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Nonpulsatile and noninvasive transmittance and reflectance tissue-bed oximetry.

A new optical device was developed that measures blood pressure noninvasively, in small human subjects (neonates and premature infants) and small animals (Roeder RAR. Transducer for indirect measurement of blood pressure in small human subjects and animals, Purdue University, BME; 2003.: xi, 50 p.). The ability of this device to measure oxygen saturation enhances its value. The objective of this research was to add the ability to obtain SaO(2) from the same device and to obtain the calibration curve. Another objective was to determine which measurement method (transmittance or reflectance) is preferable. This new oximeter is unlike the conventional pulse oximeter in that it does not require a pulse, making it ideal for measuring oxygen saturation noninvasively in small human subjects with small amplitude pulses or without a pulse. A study was performed in 11 pigs, ranging in weight 20-27 kg. The pig tail was used as the measuring site for %SaO(2) measurements. Arterial blood samples were obtained from the femoral artery and oxygen saturation was measured with a blood-gas analyzer. A small blood-pressure cuff was used to render the optical path bloodless. A comparison of the transmittance and reflectance methods for measuring oxygen saturation was made. %SaO(2) measurements ranged from 4% to 100%. It was found that both the transmittance and reflectance methods can be used to measure %SaO(2) reliably in situations with or without a pulse.

Algorithms↗

Low vision rehabilitation in patients with age-related macular degeneration at a tertiary eye care centre in southern India.

PURPOSE: To evaluate the specific needs and types of low vision devices (LVDs) in patients with age-related macular degeneration (AMD) so as to use the residual vision effectively. METHODS: One hundred consecutive patients with diagnosis of AMD were evaluated to ascertain the degree of visual disability. Different LVDs were used to suit the specific needs of individual patients. The distribution of LVDs for distance and near and other rehabilitation measures were stratified for vision >or=6/18 and <6/18. Statistical analysis was performed using chi2 test/Fisher's exact test and paired t-test. RESULTS: The percentage of patients with visual acuity <6/18 reduced from 72.2% (26/36) to 47.2% (17/36) with the use of standard spectacles (P = 0.03). Similarly, the percentage of patients with visual acuity <6/18 reduced from 85.7% (6/7) to 14.3% (1/7) with the use of a telescope (P = 0.029). The optical devices for near tasks included spectacle magnifiers (n = 59), stand magnifiers (n = 19), and hand magnifiers (n = 18). With these LVDs, the near vision improved from 0.13 (decimal notations) to 0.39 (P < 0.001). Eighty-six patients were given at least one of the LVDs and 20% were prescribed more than one near device (bifocals, spectacle magnifiers, hand magnifiers, stand magnifiers). Additionally, patients also needed counselling (n = 89) and training on eccentric viewing (n = 39), coin identification (n = 45), and independent mobility (n = 41). CONCLUSION: The overall management of a patient with AMD must include counselling, prescription of appropriate LVDs and training to utilize the residual vision to its fullest advantage. This is expected to improve the patient's quality of life.

Aged↗

Two-step transcriptional amplification as a method for imaging reporter gene expression using weak promoters.

We are developing assays to image tissue-specific reporter gene expression in living mice by using optical methods and positron emission tomography. Approaches for imaging reporter gene expression depend on robust levels of mRNA and reporter protein. Attempts to image reporter gene expression driven by weak promoters are often hampered by the poor transcriptional activity of such promoters. Most tissue-specific promoters are weak relative to stronger but constitutively expressing viral promoters. In this study, we have validated methods to enhance the transcriptional activity of the prostate-specific antigen promoter for imaging by using a two-step transcriptional amplification (TSTA) system. We used the TSTA system to amplify expression of firefly luciferase (fl) and mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) in a prostate cancer cell line (LNCaP). We demonstrate approximately 50-fold (fl) and approximately 12-fold (HSV1-sr39tk) enhancement by using the two-step approach. The TSTA system is observed to retain tissue selectivity. A cooled charge-coupled device optical imaging system was used to visualize the amplified fl expression in living mice implanted with LNCaP cells transfected ex vivo. These imaging experiments reveal a approximately 5-fold gain in imaging signal by using the TSTA system over the one-step system. The TSTA approach will be a valuable and generalizable tool to amplify and noninvasively image reporter gene expression in living animals by using tissue-specific promoters. The approaches validated should have important implications for study of gene therapy vectors, cell trafficking, transgenic models, as well as studying development of eukaryotic organisms.

