dysfunction, as indicated by reduced endothelium‐dependent dilation (EDD), and oxidative stress. Here, we estimated dynamic autophagic flux in EC from 10 healthy adults aged 51‐73 by calculating the within‐subject difference in the expression of microtubule‐associated protein light chain 3 (LC3 ratio) between ECs incubated in the absence vs. presence of chloroquine (50 μM 1.5 hrs) to inhibit autophagy. EDD was assessed by: 1) brachial artery flow‐mediated dilation (FMD); and 2) forearm blood flow (FBF) to incremental brachial artery infusions of acetylcholine. Oxidative stress‐suppression of EDD was determined by ∆FBF to co‐infusion of vitamin C (vitC). The LC3 ratio was positively related to FMD (r=0.76, P&lt;0.05) and FBF (r=0.56, P&lt;0.05), but not endothelium‐independent dilation to NO donors (both P&gt;0.05). The LC3 ratio also was inversely related to ∆FBF with vitC (r=‐0.57, P&lt;0.05). These findings provide novel evidence that greater EC autophagic flux is associated with improved endothelial function linked to reduced oxidative stress in healthy middle‐aged/older adults.Grant Funding Source: NIH AG044031 TR001082 AG013038

Improving the Generic Camera Calibration technique by an extended model of calibration display

Generic camera calibration is a method to characterize vision sensors by describing a line of sight for every single pixel. This procedure frees the calibration process from the restriction to pinhole-like optics that arises in the common photogrammetric camera models. Generic camera calibration also enables the calibration of high-frequency distortions, which is beneficial for high-precision measurement systems. The calibration process is as follows: To collect sufficient data for calculating a line of sight for each pixel, active grids are used as calibration reference rather than static markers such as corners of chessboard patterns. A common implementation of active grids are sinusoidal fringes presented on a flat TFT display. So far, the displays have always been treated as ideally flat. In this work we propose new and more sophisticated models to account for additional properties of the active grid display: The refraction of light in the glass cover is taken into account as well as a possible deviation of the top surface from absolute flatness. To examine the effectiveness of the new models, an example fringe projection measurement system is characterized with the resulting calibration methods and with the original generic camera calibration. Evaluating measurements using the different calibration methods shows that the extended display model substantially improves the uncertainty of the measurement system.

MOSHFIT: Algorithms for occlusion-tolerant mean shape and rigid motion from 3D movement data

This work addresses the use of 3D point data to measure rigid motions, in the presence of occlusion and without reference to a prior model of relative point locations. This is a problem where cluster-based measurement techniques are used (e.g. for measuring limb movements) and no static calibration trial is available. The same problem arises when performing the task known as roving capture, in which a mobile 3D movement analysis system is moved through a volume with static markers in unknown locations and the ego-motion of the system is required in order to understand biomechanical activity in the environment. To provide a solution for both of these applications, the new concept of a visibility graph is introduced, and is combined with a generalised procrustes method adapted from ones used by the biological shape statistics and computer graphics communities. Recent results on shape space manifolds are applied to show sufficient conditions for convergence to unique solution. Algorithm source code is available and referenced here. Processing speed and rate of convergence are demonstrated using simulated data. Positional and angular accuracy are shown to be equivalent to approaches which require full calibration, to within a small fraction of input resolution. Typical processing times for sub-micron convergence are found to be fractions of a second, so the method is suitable for workflows where there may be time pressure such as in sports science and clinical analysis.

The Flexible Territoriality of Borders

To what extent do boundaries shape state-centred scales of discourse and action? In an attempt to answer this question, the article delves into one of the key ambiguities characterising boundaries: their being both static markers of sovereign jurisdictions and socially produced and reproduced institutions. Drawing on Foucauldian notions of ‘productive power’, and taking as a referent the Durand Line, the paper elaborates upon Robert Sack's contribution, and proposes an analytical framework that simultaneously captures, while maintaining distinct, two dimensions of territoriality: territoriality as a strategy operating in a socially emptiable space, and territoriality as it unfolds in its actuality. It argues that such framework provides insights on the multi-scalar and place-specific power relations that define the social context in which the Durand Line unfolds, offering important tools for the assessment of boundaries' role in the reproduction of society's contradictions and inequalities. The flexible territoriality of the Durand Line is defined by its simultaneous, and more or less successful, attempt at ordering space across multiple dimensions .

