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We are interested in clinical implications of adaptation to blurred and sharpened images. Therefore, we investigated repeatability, individual variability and characteristics of the adaptation curves of 39 normally-sighted individuals. The point of subjective neutrality (PSN - the slope of the spatial spectrum of the image that appears normal) following adaptation was measured for each adaptation level and was used to derive individual adaptation curves for each subject. Adaptation curves were fitted with a modified Tukey biweight function as the curves were found to be tumbled-S shaped and asymmetrical for blur and sharp in some subjects. The adaptation curve was found to be an individual characteristic as inter-subject variability exceeds test/re-test variability. The existence of individual variability may have implications for the prescription and clinical success of optical devices as well as image enhancement rehabilitation options., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: Amyotrophic Lateral Sclerosis (ALS) treatment is complicated by the various mechanisms underlying motor neuron degeneration. Recent studies showed that the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) are compromised in an animal model of ALS due to endothelial cell degeneration. A later study demonstrated a loss of endothelium integrity in the spinal cords of ALS patients. Since circulating endothelial cells (CECs) in the peripheral blood are associated with endothelium damage, being detached dysfunctional endothelial cells, we hypothesized that CEC levels may reflect endothelium condition in ALS patients., Methodology/principal Findings: CEC levels were estimated in whole blood smears from ALS patients with moderate stage ((M)ALS), severe stage ((S)ALS), and healthy controls by CD146 expression using immunocytochemistry. A significant reduction of CECs was detected in (M)ALS and (S)ALS patients., Conclusions/significance: CECs did not predict endothelium state in ALS patients; however, endothelial damage and/or impaired endothelium repair may occur in ALS leading to BBB/BSCB dysfunction. Reduced CECs in peripheral blood of ALS patients may indicate different mechanisms of endothelial damage and repair, rather than only detachment of dysfunctional endothelial cells. Although a potential mechanism of CEC reduction is discussed, establishing a reliable indicator of endothelial dysfunction/damage is important for evaluation of BBB/BSCB status in ALS patients during disease progression.

Severe visual field constriction (tunnel vision) impairs the ability to navigate and walk safely. We evaluated Trifield glasses as a mobility rehabilitation device for tunnel vision in an extended wearing trial. Twelve patients with tunnel vision (5-22 degrees wide) due to retinitis pigmentosa or choroideremia participated in the 5-visit wearing trial. To expand the horizontal visual field, one spectacle lens was fitted with two apex-to-apex prisms that vertically bisected the pupil on primary gaze. This provides visual field expansion at the expense of visual confusion (two objects with the same visual direction). Patients were asked to wear these spectacles as much as possible for the duration of the wearing trial (median 8, range 6-60 weeks). Clinical success (continued wear, indicating perceived overall benefit), visual field expansion, perceived direction and perceived visual ability were measured. Of 12 patients, nine chose to continue wearing the Trifield glasses at the end of the wearing trial. Of those nine patients, at long-term follow-up (35-78 weeks), three reported still wearing the Trifield glasses. Visual field expansion (median 18, range 9-38 degrees) was demonstrated for all patients. No patient demonstrated adaptation to the change in visual direction produced by the Trifield glasses (prisms). For reported difficulty with obstacles, some differences between successful and non-successful wearers were found. Trifield glasses provided reported benefits in obstacle avoidance to 7 of the 12 patients completing the wearing trial. Crowded environments were particularly difficult for most wearers. Possible reasons for long-term discontinuation and lack of adaptation to perceived direction are discussed.

People with severely restricted peripheral visual fields have difficulty walking confidently and safely in the physical environment. Augmented vision devices that we are developing for low-vision rehabilitation implement vision multiplexing, providing two views of the same scene at two different scales (sizes), with a cartooned minified wide view overlaying a natural see-through view. Inattentional blindness may partially limit the utility of these devices as low-vision aids. Inattentional blindness, the apparent inability to notice significant but unexpected events in an unattended scene when attention is fixed on another scene, has classically been demonstrated by overlaying two unrelated game scenes, with unexpected events occurring in one scene while attention is maintained on the other scene by a distractor task. We hypothesized that context like that provided by the related wide view in our devices might mitigate inattentional blindness in a study with two simultaneous views of the same scene shown at different scales. It did not, and unexpected event detection rates were remarkably consistent with our and other mixed-scene studies. Still, detecting about half of the unexpected events bodes well for our use of vision aids that employ vision multiplexing. Without the aids, is it likely that many more events would be missed.

It can be useful to present a different image to each of the two eyes while they cooperatively view the world. Such dichoptic presentation can occur in investigations of stereoscopic and binocular vision (e.g., strabismus, amblyopia) and vision rehabilitation in clinical and research settings. Various techniques have been used to construct dichoptic displays. The most common and most flexible modern technique uses liquid-crystal (LC) shutters. When used in combination with cathode ray tube (CRT) displays, there is often leakage of light from the image intended for one eye into the view of the other eye. Such interocular crosstalk is 14% even in our state of the art CRT-based dichoptic system. While such crosstalk may have minimal impact on stereo movie or video game experiences, it can defeat clinical and research investigations. We use micromirror digital light processing (DLP) technology to create a novel dichoptic visual display system with substantially lower interocular crosstalk (0.3%; remaining crosstalk comes from the LC shutters). The DLP system normally uses a color wheel to display color images. Our approach is to disable the color wheel, synchronize the display directly to the computer's sync signal, allocate each of the three (former) color presentations to one or both eyes, and open and close the LC shutters in synchrony with those color events.

Purpose: A device was developed to provide an expanded visual field to patients with tunnel vision by superimposing minified edge images of the wide scene, in which objects appear closer to the heading direction than they really are. Experiments were conducted in a virtual environment to determine whether users would overestimate collision risks., Methods: Given simulated scenes of walking or standing with intention to walk toward a given direction (intended walking) in a shopping mall corridor, participants (12 normally sighted and 7 with tunnel vision) reported whether they would collide with obstacles appearing at different offsets from variable walking paths (or intended directions), with and without the device. The collision envelope (CE), a personal space based on perceived collision judgments, and judgment uncertainty (variability of response) were measured. When the device was used, combinations of two image scales (5x minified and 1:1) and two image types (grayscale or edge images) were tested., Results: Image type did not significantly alter collision judgment (P > 0.7). Compared to the without-device baseline, minification did not significantly change the CE of normally sighted subjects for simulated walking (P = 0.12), but increased CE by 30% for intended walking (P < 0.001). Their uncertainty was not affected by minification (P > 0.25). For the patients, neither CE nor uncertainty was affected by minification (P > 0.13) in both walking conditions. Baseline CE and uncertainty were greater for patients than normally sighted subjects in simulated walking (P = 0.03), but the two groups were not significantly different in all other conditions., Conclusions: Users did not substantially overestimate collision risk, as the x5 minified images had only limited impact on collision judgments either during walking or before starting to walk.