Animals↗

Transducers, sensors, and instrumentation in clinical biomechanics.

Successful measurements in any field are dependent on the availability of appropriate transducer materials and the associated instrumentation. In recent years there has been a most welcome advance in both these areas. If we consider first the transducer developments that have recently taken place, these have much to do with the discovery and application of new materials such as electroactive polymers, fibre optic devices and many others. Instrumentation has largely benefitted from the microelectronics revolution. Our ability to process and ultimately display data has improved to a remarkable extent. Indeed, the designer of instrumentation is under enormous pressure to convert the data into the digital domain as early as possible simply because the resulting instrument will usually be easier to design and construct, more accurate, more reliable, smaller and possibly more important still, cheaper. This paper reviews some of these developments, gives a number of examples of applications in the clinical biomechanics area and makes some predictions for future developments.

Biomechanical Phenomena↗

Photon undulatory non-linear conversion diagnostic method for caries detection: a pilot study.

OBJECTIVE: The objective of this study was to evaluate a new optical method - photon undulatory non-linear conversion (PNC)--for use in different stages of caries detection. BACKGROUND DATA: Caries should be considered an infectious disease managed by risk assessment, early detection, and preventive therapies, rather than simply "drilling and filling." MATERIAL AND METHODS: Fluorescence emission spectroscopy was performed in vitro on 90 extracted teeth, with intact occlusal surfaces. This system differs from the basic Diagnodent unit in its ability to distinguish between different tissue components with respect to their spectrums. Histological analysis served as the gold standard for verification. The teeth sections correspond to the specific point with the highest reading of the detector. The system was compared to visual inspection, probing, and x-ray methods. The system tested (helium-neon [He-Ne], lambda = 633 nm) has a fiber optic device that delivers radiation to the tooth and a spectrophotometer device that detects bacterial porphyrins fluorescence, allowing detection of caries, fillings, and calculus by simultaneous measurement of backscattering and fluorescence intensity. RESULTS: The system tested provides quantitatively reproducible measurements and detection even through sound enamel of more than 1 mm in thickness. CONCLUSION: The PNC method detects different stages of caries lesions in real time, and it exceeds x-rays in sensitivity, without any ionizing radiation. Preliminary results showed a high potential of using the PNC method in clinical practice (98% accuracy) in comparison to the other methods.

Dental Caries↗

Shadows cast by retinal blood vessels mapped in primary visual cortex.

The mammalian eye is a remarkable optical device, but its design is not perfect. The blood vessels that supply the inner retina are located in front of the photoreceptor layer, blocking access to light. Their shadows create a pattern of blindness in the field of vision that corresponds precisely to the location of the largest vessels in the eye. We show here that in squirrel monkeys, focal deprivation by blood vessels leads to rewiring of the eye's geniculocortical projections, imprinting an image of the retinal vascular tree onto the primary visual cortex. This process illustrates vividly that local imbalances in neuronal activity can influence column formation during normal development.

Animals↗

Effects of load manipulations, heart rate, and contractility on left ventricular apical rotation. An experimental study in anesthetized dogs.