SU-E-T-506: Low Dose Fluoroscopy Based Detection of Implanted Marker Position on the VERO System for Real-Time Tumor Tracking

Purpose: To determine the balance between kV fluoroscopy imaging dose and image quality, for robust detection of implanted fiducial markers in lung on the VERO real-time tumor tracking system. Methods: Tumor visibility in fluoroscopic images can be improved with an implanted fiducial marker in or near the tumor. In total 5 types of fiducial markers were used in this study: solid gold markers, helical coils, multi-gold-marker assemblies, spherical markers and stent-like markers. To investigate automatic detection performance of markers projected on high density structures in the thorax images, an anthropomorphic phantom was placed on a moving platform behind the static markers. Images were acquired with variable imaging settings and in different anatomical circumstances. A marker detection algorithm was developed using maximization of normalized cross correlation with a template library incorporating marker rotations. The templates were created from a 3D model of the marker. The marker detection was applied on 25 images per sequence and detection scores calculated. Additionally imaging dose TLD measurements were conducted for different imaging settings. Results: Differences were seen in the marker detection for different marker types in the different anatomical situations. Beside the intrinsic attenuation of the marker, also its spatial structure played a role. Increasing the mAs did not always increase detection scores. For 0.5 mAs, 100kVp and an SSD of 900mm a skin dose was measure of 0.031 mGy/image and an exit dose of 0.001 mGy/image. At a frame rate of 14 frames/sec this would mean an imaging skin dose of 26.04 mGy/min. Conclusions: It is feasible to use marker-based fluoroscopy based real-time tracking with imaging doses comparable to CBCT. Markers with more elaborate structures made from high density materials have, beside an advantage of being less prone to migration, also an advantage in terms of detectability. This collaborative work was supported by the Flemish government through the Hercules foundation and the “Fonds voor Wetenschappelijk Onderzoek - Vlaanderen” grants G.0486.06 and G.0412.08, and corporate funding from BrainLab AG. There are no other conflicts of interest.

ARSC: Augmented reality student card

Augmented Reality (AR) is the technology of adding virtual objects to real scenes through enabling the addition of missing information in real life. As the lack of resources is a problem that can be solved through AR, this paper presents and explains the usage of AR technology we introduce Augmented Reality Student Card (ARSC) as an application of AR in the field of education. ARSC uses single static markers combined in one card for assigning different objects, while leaving the choice to the computer application for minimizing the tracking process. ARSC is designed to be a useful low cost solution for serving the education field. ARSC can represent any lesson in a 3D format that helps students to visualize different learning objects, interact with theories and deal with the information in a totally new, effective, and interactive way. ARSC can be used in offline, online and game applications with seven markers, four of them are used as a joystick game controller. One of the novelties in this paper is that experimental tests had been made for the ARTag marker set for sorting them according to their efficiency. The results of those tests were used in this research to choose the most efficient markers for ARSC, and can be used for further research. The experimental work in this paper also shows the constraints for marker creation for an AR application. As we need to work in both online and offline application, merging of toolkits and libraries has been made, as presented in this paper. ARSC was examined by a number of students of both genders with average age between 10 and 17 years and it found great acceptance among them.

