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At least 1,027 records · Page 57

Application of multivariate statistics to vestibular testing: discriminating between Meniere's disease and migraine associated dizziness

Meniere's disease (MD) and migraine associated dizziness (MAD) are two disorders that can have similar symptomatologies, but differ vastly in treatment. Vestibular testing is sometimes used to help differentiate between these disorders, but the inefficiency of a human interpreter analyzing a multitude of variables independently decreases its utility. Our hypothesis was that we could objectively discriminate between patients with MD and those with MAD using select variables from the vestibular test battery. Sinusoidal harmonic acceleration test variables were reduced to three vestibulo-ocular reflex physiologic parameters: gain, time constant, and asymmetry. A combination of these parameters plus a measurement of reduced vestibular response from caloric testing allowed us to achieve a joint classification rate of 91%, independent quadratic classification algorithm. Data from posturography were not useful for this type of differentiation. Overall, our classification function can be used as an unbiased assistant to discriminate between MD and MAD and gave us insight into the pathophysiologic differences between the two disorders.

NASA Discipline Neuroscience↗

Signal averaging technique for noninvasive recording of late potentials in patients with coronary artery disease

An advanced non invasive signal averaging technique was used to detect late potentials in two groups of patients: Group A (24 patients) with coronary artery disease (CAD) and without sustained ventricular tachycardia (VT) and Group B (8 patients) with CAD and sustained VT. Recorded analog data were digitized and aligned using a cross correlation function with fast Fourier transform schema, averaged and band pass filtered between 60 and 200 Hz with a non-recursive digital filter. Averaged filtered waveforms were analyzed by computer program for 3 parameters: (1) filtered QRS (fQRS) duration (2) interval between the peak of the R wave peak and the end of fQRS (R-LP) (3) RMS value of last 40 msec of fQRS (RMS). Significant change was found between Groups A and B in fQRS (101 -/+ 13 msec vs 123 -/+ 15 msec; p < .0005) and in R-LP vs 52 -/+ 11 msec vs 71-/+18 msec, p <.002). We conclude that (1) the use of a cross correlation triggering method and non-recursive digital filter enables a reliable recording of late potentials from the body surface; (2) fQRS and R-LP durations are sensitive indicators of CAD patients susceptible to VT.

NASA Discipline Cardiopulmonary↗

Crystallization and preliminary X-ray analysis of recombinant human acid beta-glucocerebrosidase, a treatment for Gaucher's disease

Acid beta-glucocerebrosidase (N-acylsphingosyl-1-O-beta-D-glucoside:glucohydrolase) is a lysosomal glycoprotein that catalyzes the hydrolysis of the glycolipid glucocerebroside to glucose and ceramide. Inadequate levels of this enzyme underly the pathophysiology of Gaucher's disease. Cerezyme (Genzyme Corporation, Cambridge, MA, USA) is a partially deglycosylated form of recombinant human acid beta-glucocerebrosidase that is used in the treatment of Gaucher patients. Although acid beta-glucocerebrosidase belongs to a large family of glycosidases, relatively little is known regarding its structural biology. Here, the crystallization and the initial diffraction analysis of Cerezyme are reported. The crystals are C-centered orthorhombic, with unit-cell parameters a = 285.0, b = 110.2, c = 91.7 A. A 99.9% complete data set has been collected to 2.75 A with an R(sym) of 8.8%.

Glucosylceramidase/chemistry↗

Ceruloplasmin and cardiovascular disease

Transition metal ion-mediated oxidation is a commonly used model system for studies of the chemical, structural, and functional modifications of low-density lipoprotein (LDL). The physiological relevance of studies using free metal ions is unclear and has led to an exploration of free metal ion-independent mechanisms of oxidation. We and others have investigated the role of human ceruloplasmin (Cp) in oxidative processes because it the principal copper-containing protein in serum. There is an abundance of epidemiological data that suggests that serum Cp may be an important risk factor predicting myocardial infarction and cardiovascular disease. Biochemical studies have shown that Cp is a potent catalyst of LDL oxidation in vitro. The pro-oxidant activity of Cp requires an intact structure, and a single copper atom at the surface of the protein, near His(426), is required for LDL oxidation. Under conditions where inhibitory protein (such as albumin) is present, LDL oxidation by Cp is optimal in the presence of superoxide, which reduces the surface copper atom of Cp. Cultured vascular endothelial and smooth muscle cells also oxidize LDL in the presence of Cp. Superoxide release by these cells is a critical factor regulating the rate of oxidation. Cultured monocytic cells, when activated by zymosan, can oxidize LDL, but these cells are unique in their secretion of Cp. Inhibitor studies using Cp-specific antibodies and antisense oligonucleotides show that Cp is a major contributor to LDL oxidation by these cells. The role of Cp in lipoprotein oxidation and atherosclerotic lesion progression in vivo has not been directly assessed and is an important area for future studies.