BACKGROUND: Left ventricular twist or torsion has been defined as the counterclockwise rotation of the ventricular apex with respect to the base during systole. We have recently shown that since base rotation is minimal, measurement of apex rotation reflects the dynamics of left ventricular (LV) twist. Since the mechanisms by which load and contractility affect twist are controversial, we aimed to determine the relation between apex rotation and volume, contractility, and heart rate under conditions in which dimensions and pressures were accurately measured. METHODS AND RESULTS: Using our optical device coupled to the LV apex, apex rotation was recorded simultaneously with LV pressure, ECG, LV segment length, and minor-axis diameters (sonomicrometry) in 12 open-chest dogs. Using vena caval occlusion and volume loading, a linear end-diastolic (ED) relation between apex rotation and LV area index was obtained (slope, 0.61 +/- 0.06 degrees/percent change; intercept, -60.1 +/- 6.2 degrees; n = 10) that differed from the end-systolic (ES) relation (slope, 1.36 +/- 0.27 degree/percent change; intercept, -132.5 +/- 24.9 degrees; P < .005). With changes in contractility, afterload, or heart rate, for both ED and ES the apex rotation-volume points fell within the range of the relations established by changing preload, suggesting that volume is the major determinant of twist. Vena caval occlusion (preload and afterload decrease) caused an increase in amplitude of apex rotation, with maximal apex rotation occurring earlier in ejection. In contrast, acute volume loading (predominant preload increase) caused a small decrease in the amplitude of apex rotation, and twist relaxation was delayed into the isovolumic relaxation period. Likewise, with single-beat aortic occlusion (increased afterload), there was a slight decrease in the amplitude of apex rotation, and maximal apex rotation was delayed into the isovolumic relaxation period. Paired pacing (increased contractility) increased the total amplitude of apex rotation by 42% and caused a delay in untwisting until the end of the isovolumic relaxation period. An increase in heart rate over 150 beats per minute resulted in a significant decrease in the amplitude of apex rotation with a similar delay of twist relaxation into the isovolumic relaxation period. CONCLUSIONS: The effects of load, contractility, and heart rate manipulations on LV twist as measured throughout the cardiac cycle by the optical apex rotation method are manifested by changes in both the amplitude and dynamics of torsion. LV twist at ED and ES is primarily a function of volume; this relation appears to be unaltered by heart rate, afterload, and contractility. Whereas decreased load caused early untwisting, increases in preload, afterload, heart rate, and contractility caused a consistent pattern of delay in twist relaxation.

Anesthesia↗

New transcutaneous jaundice device with two optical paths.

OBJECTIVES: To confirm the accuracy and precision of transcutaneous bilirubin (TcB) values measured by a new device with two optical paths (JM-103) and the value of total serum bilirubin (TSB) level in clinical units of measurement. METHODS: For comparison of the levels of accuracy and precision of JM-103 and the old device (JM-102), serum samples were collected from 77 Japanese infants in three different hospitals including 24 preterm infants and 53 term infants. Measurement of TcB by JM-103 and JM-102 were performed on the forehead of each infant within 30 min before or after blood sampling. RESULTS: The range of TSB was limited to 19.6 mg/dL and to 17 mg/dL for preterm infants. The correlation coefficients for all subjects (r = 0.94) and for term and preterm subjects between TcB measured by JM-103 and TSB was higher than that between TcB measured by JM-102 and TSB. The regression line in term infants between TcB measured by JM-103 and TcB was similar to that in preterm infants. The error distribution of TcB measured by JM-102 and TSB for all subjects (0.00 +/- 2.21) and for term and preterm subjects was larger than that of TcB measured by JM-103 and TSB (all subjects, 0.30 +/- 1.55).

Bilirubin↗

ROC and CART analysis of subcutaneous adipose tissue topography (SAT-Top) in type-2 diabetic women and healthy females.