With the aging of the population, the prevalence of eye diseases and thus of vision impairment is increasing. The TV watching habits of people with vision impairments are comparable to normally sighted people1, however their vision loss prevents them from fully benefiting from this medium. For over 20 years we have been developing video image-enhancement techniques designed to assist people with visual impairments, particularly those due to central retinal vision loss. A major difficulty in this endeavor is the lack of evaluation techniques to assess and compare the effectiveness of various enhancement methods. This paper reviews our approaches to image enhancement and the results we have obtained, with special emphasis on the difficulties encountered in the evaluation of the benefits of enhancement and the solutions we have developed to date.

In heart failure (HF), sympathetic nerve activity is increased. Measurements in HF patients of cardiac norepinephrine spillover, reflecting cardiac sympathetic nerve activity (CSNA), indicate that it is increased earlier and to a greater extent than sympathetic activity to other organs. This has important consequences because it worsens prognosis, provoking arrhythmias and sudden death. To elucidate the mechanisms responsible for the activation of CSNA in HF, we made simultaneous direct neural recordings of CSNA and renal SNA (RSNA) in two groups of conscious sheep: normal animals and animals in HF induced by chronic, rapid ventricular pacing. In normal animals, the level of activity, measured as burst incidence (bursts of pulse related activity/100 heart beats), was significantly lower for CSNA (30 +/- 5%) than for RSNA (94 +/- 2%). Furthermore, the resting level of CSNA, relative to its maximum achieved while baroreceptors were unloaded by reducing arterial pressure, was set at a much lower percentage than RSNA. In HF, burst incidence of CSNA increased from 30 to 91%, whereas burst incidence of RSNA remained unaltered at 95%. The sensitivity of the control of both CSNA and RSNA by the arterial baroreflex remained unchanged in HF. These data show that, in the normal state, the resting level of CSNA is set at a lower level than RSNA, but in HF, the resting levels of SNA to both organs are close to their maxima. This finding provides an explanation for the preferential increase in cardiac norepinephrine spillover observed in HF.

Arterial baroreflex function diminishes with age, but whether cardiopulmonary vagal reflexes are similarly altered with physiological aging has not been fully elucidated. In this study, predominantly cardiac high pressure mechanoreceptor-activated (ramp baroreflex) and cardiopulmonary chemoreceptor-activated (von Bezold-Jarisch reflex) vagal reflexes in conscious, instrumented rats were impaired by 30% to 40% (P<0.05) in 24-month-old (n=12) compared with 6-month-old rats (n=12). To determine whether this is a restorable deficit, the influence of atrial natriuretic peptide (ANP), either by infusion or blockade of its breakdown, was studied. ANP infusion was previously shown to enhance Bezold-Jarisch reflex and ramp baroreflex bradycardia in young adult rats. The present study confirmed that vagal reflex augmentation by ANP (50 pmol/kg per minute) also occurs in old rats (increased by 60+/-18% (Bezold-Jarisch reflex) and 91+/-15% (ramp baroreflex; P<0.05). Direct vagal stimulation in anesthetized animals showed that the target for ANP was not the cardiac vagus itself in old rats (n=7), although in young rats only, we confirmed the published finding that ANP enhances vagal bradycardia (by 58+/-14%, n=7). Neutral endopeptidase 24.11 degrades ANP and several other peptides. The neutral endopeptidase inhibitor candoxatrilat (5 mg/kg per day IV for 7 to 9 days) restored vagal reflex bradycardia in old rats (n=6) to levels similar to those in young neutral endopeptidase inhibitor-treated rats (n=6). Impaired cardiopulmonary vagal reflex control of heart rate is thus a feature of normal aging, and this deficit may be ameliorated by either ANP infusion or chronic neutral endopeptidase inhibition.

Augmented-vision devices that we are developing to aid people with low vision (impaired vision) employ vision multiplexing- the simultaneous presentation of two different views to one or both eyes. This approach enables compensation for vision deficits without depriving the wearers of their normal views of the scene. Ideally, wearers would make use of the simultaneous views to alert them to potential mobility hazards, without a need to divide attention consciously. Inattentional blindness, the frequent inability to notice otherwise-obvious events in one scene while paying attention to another, overlapping, scene, works against that sort of augmentation, so we are investigating ways to mitigate it. In this study, we filtered the augmented view, creating cartoon-like representations, to make it easier to detect significant features in that view and to minimise interference with the normal view. We reproduced a classic inattentional blindness experiment to evaluate the effect, and found that, surprisingly, edge filtering had no detectable effect - positive or negative - on the noticing of unexpected events in the unattended scene. We then modified the experiment to determine if the inattentional blindness was because of the confusion of overlaid views or simply a matter of attention, and found the latter to be the case.

Purpose: To investigate the appearance of limbal and bulbar hyperaemia in normal eyes, their relationship and the inter-observer agreement of clinical grading., Methods: The right eyes of 120 healthy, non-contact lens-wearing subjects (m = 57, f = 63, median age = 45 years, range 18-77 years) were examined by two trained observers. Limbal and bulbar hyperaemia were scored using the Cornea and Contact Lens Research Unit (CCLRU) redness grading scales interpolated into 0.1 increments. Redness of four quadrants, and overall, were assessed, and quadrant-average redness was calculated. Inter-observer agreement was assessed at the start and end of the study (20 subjects each)., Results: For limbal redness, the overall (1.62 +/- 0.46) (mean units +/- S.D.) was not significantly different from the quadrant-average (1.61 +/- 0.40) score. For bulbar redness, the overall (2.02 +/- 0.49) was higher than the quadrant-average (1.82 +/- 0.39) score (p < 0.0001). Significant correlations were found between bulbar and limbal quadrants (Pearson: r > or = 0.43, p < 0.0001). Significant differences in redness were found between quadrants (p < 0.0001), with nasal and temporal redder than superior and inferior quadrants. Small effects of age and gender were found for limbal redness. The inter-observer 95% limits of agreement were similar at the start and end of the study. They were larger for overall (0.57) compared with quadrant-average (0.28) redness., Conclusions: For similar populations, a limbal redness above 2.5 or a bulbar redness above 2.6 (quadrant-average) or 3.0 (overall) may be considered abnormal. Limbal and bulbar redness were correlated. Quadrant-average scores are recommended instead of overall scores, as inter-observer agreement was better.

We used a new method to measure the perceived quality of contrast-enhanced motion video. Patients with impaired vision (n=24) and normally sighted subjects (n=6) adjusted the level of MPEG-based enhancement of 8 videos (4 min each) drawn from 4 categories. They selected the level of enhancement that provided the preferred view of the videos, using a decreasing-step-size staircase procedure. Most patients made consistent selections of the preferred level of enhancement, indicating an appreciation of and a perceived benefit from the MPEG-based enhancement. The selections varied between patients and were correlated with letter contrast sensitivity, but the selections were not affected by training, experience, or video category. We measured just noticeable differences directly for videos and mapped the image manipulation (enhancement in our case) onto an approximately linear perceptual space. These tools and approaches will be of value in other evaluations of the image quality of motion video manipulations.