NASA Discipline Cell Biology↗

Transesophageal echocardiography: first-line imaging for aortic diseases

Transesophageal echocardiography (TEE) is now commonly used to evaluate the thoracic aorta, because it is widely available and provides high-resolution images and flow information by Doppler. This article reviews the essential features on TEE of acute and chronic aortic diseases, such as aortic dissection, aneurysm, and atherosclerosis, and discusses its strengths, weaknesses, and indications.

NASA Program Biomedical Research and Countermeasur↗

Stress failure of pulmonary capillaries: role in lung and heart disease

Pulmonary capillaries have extremely thin walls to allow rapid exchange of respiratory gases across them. Recently it has been shown that the wall stresses become very large when the capillary pressure is raised, and in anaesthetised rabbits, ultrastructural damage to the walls is seen at pressures of 40 mm Hg and above. The changes include breaks in the capillary endothelial layer, alveolar epithelial layer, and sometimes all layers of the wall. The strength of the thin part of the capillary wall can be attributed to the type IV collagen in the extracellular matrix. Stress failure of pulmonary capillaries results in a high-permeability form of oedema, or even frank haemorrhage, and is apparently the mechanism of neurogenic pulmonary oedema and high-altitude pulmonary oedema. It also explains the exercise-induced pulmonary haemorrhage that occurs in all racehorses. Several features of mitral stenosis are consistent with stress failure. Overinflation of the lung also leads to stress failure, a common cause of increased capillary permeability in the intensive care environment. Stress failure also occurs if the type IV collagen of the capillary wall is weakened by autoantibodies as in Goodpasture's syndrome. Neutrophil elastase degrades type IV collagen and this may be the starting point of the breakdown of alveolar walls that is characteristic of emphysema. Stress failure of pulmonary capillaries is a hitherto overlooked and potentially important factor in lung and heart disease.

Review↗

Production and characterization of monoclonal antibodies to budgerigar fledgling disease virus major capsid protein VP

Eleven hybridoma cell lines producing monoclonal antibodies (MAbs) against intact budgerigar fledgling disease (BFD) virions were produced and characterized. These antibodies were selected for their ability to react with BFD virions in an enzyme-linked immunosorbent assay. Each of these antibodies was reactive in the immunofluorescent detection of BFD virus-infected cells. These antibodies immunoprecipitated intact virions and specifically recognized the major capsid protein, VP1, of the dissociated virion. The MAbs were found to preferentially recognize native BFD virus capsid protein when compared with denatured virus protein. These MAbs were capable of detecting BFD virus protein in chicken embryonated cell-culture lysates by dot-blot analysis.

Non-NASA Center↗

Phosphorylation of the budgerigar fledgling disease virus major capsid protein VP1

The structural proteins of the budgerigar fledgling disease virus, the first known nonmammalian polyomavirus, were analyzed by isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The major capsid protein VP1 was found to be composed of at least five distinct species having isoelectric points ranging from pH 6.45 to 5.85. By analogy with the murine polyomavirus, these species apparently result from different modifications of an initial translation product. Primary chicken embryo cells were infected in the presence of 32Pi to determine whether the virus structural proteins were modified by phosphorylation. SDS-PAGE of the purified virus structural proteins demonstrated that VP1 (along with both minor capsid proteins) was phosphorylated. Two-dimensional analysis of the radiolabeled virus showed phosphorylation of only the two most acidic isoelectric species of VP1, indicating that this posttranslational modification contributes to VP1 species heterogeneity. Phosphoamino acid analysis of 32P-labeled VP1 revealed that phosphoserine is the only phosphoamino acid present in the VP1 protein.