Inhaled Fluticasone and the Hormonal and Inflammatory Response to Brief Exercise

Inhaled corticosteroids (ICS) improve symptoms in lung diseases, such as asthma. Initial data suggest that the effects of ICS remain localized in the lung; however, recent studies demonstrate alteration to the peripheral immune system in patients with asthma. We sought to evaluate the effect of ICS on peripheral immune mediators and hypothalamic-pituitary-adrenal axis and their response to exercise in healthy men. Eleven healthy males (18-30 yr old) were placed on 2 wk of fluticasone proprionate (440 μg) twice daily. A 30-min bout of exercise was performed on a cycle ergometer at approximately 70% of peak work rate before and after the start of ICS. Blood was sampled before and after exercise. Cytokines and hypothalamic-pituitary-adrenal axis mediators were measured by ELISA, and fluticasone was measured by liquid chromatography/tandem mass spectrometry. After ICS treatment, cortisol and adrenocorticotropin were decreased, and a blunted exercise response was observed for cortisol, adrenocorticotropin, and growth hormone. Peripheral leukocytes and neutrophils were significantly increased in response to exercise in both the untreated and the ICS-treated conditions and at baseline after ICS treatment. Interleukin-6 was elevated with ICS treatment, but the exercise response was blunted. Circulating median fluticasone levels were 0.15 ng·mL(-1) and were increased to 0.20 ng·mL(-1) in response to exercise. Exercise revealed deficits in growth hormone production after ICS treatment not identified by static markers. Neutrophils were shown to be surrogate markers of the systemic effect of ICS. Exercise significantly increased circulating levels of fluticasone. Exercise challenge tests can be used to assess the physiological effect of exogenous corticosteroids.

Effect of Two Weeks of Inhaled Fluticasone on the Hormonal and Inflammatory Response to Brief Exercise in Healthy Young Men

RATIONALE: Inhaled corticosteroids (ICS) improve lung disorders, such as asthma, by altering the immune system. Initial data suggest ICS effects remain localized to the lung; however, recent studies demonstrate alteration to the peripheral immune system in patients with asthma. We evaluated the effect of ICS on peripheral immune mediators and HPA axis, and their response to exercise, in healthy adult males.METHODS: Eleven healthy males (age 18-30 years old) were placed on 2 weeks of Fluticasone proprionate (440 mcg) twice daily. A 30 minute bout of exercise was performed on a cycle ergometer at about 70% peak work rate before and after the start of ICS. Blood was sampled pre- and end-exercise. Cytokines and HPA axis mediators were measured by ELISA and fluticasone by liquid chromatography/tandem mass spectrometry.RESULTS: After ICS-treatment, cortisol and ACTH were decreased and a blunted exercise response observed for cortisol, ACTH, and GH. Peripheral leukocytes and neutrophils were significantly increased in response to exercise in both the untreated and ICS-treated conditions, and at baseline after ICS-treatment. IL-6 was elevated with ICS-treatment but the exercise response blunted. Circulating mean fluticasone levels were 0.15 ng/mL and increased to 0.22 ng/mL in response to exercise.CONCLUSIONS: Exercise revealed deficits of the HPA axis and GH production after ICS-treatment not identified by static markers. Neutrophils were shown to be sensitive surrogate markers of the systemic effect of ICS. Exercise significantly increased circulating levels of fluticasone. Exercise challenge tests can be used to assess subtle, physiological impacts of exogenous corticosteroids. RATIONALE: Inhaled corticosteroids (ICS) improve lung disorders, such as asthma, by altering the immune system. Initial data suggest ICS effects remain localized to the lung; however, recent studies demonstrate alteration to the peripheral immune system in patients with asthma. We evaluated the effect of ICS on peripheral immune mediators and HPA axis, and their response to exercise, in healthy adult males. METHODS: Eleven healthy males (age 18-30 years old) were placed on 2 weeks of Fluticasone proprionate (440 mcg) twice daily. A 30 minute bout of exercise was performed on a cycle ergometer at about 70% peak work rate before and after the start of ICS. Blood was sampled pre- and end-exercise. Cytokines and HPA axis mediators were measured by ELISA and fluticasone by liquid chromatography/tandem mass spectrometry. RESULTS: After ICS-treatment, cortisol and ACTH were decreased and a blunted exercise response observed for cortisol, ACTH, and GH. Peripheral leukocytes and neutrophils were significantly increased in response to exercise in both the untreated and ICS-treated conditions, and at baseline after ICS-treatment. IL-6 was elevated with ICS-treatment but the exercise response blunted. Circulating mean fluticasone levels were 0.15 ng/mL and increased to 0.22 ng/mL in response to exercise. CONCLUSIONS: Exercise revealed deficits of the HPA axis and GH production after ICS-treatment not identified by static markers. Neutrophils were shown to be sensitive surrogate markers of the systemic effect of ICS. Exercise significantly increased circulating levels of fluticasone. Exercise challenge tests can be used to assess subtle, physiological impacts of exogenous corticosteroids.