Intravenous B-type natriuretic peptide (BNP) enhances the bradycardia of reflexes from the heart, including the von Bezold-Jarisch reflex, but its site of action is unknown. The peptide is unlikely to penetrate the blood-brain barrier but could act on afferent or efferent reflex pathways. To investigate the latter, two types of experiment were performed on urethane-anesthetized (1.4 g/kg iv) rats. First, the activity was recorded extracellularly from single cardiac vagal motoneurons (CVMs) in the nucleus ambiguus. CVMs were identified by antidromic activation from the cardiac vagal branch and by their barosensitivity. Phenyl biguanide (PBG), injected via the right atrium in bolus doses of 1-5 mug to evoke the von Bezold-Jarisch reflex, caused a dose-related increase in CVM activity and bradycardia. BNP infusion (25 pmol.kg(-1).min(-1) iv) significantly enhanced both the CVM response to PBG (n = 5 rats) and the reflex bradycardia, but the log-linear relation between those two responses over a range of PBG doses was unchanged by BNP. The reflex bradycardia was not enhanced in five matched time-control rats receiving only vehicle infusions. In five other rats the cervical vagi were cut and the peripheral right vagus was stimulated supramaximally at frequencies of 1-20 Hz. The bradycardic responses to these stimuli were unchanged before, during, and after BNP infusion. We conclude that systemic BNP in a moderate dose enhances the von Bezold-Jarisch reflex activation of CVM, in parallel with the enhanced reflex bradycardia. That enhancement is due entirely to an action before the vagal efferent arm of the reflex pathway.

The von Bezold-Jarisch reflex (BJR) is a vagally mediated chemoreflex from the heart and lungs, causing hypopnea, bradycardia, and inhibition of sympathetic vasomotor tone. However, cardiac sympathetic nerve activity (CSNA) has not been systematically compared with vasomotor activity during the BJR. In 11 urethane-anesthetized (1-1.5 g/kg iv), artificially ventilated rats, we measured CSNA simultaneously with lumbar sympathetic activity (LSNA) while the BJR was evoked by right atrial bolus injections of phenylbiguanide (0.5, 1.0, 1.5, and 2 microg). Nerve and heartbeat responses were analyzed by calculating normalized cumulative sums. LSNA and heartbeats were always reduced by the BJR. An excitatory "rebound" component often followed the inhibition of LSNA but never outweighed it. For CSNA, however, excitation usually (in 7 of 11 rats) outweighed any initial inhibition, such that the net response to phenylbiguanide was excitatory. The differences in net response between LSNA, CSNA, and heartbeats were all significant (P < 0.01). A second experimental series on seven rats showed that methyl atropine (1 mg/kg iv) abolished the bradycardia of the BJR, whereas subsequent bilateral vagotomy substantially reduced LSNA and CSNA responses, both excitatory and inhibitory. These findings show that, during the BJR, 1) CSNA is often excited, 2) there may be coactivation of sympathetic and parasympathetic drives to the heart, 3) divergent responses may be evoked simultaneously in cardiac vagal, cardiac sympathetic, and vasomotor nervous pathways, and 4) those divergent responses are mediated primarily by the vagi.

Magnification around the most important point of a movie scene (center of interest-COI) might aid people with visual impairments that cause resolution loss. This will be effective only if most people look at the same place when watching a movie. We recorded the eye movements of 20 normally sighted subjects as each watched six movie clips, totaling 37.5 min. More than half of the time the distribution of subject gaze points fell within an area statistic that was less than 12% of the movie scene. Male and older subjects were more likely to look in the same place than female and younger subjects, respectively. We conclude that the between-subject agreement is sufficient to make the approach practical.

Purpose: To quantify the level of normal bulbar conjunctival hyperaemia using the Cornea and Contact Lens Research Unit (CCLRU) grading scale, and to investigate inter-observer agreement., Methods: Bulbar conjunctival hyperaemia was assessed by two trained observers, using the CCLRU grading scale (zero to four units) interpolated into 0.1 increments, on the right eye of 121 healthy, non-contact lens-wearing subjects (male=58, female=63, median age=28 years, range 16-77). The eye was observed using a slit-lamp bio-microscope (x 10 magnification) under diffuse, white illumination. The subject's position of gaze was directed to allow grading of four quadrants: superior, nasal, inferior, and temporal conjunctiva. Bulbar redness was defined as the average of those four grades of conjunctival hyperaemia. A further twenty subjects were recruited to assess inter-observer agreement (male=8, female=12, median age=23 years)., Results: The average bulbar redness was 1.93 (+/-0.32 SD) units. The nasal (2.3+/-0.4) and temporal (2.1+/-0.4) quadrants were significantly redder than the superior (1.6+/-0.4) and inferior (1.7+/-0.4) quadrants (P<0.0001). Males had redder eyes than females by 0.2 units. Inter-observer 95% limits of agreement for bulbar redness was 0.38 units., Conclusions: The average bulbar redness of 1.9 units was higher than expected, reflecting the design of the grading scale. A bulbar redness of greater than 2.6 units may be considered abnormal, and a change in bulbar redness of > or =0.4 units may be significant.

Virtual environments (VEs) allow safe, repeatable, and controlled evaluations of obstacle avoidance and navigation performance of people with visual impairments using visual aids. Proper simulation of mobility in a VE requires an interface, which allows subjects to set their walking pace. Using conventional treadmills, the subject can change their walking speed by pushing the tread with their feet, while leveraging handrails or ropes (self-propelled mode). We developed a feedback-controlled locomotion interface that allows the VE workstation to control the speed of the treadmill, based on the position of the user. The position and speed information is also used to implement automated safety measures, so that the treadmill can be halted in case of erratic behavior. We compared the feedback-controlled mode to the self-propelled mode by using speed-matching tasks (follow a moving object or match the speed of an independently moving scene) to measure the efficacy of each mode in maintaining constant subject position, subject control of the treadmill, and subject pulse rates. Additionally, we measured the perception of speed in the VE on each mode. The feedback-controlled mode required less physical exertion than self-propelled. The average position of subjects on the feedback-controlled treadmill was always within a centimeter of the desired position. There was a smaller standard deviation in subject position when using the self-propelled mode than when using the feedback-controlled mode, but the difference averaged less than six centimeters across all subjects walking at a constant speed. Although all subjects underestimated the speed of an independently moving scene at higher speeds, their estimates were more accurate when using the feedback-controlled treadmill than the self-propelled.

Color matches made with a Nagel anomaloscope are used in the differentiation of color vision deficiencies. When these color matches are made over a wide range of retinal illuminances, the changes in the color match provide information about the regeneration kinetics and the absorption spectra of the middle- and long-wavelength cone photopigments. These steady-state color matches vary with a variety of conditions, and may have value in screening for eye disease. Recently, high-brightness LEDs have become available that allowed us to construct a LED-based, high-brightness anomaloscope. We used inexpensive, low-energy components to replicate an earlier instrument, getting a maximum retinal illuminance over 5.6 log Trolands.