Women suffering from type-2 diabetes mellitus (NIDDM) show a more android fat pattern than healthy females, but to date no exact determination of their fat distribution differences exists. Measurements at 15 specified body sites with an optical device, the LIPOMETER, provide a subcutaneous adipose tissue topography (SAT-Top) of the individual. SAT-Top of 20 female NIDDM patients and 122 healthy controls was measured. ROC curve analysis was applied to evaluate the discriminative power of each body site and to provide cutoff values. Then a classification tree by the CART algorithm was established, showing SAT-Top differences between the two groups. Best discriminating results were achieved by the neck site (ROC area index = 0.76, sensitivity = 61.3%, specificity = 77.8%), the four sites of the thigh (area indices from 0.71 to 0.76), and a linear combination of all body sites stemming from a previous factor analysis, which provides condensed information of the extremities SAT-Top (area index = 0.80, sensitivity = 80.4%, specificity = 64.6%). The results could be improved by a summary measure of "android fat pattern" (area index = 0.89, sensitivity = 73.6%, specificity =88.3%) and a proportional measure of SAT-distribution, the relative neck (area index = 0.84, sensitivity = 83.0%, specificity = 70.5%). Overall, 136 (95.8%) of the 142 subjects were correctly classified by the classification tree (sensitivity = 75%, specificity = 99.2%). Both methods show the expected increased upper trunk obesity and decreased lower body obesity of NIDDM women compared with healthy females. Am. J. Hum. Biol. 12:388-394, 2000. Copyright 2000 Wiley-Liss, Inc.

Journal Article↗

Differences of subcutaneous adipose tissue topography in type-2 diabetic (NIDDM) women and healthy controls.

Women suffering from type-2 diabetes mellitus (non-insulin-dependent diabetes mellitus [NIDDM]) have more total body fat and upper body obesity compared with healthy controls. However, the standard measurement methods have disadvantages such as radiological burden, lack of precision, or high time consumption. A new optical device, the Lipometer, enables the noninvasive, quick, and save determination of the thickness of subcutaneous adipose tissue layers at any given site of the human body. The specification of 15 evenly distributed body sites allows the precise measurement of subcutaneous body fat distribution, so-called subcutaneous adipose tissue topography (SAT-Top). SAT-Tops of 20 women with clinically proven NIDDM and 122 healthy controls matched by age group were measured. In this paper, we describe the precise SAT-Top differences of these two groups and present the multidimensional SAT-Top information condensed in a two-dimensional factor plot and in a response plot of an artificial neural network. NIDDM women provide significantly lower leg SAT-Top and significantly higher upper trunk SAT-Top development ("apple"-type) compared with their healthy controls.

Adipose Tissue↗

Relationship between different subcutaneous adipose tissue layers, fat mass, and leptin in response to short-term energy restriction in obese girls.

This study addresses whether the expected relationship of 15 specified subcutaneous adipose tissue layers (SAT layers) from 1-neck to 15-calf and body fat mass (FM) with leptin was influenced by a weight-loss program. In 30 obese girls (10 prepubertal, 15 pubertal, and 5 late/postpubertal) SAT layers were measured by means of the optical device Lipometer. Fat mass (FM) was estimated indirectly by means of bioelectrical impedance. Leptin and insulin were determined by means of radioimmunoassays. All measurements were performed before (pre) and after (post) 3 weeks of low-caloric diet and physical training. At the beginning of the study, there were significant correlations for all estimates of adiposity and leptin (0.67 to 0.79; P < 0.0001). Five SAT layers from the upper body and the trunk (0.48 to 0.67; P < 0.01) but none from the abdominal region and lower extremities were correlated with leptin. FM together with SAT layers 4-upper back and 8-lower abdomen (negative slope) explained 79% of the variation in pre leptin values (P < 0.0001). The weight-loss program significantly reduced leptin (P < 0.0001), insulin (P = 0.04), estimates of adiposity (P < 0.0001), and SAT layers 4-upper back (P = 0.0006), 11-front thigh, 13-rear thigh, and 14-inner thigh (P between <0.03 and <0.01). Although significant, the reductions in the four SAT layers were small. Estimated fat-free mass was significantly increased after three weeks (P < 0.05). Changes in SAT layers from the upper extremities and from the trunk were inversely correlated to the decrease in leptin (P between <0.05 and <0.001). Initial leptin was the best correlate of the decrease in leptin (adj. R(2) = 0.815; P < 0.0001). However, when only changes in adiposity and insulin were considered in the regression model, changes in insulin contributed to the fall in leptin (adj. R(2) = 0.23; P = 0.004). When changes in SAT layers were added to the model, changes in SAT layers 2-triceps and 10-hip (negative slopes) contributed to the decrease in leptin (adj. R(2) = 0.48; P < 0.0001). After weight loss, correlations between estimates of post adiposity and post leptin (0.40, P = 0.01 to 0.57, P = 0.0005) were lower compared with pre values. SAT layers 4-upper back and 3-biceps contributed independently to post leptin values (adj. R(2) = 0.50; P < 0.0001). It is suggested that fat mass and SAT layers from the upper body are the main determinants of leptin in obese girls before weight loss. The diet and sports intervention program reduced leptin independent of the reduction in adiposity. The distribution of subcutaneous fat might be a stable correlate of circulating leptin after a short-term reduction in energy intake. Am. J. Hum. Biol. 12:803-813, 2000. Copyright 2000 Wiley-Liss, Inc.