Measuring behavioral perfomance in neurosensory experiments: the free tracking-framework (FTF)

Event Abstract Back to Event Measuring behavioral perfomance in neurosensory experiments: the free tracking-framework (FTF) Friedrich Kretschmer1*, Malte Ahlers2 and Jutta Kretzberg1 1 Carl-von-Ossietzky-Universität Oldenburg, Department of Computational Neuroscience, Germany 2 Carl-von-Ossietzky-Universität Oldenburg, Department of Neurobiology, Germany One of the main goals of neuroscience is to understand the neuronal basis of animal behavior. To approach this question experimentally, it is crucial to measure the animal's behavior with well-defined stimuli. By using the same stimuli for behavioral and neurophysiological experiments, neuronal responses can be related to behavioral performance. With this approach, it is possible to determine boundaries of the sensory system and to test hypotheses about the neural codes used in neurosensory information processing. For example, the combination of behavioral and neurophysiological experiments is very fruitful for the analysis of genetically modified animals, because it allows to characterize the function of the protein corresponding to the knocked out gene on a systemic level. For this purpose we have developed a universal single camera recording-system suitable for automated tracking of body, head and eye movements in small animals. Combined with a well-defined sensory stimulation, this system allows the reconstruction of the stimulus situation that was present at the receptor neurons during the experiment, providing the basis for neurophysiological experiments. The system tracks artificial and/or natural markers on the animal and estimates their 3D Position. For this purpose the framework combines several techniques from computer vision research, including contour-, region- and pattern-based tracking algorithms. 3D estimation is done by automatically measuring relative distances of at least four static markers attached to the animal in a series of different camera views. This allows the computation of distances to the camera center during an experiment on the basis of the perspective strain (Perspective-N-Point problem). The modular implementation of this software-framework enables the use of different tracking algorithms and the application in many different experimental environments. Tracking is done in on- or offline mode depending on the complexity of the applied algorithms. The free tracking-framework is currently being evaluated in a series of eye- and head-tracking experiments in mice and turtles while visually stimulating with user-defined moving 360° images through a panoramic mirror. At the conference, we will demonstrate the current version of the free tracking-framework. We will show how it is possible to automatically calibrate the camera and how different artificial markers attached to moving objects are tracked and their 3D positions are estimated. The resolution of a standard webcam provides a sufficient preciseness of the 3D estimation for many applications, and the source-code of this academic project will become available in an open source form in the future. Therefore, the free tracking-framework is designed to provide the basis for low-cost experimental setups to track animal behavior to complement studies in neurosensory science. Conference: Neuroinformatics 2010 , Kobe, Japan, 30 Aug - 1 Sep, 2010. Presentation Type: Oral Presentation Topic: General neuroinformatics Citation: Kretschmer F, Ahlers M and Kretzberg J (2010). Measuring behavioral perfomance in neurosensory experiments: the free tracking-framework (FTF). Front. Neurosci. Conference Abstract: Neuroinformatics 2010 . doi: 10.3389/conf.fnins.2010.13.00078 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 14 Jun 2010; Published Online: 14 Jun 2010. * Correspondence: Friedrich Kretschmer, Carl-von-Ossietzky-Universität Oldenburg, Department of Computational Neuroscience, Oldenburg, Germany, friedrich.kretschmer@informatik.uni-oldenburg.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Friedrich Kretschmer Malte Ahlers Jutta Kretzberg Google Friedrich Kretschmer Malte Ahlers Jutta Kretzberg Google Scholar Friedrich Kretschmer Malte Ahlers Jutta Kretzberg PubMed Friedrich Kretschmer Malte Ahlers Jutta Kretzberg Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Non-invasive stroke volume measurement and passive leg raising predict volume responsiveness in medical ICU patients: an observational cohort study