Objective: Neutral endopeptidase (NEP, EC 3.4.24.11) metabolises endogenous vasoactive peptides that may protect against atherogenesis. Since NEP is found in the adventitia of arteries, we investigated the anti-atherogenic effects of chronic adventitial NEP inhibition., Methods: Intimal hyperplasia of rabbit carotid arteries was induced by placement of soft, non-occlusive, peri-arterial silastic collars. NEP localisation was studied with autoradiography 7 and 14 days after collar placement. Vascular NEP was inhibited in vivo by local superfusion of one collared carotid artery with Candoxatrilat (50 pmol/h), for 7 days (n = 7). The contralateral collar was filled with saline vehicle. After 7 days, ring segments of collared and normal (proximal to the collar) arteries were obtained and in vitro functional measurements, immunohistochemical determination of the pro-atherogenic factor plasminogen activator inhibitor-1 (PAI-1), localization of macrophages and morphometric analyses were carried out., Results: Vascular NEP radiolabelled substrate binding, mainly in the media, was increased by approximately 50% after 7 days (n = 5; p < 0.05) and by approximately 300% after 14 days of collar placement (n = 5; p < 0.05). Compared with normal artery segments from the same animal, vehicle-filled collared sections displayed significantly impaired vasorelaxation to acetylcholine (endothelium-independent vasodilatation was preserved), increased PAI-1 immunostaining, macrophage accumulation and intimal thickening. In Candoxatrilat-treated collared arteries, vasorelaxation to acetylcholine was improved, along with reductions in PAI-1 levels, macrophage numbers and intimal area (all p < 0.05)., Conclusion: Enhancing the activity of local, endogenous peptides by adventitial inhibition of vascular NEP may protect against early atherogenesis. This is of particular relevance to using adventitial therapies to prevent intimal hyperplasia leading to restenosis.

A significant proportion of aged humans may have impaired thirst and inadequate fluid intake after a period of fluid deprivation. We have studied the water drinking responses, relative to body weight, of Munich Wistar (MW) rats in response to osmotic, hypovolemic, dehydrational, and angiotensin (Ang)-related stimuli as they aged from 3 to 24 months. Young 3-months-old (m.o.) rats had the largest daily fluid intakes and drinking responses to hypertonic and dehydrational stimuli, suggesting that they have accentuated thirst in comparison with older age groups. There were no differences in daily fluid intake from 6-24 m.o.; however, drinking responses to i.p. injection of hypertonic 0.4 mol/liter NaCl gradually declined over this period so that in 24-m.o. rats the response was only half that of 6-m.o. rats. Water intake after 24-h water deprivation also declined gradually over 24 months. Drinking responses to hypovolemia induced by s.c. injection of colloid (polyethylene glycol) were unchanged in 6- to 15-m.o. rats, then declined precipitously in 18- to 24-m.o. rats. Drinking responses to s.c. Ang II or s.c. isoproterenol were not reduced in 24-m.o. rats, nor was the drinking associated with feeding. Therefore, there are specific impairments of water intake in response to hypertonicity and hypovolemia in aged MW rats, but Ang-related drinking is not reduced. Like aged humans, aged MW rats exhibit high plasma atrial natriuretic peptide levels and impaired cardiovascular reflexes that could contribute to the impairment of thirst with age.

Objective: Elevated vascular plasminogen activator inhibitor-1 (PAI-1) levels are associated with atherosclerosis. In vitro, C-type natriuretic peptide (CNP) has anti-proliferative effects and inhibits the production of PAI-1 in cultured vascular cells. Whether CNP can affect PAI-1 in vivo, particularly in the setting of atherosclerosis, has not been reported., Methods: Using the rabbit carotid arterial collar model of intimal hyperplasia (collar in place for 7 days), PAI-1 protein was compared in normal, vehicle (saline)-collared, and CNP-treated-collared arteries from the same animal. PAI-1 levels were measured by immunohistochemistry and densitometry and by Western blot. CNP was either infused into the peri-arterial space within one collar (10 fmol/h) or infused directly into the arterial lumen under one collar (100 pmol/h). In some rabbits (n=8), superoxide production in collared and normal artery segments was measured in vitro by chemiluminescence., Results: PAI-1 was present throughout the vascular wall. Endothelial PAI-1 was elevated in saline-collared arteries (approximately 16%, P<0.05; n=7 rabbits) compared with normal carotid segments. The collar induced both a neointima that contained PAI-1 and the accumulation of macrophages in the adventitia. Peri-arterial CNP reduced PAI-1 (P<0.05) in the endothelium (33%), adventitia (47%) and neointima (39%), compared with levels in the contralateral, saline-collared carotid artery, while macrophage infiltration was reduced. Elevated superoxide production in collared arteries was not altered by chronic in vivo treatment with CNP (n=8). Peri-arterial CNP treatment did not reduce intimal thickening. Intra-luminal CNP (n=6) reduced endothelial, neointimal and total vessel (Western blot) PAI-1, macrophage accumulation, and intimal thickening (all P<0.05)., Conclusions: CNP treatment of collared carotid arteries in vivo for 1 week suppressed endothelial and neointimal PAI-1, independently of intimal thickening. The CNP effects were not via superoxide. This is the first evidence that CNP inhibits activated PAI-1, in vivo.

Background: Atrial and C-type natriuretic peptides (ANP and CNP), acting through different receptors, have antiproliferative effects in vitro. Beneficial effects of CNP in vivo on early atherosclerosis have been described, but it is not known if ANP is antiproliferative in vivo. In the present study, the effects of chronic in vivo ANP were tested and compared with CNP on endothelial dysfunction and intimal thickening caused by peri-arterial collars., Methods: Non-occlusive collars were placed bilaterally around the common carotid arteries of rabbits. One collar was filled with saline vehicle. The contralateral collar was filled with ANP or CNP (1 or 10 microM, n = 5-7) with slow replacement of peptide via mini-pump (1 or 10 fmol/h)., Results: After 7 days, endothelium-dependent vasorelaxation in saline-collared arteries was 33 +/- 3% of maximum [averaged over 0.03-1 muM acetylcholine (ACh)] compared to 64 +/- 2% in normal (uncollared) arteries (p < 0.05, n = 23). In vivo ANP restored the ACh relaxation to normal (e.g., 57 +/- 6%, 1 microM ANP), similar to effects seen with CNP in vivo. Endothelium-independent vasorelaxation of collared-vessels was not altered by either peptide. Intimal hyperplasia induced by the collars was not prevented by peri-arterial natriuretic peptides. In additional rabbits (n = 6), CNP (100 pmol/h) given directly into the lumen of collared carotid arteries for 7 days reduced neointima formation by 16 +/- 5% (p < 0.05), whereas ANP given intraluminally (100 pmol/h; n = 6) did not., Conclusions: The more potent actions of CNP on vascular smooth muscle cell migration and proliferation (established in vitro) may explain differences between the peptides on intimal hyperplasia in vivo. The major hallmark of atherosclerosis and restenosis, endothelial dysfunction, was prevented by chronic, peri-arterial administration of ANP or CNP., (Copyright 2005 S. Karger AG, Basel.)