Non-NASA Center↗

Coronary Artery Disease Alters Ventricular Repolarization Dynamics in Type 2 Diabetes

Ventricular repolarization dynamics (VRD) is an important predictor of outcome in diabetes. We examined the potential impact of coronary artery disease (CAD) on VRD in type 2 diabetic patients. We recorded 5-min high-resolution resting electrocardiograms (ECG) in 38 diabetic patients undergoing elective coronary angiography, and in 38 age- and gender- matched apparently healthy subjects (Controls). Using leads I and II, time-domain indices of VRD were calculated. Coronary angiography was regarded as positive if a 350% stenosis was found. Angiography was positive in 21 diabetic patients (55%). Patients with CAD had a significantly higher degree of VRD than Controls (SDNN(QT): 15.81+/-7.22 ms vs. 8.94+/-6.04 ms; P <0.001, rMSSD(QT): 21.02k7.07 ms vs. 11.18k7.45 ms; P <0.001). VRD in diabetic patients with negative angiograms did not differ from VRD in Controls (SDNN(QT): 8.94+/-6.04 ms vs. 7.44+/-5.72 ms; P=0.67, rMSSD(QT): 11.18+/-7.45 ms vs. 10.22+/-5.35 ms; P=O. 82). CAD increases VRD in patients with type 2 diabetes. Therefore, changes in ventricular repolarization in diabetic patients may be due to silent CAD rather than to diabetes per se.

Vrtovec, Bojan↗

Studying Host-Pathogen Interactions In 3-D: Organotypic Models For Infectious Disease And Drug Development

Representative, reproducible and high-throughput models of human cells and tissues are critical for a meaningful evaluation of host-pathogen interactions and are an essential component of the research developmental pipeline. The most informative infection models - animals, organ explants and human trials - are not suited for extensive evaluation of pathogenesis mechanisms and screening of candidate drugs. At the other extreme, more cost effective and accessible infection models such as conventional cell culture and static co-culture may not capture physiological and three-dimensional aspects of tissue biology that are important in assessing pathogenesis, and effectiveness and cytotoxicity of therapeutics. Our lab has used innovative bioengineering technology to establish biologically meaningful 3-D models of human tissues that recapitulate many aspects of the differentiated structure and function of the parental tissue in vivo, and we have applied these models to study infectious disease. We have established a variety of different 3-D models that are currently being used in infection studies - including small intestine, colon, lung, placenta, bladder, periodontal ligament, and neuronal models. Published work from our lab has shown that our 3-D models respond to infection with bacterial and viral pathogens in ways that reflect the infection process in vivo. By virtue of their physiological relevance, 3-D cell cultures may also hold significant potential as models to provide insight into the neuropathogenesis of HIV infection. Furthermore, the experimental flexibility, reproducibility, cost-efficiency, and high throughput platform afforded by these 3-D models may have important implications for the design and development of drugs with which to effectively treat neurological complications of HIV infection.

Nickerson, Cheryl A.↗

Construction of a Resting High Fidelity ECG "SuperScore" for Management and Screening of Heart Disease

Resting conventional ECG is notoriously insensitive for detecting coronary artery disease (CAD) and only nominally useful in screening for cardiomyopathy (CM). Similarly, conventional exercise stress test ECG is both time- and labor-consuming and its accuracy in identifying CAD is suboptimal for use in population screening. We retrospectively investigated the accuracy of several advanced resting electrocardiographic (ECG) parameters, both alone and in combination, for detecting CAD and cardiomyopathy (CM).

Schlegel, Todd T.↗

Multi-channel System for Beat to Beat QT Interval Variability and its Use in Screening for Coronary Artery Disease and Cardiomyopathy