IntroductionThe assessment of volume responsiveness and the decision to administer a fluid bolus is a common dilemma facing physicians caring for critically ill patients. Static markers of cardiac preload are poor predictors of volume responsiveness, and dynamic markers are often limited by the presence of spontaneous respirations or cardiac arrhythmias. Passive leg raising (PLR) represents an endogenous volume challenge that can be used to predict fluid responsiveness.MethodsMedical intensive care unit (ICU) patients requiring volume expansion were eligible for enrollment. Non-invasive measurements of stroke volume (SV) were obtained before and during PLR using a transthoracic Doppler ultrasound device prior to volume expansion. Measurements were then repeated following volume challenge to classify patients as either volume responders or non-responders based on their hemodynamic response to volume expansion. The change in SV from baseline during PLR was then compared with the change in SV with volume expansion to determine the ability of PLR in conjunction with SV measurement to predict volume responsiveness.ResultsA total of 102 fluid challenges in 89 patients were evaluated. In 47 of the 102 fluid challenges (46.1%), SV increased by ≥15% after volume infusion (responders). A SV increase induced by PLR of ≥15% predicted volume responsiveness with a sensitivity of 81%, specificity of 93%, positive predictive value of 91% and negative predictive value of 85%.ConclusionsNon-invasive SV measurement and PLR can predict fluid responsiveness in a broad population of medical ICU patients. Less than 50% of ICU patients given fluid boluses were volume responsive.

Osteoclast Inhibitory Lectin, an Immune Cell Product That Is Required for Normal Bone Physiology in Vivo

Osteoclast inhibitory lectin (OCIL or clrb) is a member of the natural killer cell C-type lectins that have a described role mostly in autoimmune cell function. OCIL was originally identified as an osteoblast-derived inhibitor of osteoclast formation in vitro. To determine the physiological function(s) of OCIL, we generated ocil(-/-) mice. These mice appeared healthy and were fertile, with no apparent immune function defect, and phenotypic abnormalities were limited to bone. Histomorphometric analysis revealed a significantly lower tibial trabecular bone volume and trabecular number in the 10- and 16-week-old male ocil(-/-) mice compared with wild type mice. Furthermore, ocil(-/-) mice showed reduced bone formation rate in the 10-week-old females and 16-week-old males while Static markers of bone formation showed no significant changes in male or female ocil(-/-) mice. Examination of bone resorption markers in the long bones of ocil(-/-) mice indicated a transient increase in osteoclast number per unit bone perimeter. Enhanced osteoclast formation was also observed when either bone marrow or splenic cultures were generated in vitro from ocil(-/-) mice relative to wild type control cultures. Loss of ocil therefore resulted in osteopenia in adult mice primarily as a result of increased osteoclast formation and/or decreased bone formation. The enhanced osteoclastic activity led to elevated serum calcium levels, which resulted in the suppression of circulating parathyroid hormone in 10-week-old ocil(-/-) mice compared with wild type control mice. Collectively, our data suggest that OCIL is a physiological negative regulator of bone.

Bone mineral density in the proximal tibia varies as a function of static alignment and knee adduction angular momentum in individuals with medial knee osteoarthritis

Based on the premise that bone mass and bone geometry are related to load history and that subchondral bone may play a role in osteoarthritis (OA), we sought to determine if static and dynamic markers of knee joint loads explain variance in the medial-to-lateral ratio of proximal tibial bone mineral density (BMD) in subjects with mild and moderate medial knee OA. We utilized two surrogate markers of dynamic load, the peak knee adduction moment and the knee adduction angular momentum, the latter being the time integral of the frontal plane knee joint moment. BMD for medial and lateral regions of the proximal tibial plateau and one distal region in the tibial shaft was measured in 84 symptomatic subjects with Kellgren and Lawrence radiographic OA grades of 2 or 3. Utilizing gait analysis, the peak knee adduction moment (the external adduction moment of greatest magnitude) and the time integral of the frontal plane knee joint moment (the angular momentum) over the entire stance phase as well as for each of the four subdivisions of stance were calculated. The BMD ratio was not significantly different in grade 2 (1.32 ± 0.27) and grade 3 knees (1.47 ± 0.40) (P = 0.215). BMD of the tibial shaft was not correlated with any loading parameter or static alignment. Of all the surrogate gait markers of dynamic load, the knee adduction angular momentum in terminal stance explained the most variance (20%) in the medial-to-lateral BMD ratio (adjusted r2 = 0.196, P < 0.001). The knee adduction angular momentum for the entire stance phase explained 18% of the variance in the BMD ratio (adjusted r2 = 0.178, P < 0.001), 10% more variance than explained by the overall peak knee adduction moment (adjusted r2 = 0.081, P < 0.001). 18% of the variance in the BMD ratio was also explained by the knee alignment angle (adjusted r2 = 0.183, P < 0.001), and the total explanatory power was increased to 22% when the knee adduction angular momentum in terminal stance was added (change in r2 = 0.041, P < 0.05, total adjusted r2 = 0.215, P < 0.001). The BMD ratio and its relationship to dynamic and static markers of loading were independent of height, weight, and the body mass index, demonstrating that both dynamic markers of knee loading as well as knee alignment explained variance in the tibial BMD ratio independent of body size.