Psychophysicists use spatial or temporal two-alternative forced-choice (2AFC) paradigms interchangeably. Thus, experiments with the same general goal are carried out using one or the other paradigm by distinct or even the same research groups. For example, this situation has occurred both in studies on visual sensitivity in dyslexia and in studies on lateral interactions in peripheral vision. Conflicting results in either field (e.g. whether or not dyslexics have a visual deficit and whether or not peripheral detection is facilitated by the presence of flankers) appear to be resolved on the surmise that spatial and temporal 2AFC paradigms indeed produce different results. We designed experiments in which peripheral detection thresholds for Gabor patches (in the presence or absence of suprathreshold flankers) could be measured using completely equivalent spatial and temporal 2AFC paradigms so that any resultant difference can be unequivocally attributed to the effect of the paradigms themselves. The results showed that spatial 2AFC renders significantly lower sensitivity than temporal 2AFC when the target is presented along with suprathreshold flankers, but about the same sensitivity as temporal 2AFC when the target is presented alone. In the end, this resulted in statistically significant facilitation in peripheral vision only when measured with temporal 2AFC. Separate experiments at each of several peripheral locations revealed that the presence and magnitude of this effect varies not only with psychophysical paradigm but also with retinal locus.

Foveal detection of a Gabor patch (target) is facilitated by collinear, displaced high-contrast flankers. Polat and Sagi reported that the same phenomenon occurred in the periphery, but no data were presented [Proc. Natl. Acad. Sci. 91 (1994) 1206]. Others have found no facilitation in a limited number of conditions tested. To resolve this apparent conflict, we measured lateral facilitation in the near-periphery using a range of stimulus parameters. We found facilitation for a range of target-flanker distances for peripheral eccentricities up to 6 degrees , but the magnitude of the effect was less than found in central vision. Facilitation varied across subjects and with spatial frequency. Flanker contrast had no effect over the range evaluated (10-80%). Equal facilitation was found for two global arrangements of the stimulus pattern. Facilitation was found using a temporal, but not a spatial two-alternative forced-choice paradigm, accounting for the different results among previous studies. This finding supports previous indications of the role of attention in altering such facilitation. The value of facilitation from lateral interactions for persons with central vision impairment, who have to shift their attention to a peripheral locus constantly, needs to be examined.

This article describes a system for tracking the line of primary gaze (LoPG) of participants as they view a large projection screen. Using a magnetic head tracker and a tracking algorithm, we find the onscreen location at which a participant is pointing a head-mounted crosshair. The algorithm presented for tracking the LoPG uses a polynomial function to correct for distortion in magnetic tracker readings, a geometric model for computing LoPG from corrected tracker measurements, and a method for finding the intersection of the LoPG with the screen. Calibration techniques for the above methods are presented. The results of two experiments validating the algorithm and calibration methods are also reported. Experiments showed an improvement in accuracy of LoPG tracking provided by each of the two presented calibration steps, yielding errors in LoPG measurements of less than 2 degrees over a wide range of head positions. Source code for the described algorithms can be downloaded from the Psychonomic Society Web archive, http://www.psychonomic.org/archive/.

1. If one was to design a hormone to protect the heart, it would have a number of features shown by the cardiac natriuretic peptides atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP). These hormones are made in cardiomyocytes and are released into the circulation in response to atrial and ventricular stretch, respectively. Atrial natriuretic peptide and BNP can reduce the preload and after-load in normal and failing hearts. They reduce blood volume over the short term by sequestering plasma and over the longer term by promoting renal salt and water excretion and by antagonizing the renin-angiotensin-aldosterone system at many levels. Each of these actions affords indirect benefit to a volume- or pressure-threatened heart. 2. Recent studies have identified additional modes of action of the natriuretic peptides that may also confer cardioprotective benefits, especially in heart disease. The emerging findings are: (i) that ANP and BNP antagonize the cardiac hypertrophic action of angiotensin II and continue working under conditions where endothelial nitric oxide (NO) function is compromised, such as in the presence of high glucose in diabetes; (ii) they potentiate the bradycardia caused by inhibitory ('autoprotective') cardio-cardiac reflexes; and, furthermore, (iii) BNP can suppress cardiac sympathetic nerve activity in humans, including those with heart failure. Thus, it appears that natriuretic peptides can shift sympathovagal balance in a beneficial direction (away from the sympathetic). The vagal reflex and antihypertrophic actions of the peptides are mediated by particulate guanylyl cyclase (pGC) natriuretic peptide receptors. 3. The multiple synergistic actions of the natriuretic peptides make them and their pGC receptors attractive targets for therapy in heart disease. Encouragingly, exogenous natriuretic peptides remain effective even when endogenous peptide levels are raised, as is the case in heart failure. They also remain effective in disease states where other protective mechanisms, such as the NO system, have become ineffective, offering yet further encouragement for the therapeutic use of the natriuretic peptides.

While atrial and B-type natriuretic peptides (ANP and BNP) have been shown to enhance reflex responses attributed to cardiac vagal afferents, their effects on arterial baroreceptor reflex function remain controversial. The actions of C-type natriuretic peptide (CNP) in this regard are unknown. To clarify their actions on arterial baroreflexes, we tested whether i.v. infusions of ANP, BNP or CNP at 10 pmol kg(-1) min(-1) modified the steady-state mean arterial blood pressure-heart rate (MAP-HR) relationship in conscious sheep. At this dose, all three natriuretic peptides are known to enhance the cardiac chemoreflex response to phenylbiguanide (Bezold-Jarisch reflex). Sigmoid MAP-HR relationships were constructed from the steady-state responses to alternating injections of vasopressor (phenylephrine, 1-15 microg kg(-1)) and vasodepressor agents (nitroprusside, 1-15 microg kg(-1)) in the absence and presence of infused ANP, BNP or CNP (tested in random order at least 1 week apart). No parameter of the steady-state baroreflex relationship was significantly altered by infusion of any of the three natriuretic peptides. We conclude that in conscious sheep, normal arterial baroreceptor-HR reflex function prevails in the presence of moderate doses of ANP, BNP or CNP.