Journal Article↗

Avian models of experimental myopia: environmental factors in the regulation of eye growth.

During normal development a precise match between the length of the path of light within the eye and the refractive state of the eye's optical elements is required for the retinal image to remain sharply in focus. Recent studies have shown that this match between eye growth and refractive state is partially under the control of environmental factors. Investigations in several species of ground-foraging birds have shown the existence of an optical mechanism that maintains the retinal image of the ground in focus on the upper retina without a change in accommodation, when the bird is standing erect. Moreover, as a young bird grows, the refractive state changes to maintain a sharp focus of the retinal image of the ground. These findings suggest that the quality of the retinal image may be an important regulator of the matching of refractive state to growth of the ocular globe. We have found in young, rapidly growing birds that the application of optical devices that degrade the quality of the retinal image interferes with the normal regulation of eye growth and results in excessive growth and severe myopia. Additional environmental variables that affect eye growth include nutritional deficiencies of calcium and vitamin D and elevated ocular temperature.

Animal Nutritional Physiological Phenomena↗

Android subcutaneous adipose tissue topography in lean and obese women suffering from PCOS: comparison with type 2 diabetic women.

The new optical device, the lipometer, enables the noninvasive, quick, safe, and precise determination of the thickness of subcutaneous adipose tissue (SAT) layers at any given site of the human body. Fifteen anatomically well-defined body sites from neck to calf describe a SAT topography (SAT-Top) like an individual "fingerprint" of a subject. This SAT-Top was examined in 16 women with polycystic ovary syndrome (PCOS) and compared to the body fat distribution of 87 age-matched healthy controls and 20 type-2 diabetic women. SAT-Top differences of these three groups were described and, to render the possibility of visual comparison, the 15-dimensional body fat information was condensed to a two-dimensional factor plot by factor analysis. All PCOS patients had an android body fat distribution with significantly thinner SAT layers on the legs as compared to healthy controls. Moreover, a hierarchical cluster analysis resulted in two distinctly different groups of PCOS women, a lean (PCOSL) and an obese (PCOSO) cluster: compared to healthy women, lean PCOS patients had significantly lower total SAT development, even though height, weight, and body mass index did not deviate significantly. Especially on the legs, their SAT layers were significantly lowered, indicating a more "apple-like" fat distribution type. Obese PCOS women showed a SAT-Top pattern very similar to that of women with type-2 diabetes, although the mean age difference between these groups was more than 30 years. Compared to healthy controls, the SAT-Top of these obese PCOS patients was strongly shifted into the android direction, appearing as "super-apples" with a significantly increased upper trunk obesity to 237.8% and a significantly decreased leg SAT development to 79.8%.

Adipose Tissue↗

Kinetics study of Bungarus fasciatus venom acetylcholinesterase immobilised on a Langmuir-Blodgett proteo-glycolipidic bilayer.