Invasive measures of left ventricular preload

Cardiac preload is frequently altered during hemodynamic failure and is a major focus of therapeutic management. The aim of this review was to summarize the invasive indicators of preload and the invasive predictors of preload responsiveness. The static assessment of preload is based on the measurement of pulmonary artery occlusion pressure, which is still considered a gold standard. The reliability of the transpulmonary dilution method for bedside monitoring of cardiac volumes and preload has been clearly documented. Nonetheless, a number of recent studies have emphasized the poor value of static markers of preload for predicting a positive response to fluid therapy in comparison to 'dynamic' or 'functional' indices. Among them, the respiratory variation of arterial pulse pressure has been confirmed by numerous studies as an excellent indicator of volume responsiveness. The limitations for using these dynamic parameters have recently been emphasized so that alternative methods, such as passive leg raising or the respiratory systolic variation test, have been developed. The best prediction of the hemodynamic response to fluid therapy is afforded by functional evaluation of preload responsiveness rather than by static markers of preload.

Does pravastatin increase chylomicron remnant catabolism in postmenopausal women with type 2 diabetes mellitus?

We investigated the effects of pravastatin on chylomicron remnant catabolism measured with a 13C stable isotope breath test and plasma apolipoprotein (apo) B-48 and remnant-like particle (RLP)-cholesterol in postmenopausal women with type 2 diabetes mellitus. Nineteen postmenopausal women with type 2 diabetes were randomized to receive 40 mg/day pravastatin or no treatment for 6 weeks followed by a 2-week washout period, and crossed over for a further 6 weeks. Fractional catabolic rate (FCR) of a chylomicron remnant-like emulsion was determined from 13CO2 enrichment in the breath and plasma using isotope-ratio mass spectrometry and multicompartmental modelling. Plasma apo B-48 and RLP-cholesterol concentrations were also measured as static markers of chylomicron remnant metabolism. Pravastatin significantly reduced plasma concentrations of cholesterol (5.9 +/- 0.3 vs. 4.8 +/- 0.2 mmol/l; P < 0.001), low density lipoprotein (LDL)-cholesterol (3.5 +/- 0.2 vs. 2.6 +/- 0.2 mmol/l; P < 0.001), triglyceride (2.1 +/- 0.3 vs. 1.7 +/- 0.2 mmol/l; P = 0.017), non-high density lipoprotein (HDL)-cholesterol (4.4 +/- 0.3 vs. 3.3 +/- 0.2 mmol/l; P < 0.001), lathosterol/total cholesterol ratio (2.6 +/- 0.2 vs. 2.0 +/- 0.3, P = 0.035), apo B-100 (1.1 +/- 0.1 vs. 0.8 +/- 0.1 g/l; P = 0.001), apo B-48 (4.8 +/- 0.9 vs. 3.3 +/- 0.6 mg/l; P = 0.016), and RLP-cholesterol (31.4 +/- 8.2 vs. 18.6 +/- 4.6 mg/dl; P = 0.024). Pravastatin was also associated with an increase in sitosterol/total cholesterol ratio (2.8 +/- 0.3 vs. 3.1 +/- 0.3, P = 0.029). Chylomicron remnant-like emulsion catabolism was not, however, significantly altered by pravastatin estimated by either breath or plasma clearance measurements. In postmenopausal women, pravastatin decreases plasma concentrations of remnant lipoproteins by a mechanism that may relate chiefly to inhibition of remnant production, but this requires further evaluation.