We investigated the ability of beat-to-beat QT interval variability (QTV) and related parameters to differentiate healthy individuals from patients with obstructive coronary artery disease (CAD) and cardiomyopathy (CM). For this purpose we developed a PC-based ECG software program that in real time, acquires, analyzes and displays QTV in each of the eight independent channels that constitute the 12-lead conventional ECG. The system also analyzes and displays the QTV from QT interval signals that are derived from multiple channels and from singular value decomposition (SVD) to substantially reduce the effect of noise and other artifacts on the QTV results. It also provides other useful SVD-related parameters such as the normalized 3-dimensional volume of the T wave (nTV) = 100*(rho(sub 2)*rho(sub 3)rho(sub 1^2). Advanced high-fidelity 12-lead ECG tests (approx. 5-min supine) were first performed on a "training set" of 99 individuals: 33 with ischemic or dilated CM and low ejection fraction (EF less than 40%); 33 with catheterization-proven obstructive CAD but normal EF; and 33 age-/gender-matched healthy controls. All QTV parameters that were studied for their accuracy in detecting CM and CAD significantly differentiated both CM and CAD from controls (p less than 0.0001). Retrospective areas under the ROC curve (AUC) of SDNN-QTV, rmsSD-QTV, and QTV Index (QTVI) for CM vs. controls in the lead V5 were 0.85, 0.90, and 0.99, respectively, and those for CAD vs. controls in the lead II were 0.82, 0.82, and 0.89. Other advanced ECG parameters, such as HFQRS RAZ score, LF Lomb of RRV or QRS-T angle, differentiated both CM and CAD from controls less significantly, with the respective AUC values of 0.89, 0.88 and 0.98 for CM vs. controls, and 0.73, 0.71 and 0.80 for CAD vs. controls. QTV parameters (especially QTVI, which is QTV as indexed to RRV) were, diagnostically speaking, amongst the best performing of the advanced ECG techniques studied thus far.

Starc, V.↗

Noninvasive Test Detects Cardiovascular Disease

At NASA's Jet Propulsion Laboratory (JPL), NASA-developed Video Imaging Communication and Retrieval (VICAR) software laid the groundwork for analyzing images of all kinds. A project seeking to use imaging technology for health care diagnosis began when the imaging team considered using the VICAR software to analyze X-ray images of soft tissue. With marginal success using X-rays, the team applied the same methodology to ultrasound imagery, which was already digitally formatted. The new approach proved successful for assessing amounts of plaque build-up and arterial wall thickness, direct predictors of heart disease, and the result was a noninvasive diagnostic system with the ability to accurately predict heart health. Medical Technologies International Inc. (MTI) further developed and then submitted the technology to a vigorous review process at the FDA, which cleared the software for public use. The software, patented under the name Prowin, is being used in MTI's patented ArterioVision, a carotid intima-media thickness (CIMT) test that uses ultrasound image-capturing and analysis software to noninvasively identify the risk for the major cause of heart attack and strokes: atherosclerosis. ArterioVision provides a direct measurement of atherosclerosis by safely and painlessly measuring the thickness of the first two layers of the carotid artery wall using an ultrasound procedure and advanced image-analysis software. The technology is now in use in all 50 states and in many countries throughout the world.

Source record↗

Predicting and Mitigating Outbreaks of Vector-Borne Disease Utilizing Satellite Remote Sensing Technology and Models

The Public Health application area focuses on Earth science applications to public health and safety, particularly regarding infectious disease, emergency preparedness and response, and environmental health issues. The application explores issues of toxic and pathogenic exposure, as well as natural and man-made hazards and their effects, for risk characterization/mitigation and improvements to health and safety. The program elements of the NASA Applied Sciences Program are: Agricultural Efficiency, Air Quality, Climate, Disaster Management, Ecological Forecasting, Water Resources, Weather, and Public Health.

Estes, Sue M.↗

Noninvasive Diagnosis of Coronary Artery Disease Using 12-Lead High-Frequency Electrocardiograms