Atrial natriuretic peptide (ANP) enhances cardiac vagal baroreflexes in normotensive animals. In spontaneously hypertensive rats (SHRs) this effect of ANP was absent. The reflex actions of ANP were preserved if hypertrophy was completely prevented in SHRs. However even a small amount of cardiac hypertrophy, with no hypertension, in SHRs was accompanied by a loss of the reflex bradycardic actions of ANP. In the present study, we investigated whether pathophysiological cardiac hypertrophy, induced by one-kidney, one-clip renovascular hypertension (1K-1C; n = 6), or physiological cardiac hypertrophy induced by chronic spontaneous, wheel-running exercise training (n = 7), similarly prevented vagal reflex actions of ANP. Cardiac baroreceptor-activated bradycardia was measured during rapid ramp increases ( approximately 5 s) in blood pressure after bolus doses of methoxamine or vehicle in conscious, chronically instrumented rats during infusions of ANP (50 pmol kg(-1) min(-1)). Compared with uninephrectomised control rats (n = 10), rats with 1K-1C had cardiac hypertrophy (approximately 55% increase in left ventricle:body weight (LV:BW) ratio; P < 0.05) and blunted vagal baroreflex gain (-0.93 +/- 0.18 versus-0.50 +/- 0.13 beats min(-1) mmHg(-1); P < 0.05). ANP did not augment baroreflex function in 1K-1C. Compared with their sedentary controls (n = 7), exercise-trained rats with cardiac hypertrophy ( approximately 20% increase LV:BW ratio; P < 0.05) also had blunted ramp baroreflex bradycardia (-1.28 +/- 0.23 versus-0.57 +/- 0.09 beats min(-1) mmHg(-1); P < 0.05). In contrast, ANP more than doubled baroreflex bradycardia in exercise-trained rats (P < 0.05). The aetiology of cardiac hypertrophy therefore influenced whether ANP retained its vagal baroreflex enhancing properties., (Copyright 2004 The Physiological Society)

Wideband enhancement was implemented by detecting visually relevant edge and bar features in an image to produce a bipolar contour map. The addition of these contours to the original image resulted in increased local contrast of these features and an increase in the spatial bandwidth of the image. Testing with static television images revealed that visually impaired patients (n = 35) could distinguish the enhanced images and preferred them over the original images (and degraded images). Most patients preferred a moderate level of wideband enhancement, since they preferred natural-looking images and rejected visible artifacts of the enhancement. Comparison of the enhanced images with the originals revealed that the improvement in the perceived image quality was significant for only 22% of the patients. Possible reasons for the limited increase in perceived image quality are discussed, and improvements are suggested.

Background: Electronic display devices hold the potential to improve access to written material by people with low vision. For those with central field loss, the optimal form of electronic text presentation may vary according to the location of the preferred retinal locus, but this has never been investigated. In this study, we examined the relationship between preferred retinal locus location and reading rate for four electronic display formats (rapid serial visual presentation, horizontal scroll, vertical scroll, and page)., Methods: Short sentences were presented in each format to 35 low-vision (most with central field loss) and 14 age-matched control subjects. Subjects read aloud to determine maximum oral reading rate and read silently to determine preferred silent reading rate., Results: With the exception of page format, maximum oral reading rates were faster than silent preferred reading rates for both groups of subjects. For the low-vision group, there was no significant difference in maximum oral reading rates between the four display formats; and when reading at a preferred silent rate, page format was faster than the other three formats. Though page format was read more quickly, half of the low-vision subjects preferred the horizontal-scroll format. Contrary to our predictions, there was no significant effect of preferred retinal locus location (vertical vs. lateral) on reading rate and no significant interaction between preferred retinal locus location and display format., Conclusions: The differences between maximum oral and preferred silent reading rates and the lack of a relationship between reading rates and preferred display format reinforce the importance of patient preference in the evaluation and selection of a device or display format during rehabilitation.

Two patients presented with long-standing chronic bronchitis and exertional dyspnoea of 5 and 3 months' duration, respectively, and had interlobular septal fibrosis on chest high resolution CT. In the past both had lived in areas in which Strongyloides stercoralis was known to be endemic. Serological tests confirmed the diagnosis of pulmonary strongyloidiasis, and both patients were treated with anti-helminthic medications, including albendazole and ivermectin. Following this there was complete resolution of both symptomatic and radiological manifestations of their disease. An awareness of the possibility of Strongyloides infection presenting with respiratory symptoms in patients exposed to this parasite is important in the management of such patients.

Hess and Dakin reported that normally-sighted subjects using peripheral vision (beyond 10 degrees ) were unable to detect paths of alternating-phase Gabors embedded within randomly positioned Gabors, but could detect same-phase paths. This result led them to propose a "fundamental difference" between central and peripheral visual processing. While we were able to replicate many of their results, our normally-sighted observers could detect alternating-phase paths beyond 10 degrees. We found that path detection decreased monotonically as a function of eccentricity (0 degrees -30 degrees ) for both alternating-phase and same-phase stimuli. As with most visual functions the more difficult path detection condition (alternating-phase) declined slightly faster. The results for the normally-sighted observers could not be explained by poor fixation. Three people with substantial central vision loss (i.e. they can only use peripheral vision) could see both same- and alternating-phase stimuli with eccentric viewing of 13 degrees -17 degrees. Therefore central and peripheral vision appear to use similar visual mechanisms to perform the task, there being no fundamental difference.

Stimulation of cardiomyocyte guanosine 3',5'-cyclic monophosphate (cyclic GMP) via endothelial-derived nitric oxide (NO) is an important mechanism by which bradykinin and ACE inhibitors prevent hypertrophy. Endothelial NO dysfunction and cardiac hypertrophy are morbid features of diabetes not entirely prevented by ACE inhibitors. In cardiomyocyte/endothelial cell cocultures, bradykinin efficacy is abolished by high-glucose-induced endothelial NO dysfunction. We now demonstrate that antihypertrophic actions of natriuretic peptides, which stimulate cyclic GMP independently of NO, are preserved in cardiomyocytes despite high-glucose-induced endothelial dysfunction. Further, streptozotocin-induced diabetes significantly impairs the effectiveness of acute antihypertrophic strategies in isolated rat hearts. In hearts from citrate-treated control rats, angiotensin II-stimulated [(3)H]phenylalanine incorporation and atrial natriuretic peptide and beta-myosin heavy chain mRNA expression were prevented by B-type natriuretic peptide (BNP), bradykinin, the ACE inhibitor ramiprilat, and the neutral endopeptidase inhibitor candoxatrilat. These antihypertrophic effects were accompanied by increased left ventricular cyclic GMP. In age-matched diabetic hearts, the antihypertrophic and cyclic GMP stimulatory actions of bradykinin, ramiprilat, and candoxatrilat were absent. However, the blunting of hypertrophic markers and accompanying increases in cyclic GMP stimulated by BNP were preserved in diabetes. Thus BNP, which increases cyclic GMP independently of NO, is an important approach to prevent growth in the diabetic myocardium, where endothelium-dependent mechanisms are compromised.