Simultaneous Measurement of Three-Dimensional Joint Kinematics and Ligament Strains With Optical Methods

The objective of this study was to assess the precision and accuracy of a nonproprietary, optical three-dimensional (3D) motion analysis system for the simultaneous measurement of soft tissue strains and joint kinematics. The system consisted of two high-resolution digital cameras and software for calculating the 3D coordinates of contrast markers. System precision was assessed by examining the variation in the coordinates of static markers over time. Three-dimensional strain measurement accuracy was assessed by moving contrast markers fixed distances in the field of view and calculating the error in predicted strain. Three-dimensional accuracy for kinematic measurements was assessed by simulating the measurements that are required for recording knee kinematics. The field of view (190 mm) was chosen to allow simultaneous recording of markers for soft tissue strain measurement and knee joint kinematics. Average system precision was between +/-0.004 mm and +/-0.035 mm, depending on marker size and camera angle. Absolute error in strain measurement varied from a minimum of +/-0.025% to a maximum of +/-0.142%, depending on the angle between cameras and the direction of strain with respect to the camera axes. Kinematic accuracy for translations was between +/-0.008 mm and +/-0.034 mm, while rotational accuracy was +/-0.082 deg to +/-0.160 deg. These results demonstrate that simultaneous optical measurement of 3D soft tissue strain and 3D joint kinematics can be performed while achieving excellent accuracy for both sets of measurements.

Respiratory variations of aortic VTI: a new index of hypovolemia and fluid responsiveness.

In 12 mechanically ventilated and anesthetized rabbits, we investigated whether the magnitude of respiratory changes in the aortic velocity time integral (VTI(Ao)), recorded by transthoracic echocardiography (TTE) during a stepwise blood withdrawal and restitution, could be used as a reliable indicator of volume depletion and responsiveness. At each step, left and right ventricular dimensions and the aortic diameter and VTI(Ao) were recorded to calculate stroke volume (SV) and cardiac output (CO). Respiratory changes of VTI(Ao) (maximal - minimal values divided by their respective means) were calculated. The amount of blood withdrawal correlated negatively with left and right ventricular diastolic diameters, VTI(Ao), SV, and CO and correlated directly with respiratory changes of VTI(Ao). Respiratory VTI(Ao) variations (but not other parameters) at the last blood withdrawal step was also correlated with changes in SV after blood restitution (r = 0.83, P < 0.001). In conclusion, respiratory variations in VTI(Ao) using TTE appear to be a sensitive index of blood volume depletion and restitution. This dynamic parameter predicted fluid responsiveness more reliably than static markers of cardiac preload.

Functional alterations in CNS catecholamine systems in adolescence and adulthood after neonatal chlorpyrifos exposure

Chlorpyrifos (CPF), one of the most widely used pesticides, is a neurobehavioral teratogen in animals. We administered CPF to neonatal rats on postnatal days (PN) 1–4 (1 mg/kg) or PN11–14 (5 mg/kg), regimens devoid of overt systemic toxicity. We then examined the impact on catecholaminergic systems in adolescence (PN30) and adulthood (PN60), assessing basal neurotransmitter content and transmitter utilization rates (turnover) in brain regions comprising the major noradrenergic and dopaminergic projections. Although CPF had only sporadic effects on basal norepinephrine and dopamine content, it profoundly suppressed norepinephrine turnover across multiple regions, indicative of net reductions in presynaptic activity. Dopamine turnover showed less consistent effects, with subnormal turnover in some regions and activation in others. We also evaluated whether CPF exposure altered the ability of catecholamine systems to respond to acute cholinergic stimulation, elicited by administration of a single challenge dose of nicotine. In the normal brain, nicotine increases the utilization of norepinephrine and dopamine. With only a few exceptions, animals receiving neonatal CPF exposure showed lasting desensitization of the nicotine response; not only was the activation by nicotine blunted in the CPF group, but in some regions the nicotine response was reversed, eliciting a reduction in transmitter turnover. These results indicate that neonatal CPF exposure produces widespread deficiencies in catecholaminergic synaptic function that persist into adulthood, and that are best revealed by dynamic measures of synaptic activity and responsiveness, as opposed to static markers like basal transmitter levels. The effects seen here are likely to contribute to alterations in behavioral performance that persist or emerge long after the termination of CPF exposure.