A noninvasive, sensitive method of diagnosing certain pathological conditions of the human heart involves computational processing of digitized electrocardiographic (ECG) signals acquired from a patient at all 12 conventional ECG electrode positions. In the processing, attention is focused on low-amplitude, high-frequency components of those portions of the ECG signals known in the art as QRS complexes. The unique contribution of this method lies in the utilization of signal features and combinations of signal features from various combinations of electrode positions, not reported previously, that have been found to be helpful in diagnosing coronary artery disease and such related pathological conditions as myocardial ischemia, myocardial infarction, and congestive heart failure. The electronic hardware and software used to acquire the QRS complexes and perform some preliminary analyses of their high-frequency components were summarized in Real-Time, High-Frequency QRS Electrocardiograph (MSC- 23154), NASA Tech Briefs, Vol. 27, No. 7 (July 2003), pp. 26-28. To recapitulate, signals from standard electrocardiograph electrodes are preamplified, then digitized at a sampling rate of 1,000 Hz, then analyzed by the software that detects R waves and QRS complexes and analyzes them from several perspectives. The software includes provisions for averaging signals over multiple beats and for special-purpose nonrecursive digital filters with specific low- and high-frequency cutoffs. These filters, applied to the averaged signal, effect a band-pass operation in the frequency range from 150 to 250 Hz. The output of the bandpass filter is the desired high-frequency QRS signal. Further processing is then performed in real time to obtain the beat-to-beat root mean square (RMS) voltage amplitude of the filtered signal, certain variations of the RMS voltage, and such standard measures as the heart rate and R-R interval at any given time. A key signal feature analyzed in the present method is the presence versus the absence of reduced-amplitude zones (RAZs). In terms that must be simplified for the sake of brevity, an RAZ comprises several cycles of a high-frequency QRS signal during which the amplitude of the high-frequency oscillation in a portion of the signal is abnormally low (see figure). A given signal sample exhibiting an interval of reduced amplitude may or may not be classified as an RAZ, depending on quantitative criteria regarding peaks and troughs within the reduced-amplitude portion of the high-frequency QRS signal. This analysis is performed in all 12 leads in real time.

Schlegel, Todd T.↗

Toxicity of Mineral Dusts and a Proposed Mechanism for the Pathogenesis of Particle-Induced Lung Diseases

Humans will set foot on the moon again. The lunar surface has been bombarded for 4 billion years by micrometeoroids and cosmic radiation, creating a layer of fine dust having a potentially reactive particle surface. To investigate the impact of surface reactivity (SR) on the toxicity of particles, and in particular, lunar dust (LD), we ground 2 Apollo 14 LD samples to increase their SR and compare their toxicity with those of unground LD, TiO2 and quartz. Intratracheally instilled at 0, 1, 2.5, or 7.5 mg/rat, all dusts caused dose-dependent increases in pulmonary lesions, and enhancement of biomarkers of toxicity assessed in bronchoalveolar lavage fluids (BALF). The toxicity of LD was greater than that of TiO2 but less than that of quartz. Three LDs differed 14-fold in SR but were equally toxic; quartz had the lowest SR but was most toxic. These results show no correlation between particle SR and toxicity. Often pulmonary toxicity of a dust can be attributed to oxidative stress (OS). We further observed dose-dependent and dustcytotoxicity- dependent increases in neutrophils. The oxidative content per BALF cell was also directly proportional to both the dose and cytotoxicity of the dusts. Because neutrophils are short-lived and release of oxidative contents after they die could initiate and promote a spectrum of lesions, we postulate a general mechanism for the pathogenesis of particle-induced diseases in the lung that involves chiefly neutrophils, the source of persistent endogenous OS. This mechanism explains why one dust (e.g., quartz or nanoparticles) is more toxic than another (e.g., micrometer-sized TiO2), why dust-induced lesions progress with time, and why lung cancer occurs in rats but not in mice and hamsters exposed to the same duration and concentration of dust.

Lam, C.‐W.↗

NASA Screening and Clinical Practice for the Monitoring and Mitigation of Coronary Artery Disease: Application to Terrestrial Practice

Coronary artery disease (CAD) surveillance has led to the development of risk stratification tools that drive clinical mitigation efforts for CAD risk. As common risk assessment tools, including the Framingham Risk Score (FRS) or Pooled Cohort Risk Equations, have insufficient accuracy on an individual level to meet NASA’s stringent screening guidelines, NASA has required new approaches to address the risk of catastrophic cardiovascular (CV) medical events among astronauts. Coronary artery calcium (CAC) scanning has emerged as the current best tool to enhance CV risk assessment in asymptomatic individuals, with risk information incremental to FRS data.

Khera, Amit↗

Terrestrial Cardiovascular Coronary Artery Disease (CAD) Screening, Treatment and Risk Mitigation - Lessons Learned from Space Medicine

The Bellagio II Summit sought to correlate current ISS (International Space Station) Space Medicine practice in the screening/assessment and management of CAD (Coronary Artery Disease) and to identify terrestrial applications for the general population pertaining to primary, secondary and tertiary diagnoses and treatments. We identified current Space Medicine practice for screening and monitoring cosmonaut and astronaut in the pre-, in-, and post-flight mission phases. We will discuss current Space Medicine standards and guidelines in the recognition and monitoring of CAD development, stabilization, and regression.

Johnston, Smith↗