1. The objective of the present study was to determine the plasma half-life of B-type natriuretic peptide (BNP) in conscious dogs after intravenous administration and to compare this with its haemodynamic effects. In six chronically instrumented dogs, plasma BNP concentrations were measured under basal conditions, during a constant infusion of canine BNP-32 (10 pmol/kg per min; 25 min) to steady state and at nominated time points up to 75 min after stopping the infusion. Concomitant, continuous measurements of mean arterial blood pressure (MAP), heart rate (HR), central venous pressure (CVP) and mesenteric blood flow (MBF) were obtained. 2. Baseline plasma BNP levels were 15.0 +/- 2.3 fmol/mL and rose approximately 10-fold to 159 +/- 23 fmol/mL after 20-25 min BNP infusion. When the infusion was turned off, plasma BNP levels declined in a biphasic manner, with an initial half-life of 1.57 +/- 0.14 min and a terminal half-life of 301 +/- 85 min. The metabolic clearance rate of BNP was 2.29 +/- 0.34 L/min. 3. The infusion of BNP reduced MAP (approximately 10%), CVP (approximately 65%) and MBF (approximately 25%), whereas haematocrit (approximately 4%) and mesenteric vascular resistance (MVR) increased (approximately 40%; all P < 0.05). Plasma BNP levels returned to baseline by 20 min after BNP infusion had been stopped, whereas none of the haemodynamic variables returned to normal by this time. Mean arterial pressure returned to resting levels within 10-15 min after plasma BNP returned to normal. However, CVP, haematocrit and MBF remained substantially below baseline values for more than 20 min after circulating BNP levels had returned to pre-infusion levels. Of these, only mesenteric vascular changes were returned to baseline within 60 min of plasma BNP levels normalizing. 4. These results demonstrate that the removal of BNP from the canine circulation is rapid, similar to observations made regarding the metabolism of circulating atrial natriuretic peptide in dogs. The half-life of BNP in dogs was shorter than that in rats, sheep or humans. However, the haemodynamic actions of BNP substantially outlasted its plasma half-life. Whether this disparity in plasma level and haemodynamic activity of BNP reflects long-lasting activation of second messenger systems or slow recovery from the hydraulic changes at the capillary level, reflected in the haematocrit and CVP, remains to be answered.

Atrial natriuretic peptide (ANP) potentiates vagal cardiopulmonary reflexes due to chemosensory (Bezold-Jarisch [B-J] reflex) or mechanosensory (ramp baroreflex) activation. The ANP receptor mediating these actions is unknown. We examined the role of particulate guanylyl-cyclase (pGC) receptors in ANP-induced enhancement of cardiopulmonary vagal reflexes. Cardiopulmonary baroreceptor reflex function was assessed by bradycardic responses to ramp blood pressure rises after rapid intravenous methoxamine (100 micro g/kg bolus dose). The B-J reflex was evoked by 3 intravenous doses of serotonin (1 to 10 micro g/kg). In conscious, chronically instrumented rats (n=9), these tests were performed on each animal during randomized infusions of rat ANP (150 ng/kg per minute IV), saline (270 micro L/h IV), the pGC receptor antagonist HS-142-1 (3 mg/kg IV), or combined HS-142-1+ANP treatment. HS-142-1 alone attenuated normal B-J reflex (by 33+/-8%, P<0.05) but not ramp baroreflex responses. As we showed previously, ANP enhanced baroreflex and B-J reflex bradycardia (by approximately 140% and approximately 30%, respectively, P<0.05), compared with saline infusion. These ANP effects were completely blocked by HS-142-1, demonstrating that the cardiopulmonary vagal reflex actions of ANP occurred through pGC natriuretic peptide receptors. Additionally, we have provided evidence for the first time that pGC natriuretic peptide receptors are essential for the full expression of the B-J reflex but not for that of cardiopulmonary vagal baroreflexes. This tonic interaction between pGC natriuretic peptide receptors and cardiopulmonary chemosensitive receptors may be important during pathophysiological activation of B-J reflex, such as with myocardial infarction.

Unlabelled: Atrial natriuretic peptide (ANP) prevents hypertrophy of neonatal cardiomyocytes. However, whether this effect is retained in the adult phenotype or if other members of the natriuretic peptide family exhibit similar antihypertrophic properties, has not been elucidated., Objective: Our objective was to examine whether the natriuretic peptides protect against adult cardiomyocyte hypertrophy in vitro., Methods: Adult rat cardiomyocytes were incubated with angiotensin II (Ang II)+/-ANP, B-type (BNP) or C-type (CNP) natriuretic peptides for determination of [3H]phenylalanine incorporation, c-fos mRNA expression and cyclic GMP. The effects of 8-bromo-cyclic GMP (cyclic GMP analogue), HS-142-1 (particulate guanylyl cyclase inhibitor) and KT5823 (cyclic GMP-dependent protein kinase inhibitor) were also investigated., Results: Ang II-stimulated increases in markers of hypertrophy, [3H]phenylalanine incorporation (to 136+/-3% of control, n=9) and c-fos mRNA expression (4.3+/-1.4-fold, n=5), were completely prevented by each of ANP, BNP or CNP. This protective action was accompanied by increased cardiomyocyte cyclic GMP. Inhibitory actions on [3H]phenylalanine incorporation were mimicked by 8-bromo-cyclic GMP, and were abolished by HS-142-1. KT5823 blocked the response to BNP and CNP, but not to ANP., Conclusion: ANP prevents hypertrophy of adult rat cardiomyocytes. This protective action is shared by BNP and CNP and involves activation of particulate guanylyl cyclase receptors. Antihypertrophic effects of BNP and CNP are mediated through cyclic GMP-dependent protein kinase, but ANP can activate additional pathways independent of cyclic GMP to prevent adult cardiomyocte hypertrophy. These novel findings are of interest particularly since BNP appears to exert antifibrotic rather than antihypertrophic actions in vivo, while CNP is thought to act at least in part via the endothelium.

Repeated measures of wavefront aberrations were taken along the line-of-sight of seven eyes using two instruments: an objective, cross-cylinder aberroscope (OA) and a Shack-Hartmann (SH) aberrometer. Both instruments were implemented on the same optical table to facilitate interleaved measurements on the same eyes under similar experimental conditions. Variability of repeated measures of individual coefficients tended to be much greater for OA data than for SH data. Although Zernike coefficients obtained from a single measurement were generally larger when measured with the OA than with the SH, the averages across five trials were often smaller for the OA. The Zernike coefficients obtained from the two instruments were not significantly correlated. Radial modulation-transfer functions and point-spread functions derived from the two sets of measurements were similar for some subjects, but not all. When average Zernike coefficients were used to determine optical quality, the OA indicated superior optics in some eyes, but the reverse trend was true if Zernike coefficients from individual trials were used. Possible reasons for discrepancies between the OA and SH measurements include difference in sampling density, quality of data images, alignment errors, and temporal fluctuations. Multivariate statistical analysis indicated that the SH aberrometer discriminated between subjects much better than did the objective aberroscope.

Purpose: Because previous studies have reported conflicting evidence, we examined a possible difference in stereoacuity between distance and near, in particular using a random-dot display. We compared distance and near stereoacuities using identical presentation formats at the two distances., Methods: Twelve young adults with low, stable refractive errors and apparently normal binocular vision participated. Stereoacuity was determined with a Mentor B-VAT II using Random Dot E (BVRDE) and Contour Circles (BVC) stereograms presented on a standard monitor (25 x 19.3 cm) at 518 cm (distance-habitual) and a small monitor (2.0 x 1.4 cm) at 40 cm (near-habitual). To examine whether accommodation-convergence influenced stereoacuity, testing at 40 cm was repeated with the addition of +2.50 DS lenses and base-in prisms (near-compensated) that created the same accommodation and convergence demands as for distance-habitual viewing., Results: The two stereotests produced similar findings. Stereoacuity was not significantly different for distance-habitual and near-habitual viewing of the BVRDE (p = 0.43) and BVC (p = 0.79) stereotests. Near-compensated stereoacuity was worse than near-habitual (BVRDE, p = 0.005; BVC, p = 0.004) and distance-habitual (BVRDE, p = 0.05; BVC, p = 0.003) for both stereotests. Because near stereoacuity with yoked prisms (control condition) was the same as without prism (near-habitual), prism-induced optical distortions cannot account for the difference., Conclusions: Stereoacuity was not different at distance and near under normal viewing conditions. The conflict between subject knowledge of target proximity and the optically-induced relaxation of accommodation and convergence, or an inaccurate accommodative-convergence response, might have caused poor near-compensated stereoacuity.