This study deals with the kinetics properties of an enzyme immobilised in a defined orientation in a biomimetic environment. For this purpose, acetylcholinesterase (AChE) was captured at the surface of a nanostructured proteo-glycolipidic Langmuir-Blodgett film through specific recognition by a noninhibitor monoclonal antibody (IgG) inserted in a neoglycolipid bilayer. Modelling of this molecular assembly provided a plausible interpretation of the functional orientation of the enzyme. The AChE activity being stable for several weeks, the enzyme kinetics were investigated, and fitted perfectly with heterogeneous biocatalytic behaviour representative of cellular enzymatic catalysis. The AChE-IgG-glycolipid nanostructure was directly interfaced with an efficient optical device. Such an association, leading to an intimate contact between the nanostructure and the biochemical signal transducer, gives direct access to the intrinsic AChE behaviour. This study thus demonstrates the potential for direct investigation of the kinetic behaviour of an immobilised enzyme on a lipid bilayer through an efficient transduction system.

Acetylcholinesterase↗

Supercritical fluid synthesis of metal and semiconductor nanomaterials.

In the near future physical and economic constraints are expected to limit the continued miniaturisation of electronic and optical devices using current "top-down" lithography-based methods. Consequently, nonlithographic methods for synthesising and organising materials on the nanometre scale are required. In response to these technological needs a number of research groups are developing new supercritical fluids methodologies to synthesise and self-assemble "building blocks" of nanomaterials, from the "bottom-up", into structurally complex device architectures. This concept paper highlights some of the recent advances in the synthesis of metal and semiconductor nanoparticles and nanowires by using supercritical fluids. In addition, we describe an efficient supercritical fluid approach for constructing ordered arrays of metal and semiconductor nanowires within mesoporous silica templates.

Journal Article↗

Oxasmaragdyrin-ferrocene and oxacorrole-ferrocene conjugates: synthesis, structure, and nonlinear optical properties.

Ferrocenyl macrocyclic conjugates involving 22 pi oxasmaragdyrins and 18 pi oxacorroles have been synthesized and characterized. The direct covalent linkage of the ferrocenyl moiety to the meso position of the macrocycle is achieved by simple oxidative coupling of appropriate precursors with trifluoroacetic acid as catalyst. The electronic coupling between the ferrocenyl moiety and the macrocyclic pi system is apparent from: a) the red shifts (293-718 cm(-1)) of the Soret and Q-bands in the electronic absorption spectra of ferrocenyl conjugates; b) the shift of oxidation potentials (50-130 mV) of both the ferrocene and the corrole rings to the positive potentials; and c) considerable shortening of the C-C bond which connects the ferrocene and the meso-carbon atom of the macrocycle. The single-crystal X-ray structure of oxasmaragdyrin-ferrocene conjugate 9 reveals the planarity of the 22 pi skeleton with very small deviations of the meso-carbon atoms. The meso-ferrocenyl substituent has a small dihedral angle of 38 degrees, making way for mixing of the molecular orbitals of the ferrocene and the macrocycle. However, the other two meso substituents are almost perpendicular to the mean plane, defined by the three meso carbon atoms. Classical C-H...O and nonclassical C-H...pi interactions lead to a two-dimensional supramolecular network. Ferrocene-smaragdyrin conjugate 9 bonds to a chloride ion in the protonated form and a rhodium(i) ion in the free base form. Nonlinear optical measurements reveal a larger nonlinear refractive index (-5.83 x 10(-8)cm(2)W(-1)) and figure of merit (2.28 x 10(-8)cm(3)W(-1)) for the rhodium smaragdyrin-ferrocene conjugate 19 than for the others, suggesting its possible application in optical devices.

Journal Article↗

Design of molecular photonic wires based on multistep electronic excitation transfer.

Light-harvesting complexes, one of nature's supreme examples of nanoscale engineering, have inspired researchers to construct molecular optical devices, such as photonic wires, which are optimised for efficient transfer of excited-state energy over large distances. The control parameters for the design and the advantages of single-molecule fluorescence spectroscopy for the study of such complex systems are discussed with respect to energy-transfer mechanisms, chromophore selection and arrangement as well as static and dynamic heterogeneity.

Journal Article↗