Purpose: To investigate the effects of age-related macular degeneration (ARMD) on mobility performance and to identify the vision determinants of mobility in subjects with ARMD., Methods: Walking speed and the number of obstacle contacts made on a 79-m indoor mobility course were measured in 21 subjects with ARMD and 11 age-matched subjects with normal vision. The mobility measures were transformed to percentage preferred walking speed and contacts score. The vision functions assessed included binocular visual acuity, contrast sensitivity, and visual field., Results: In this study, subjects with ARMD did not walk significantly slower or make significantly more obstacle contacts on the mobility course than the normally sighted subjects of similar age. Between 29% and 35% of the variance in the ARMD mobility performance was accounted for by visual field and contrast sensitivity measures. The most significant predictor of mobility performance scored as percentage preferred walking speed was the size of a binocular central scotoma., Conclusion: As the size of a binocular central scotoma increases, mobility performance decreases.

The antihypertrophic action of angiotensin (Ang)-converting enzyme (ACE) inhibitors in the heart is attributed in part to potentiation of bradykinin. Bradykinin prevents hypertrophy of cultured cardiomyocytes by releasing nitric oxide (NO) from endothelial cells, which increases cardiomyocyte guanosine 3'5'-cyclic monophosphate (cyclic GMP). It is unknown whether cyclic GMP is essential for the action of bradykinin, or whether findings in isolated cardiomyocytes apply in whole hearts, in the presence of other cell types and mechanical/dynamic activity. We now examine the contribution of cyclic GMP to the antihypertrophic action of bradykinin in cardiomyocytes and perfused hearts. In adult rat isolated cardiomyocytes cocultured with bovine aortic endothelial cells, the inhibitory action of bradykinin (10 micromol/L) against Ang II (1 micromol/L)-induced [3H]phenylalanine incorporation was abolished by the soluble guanylyl cyclase inhibitor [1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (10 micromol/L). In Langendorff-perfused rat hearts, Ang II (10 nmol/L)-induced increases in [3H]phenylalanine incorporation and atrial natriuretic peptide mRNA expression were prevented by bradykinin (100 nmol/L), the NO donor sodium nitroprusside (3 micromol/L), and the ACE inhibitor ramiprilat (100 nmol/L). The acute antihypertrophic action of bradykinin was accompanied by increased left ventricular cyclic GMP, and the ramiprilat effect was attenuated by HOE 140 (1 micromol/L, a B2-kinin receptor antagonist) or [1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (100 nmol/L). In conclusion, bradykinin exerts a direct inhibitory action against the acute hypertrophic response to Ang II in rat isolated hearts, and elevation of cardiomyocyte cyclic GMP may be an important antihypertrophic mechanism used by bradykinin and ramiprilat in the heart.

Objective: Since the pathophysiology of natriuretic peptides in chronic heart failure (HF) is not uniform, we hypothesized that atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) may also have differential effects in acute HF. Our aim was to compare the haemodynamic actions of ANP with BNP, using a classical vasodilator as the control, in greyhound dogs with acute pacing-induced HF., Design and Methods: The right ventricles of eight anaesthetized dogs were paced (193 +/- 4 bpm) until pulmonary capillary pressure (PCP) increased to approximately 15 mmHg. In each animal, according to a randomized within-animal design, haemodynamic responses to equimolar (10 pmol/kg per min) infusions of ANP and BNP were compared with those to sodium nitroprusside (SNP)., Results: Acute pacing alone increased PCP from 6.6 +/- 0.7 to 15.7 +/- 0.3 mmHg, right atrial pressure (RAP) from 1.9 +/- 0.5 to 4.0 +/- 0.6 mmHg, and systemic vascular resistance (SVR) from 1706 +/- 110 to 2179 +/- 106 dyne s/cm5, and reduced cardiac output (CO) from 4.1 +/- 0.4 to 2.5 +/- 0.2 l/min and arterial pressure from 86.1 +/- 2.4 to 74.5 +/- 2.1 mmHg (all P < 0.01). BNP and SNP improved haemodynamics similarly (CO +13 +/- 3% and +9 +/- 5%; PCP -12 +/- 2% and -12 +/- 2%; RAP -28 +/- 9% and -34 +/- 6%, SVR -15 +/- 3% and -11 +/- 3%, all P < 0.01, except CO with SNP, not significant), but effects of BNP on preload outlasted those of SNP. By contrast, ANP did not improve the haemodynamics. Haematocrit was significantly higher during BNP infusion than with ANP (P < 0.05) or with SNP (P < 0.001)., Conclusions: The haemodynamic responses to exogenous BNP and ANP in acute heart failure were strikingly different. Whereas ANP actions were blunted, BNP response was preserved. Hypothetically, the presence of a putative BNP receptor may explain this finding.

Previous findings indicate that atrial natriuretic peptide (ANP) enhances the reflex bradycardia arising from stimulation of cardiac mechanoreceptors and chemoreceptors, but not that from arterial baroreceptors. The present study tests this proposal by examining the effect of ANP on these reflexes in six chronically sinoaortic-denervated (SAD), and eight sham-operated (sham), conscious rats. Arterial baroreceptor-heart rate (HR) reflex function was examined by constructing full-range steady-state blood pressure (BP)-HR curves using alternating doses of pressor (methoxamine, 2-100 microg/kg) and depressor (nitroprusside, 1-50 microg/kg) agents. Nonarterial baroreceptor reflex function was assessed by the 'ramp' bradycardic response to the rapid BP rise after i.v. methoxamine (100 microg/kg bolus dose). The cardiopulmonary chemoreflex was evoked by i.v. injections of serotonin (1-20 microg/kg). These three tests were performed on each rat during infusions, in random order, of rat ANP (150 ng/kg/min i.v.) and saline vehicle. The ability of ANP to significantly enhance ramp reflex bradycardia was not diminished in SAD compared with sham rats (+54 +/- 12% vs. +42 +/- 15%, respectively). ANP also significantly enhanced cardiopulmonary chemoreflex bradycardia in both groups (+60 +/- 15% in SAD, +40 +/- 8% in sham). Neither the normal steady-state BP-HR response in sham rats nor the small residual response in SAD rats was enhanced by ANP (-1 +/- 7% in sham, -11 +/- 8% in SAD). We conclude that ANP enhances reflex bradycardias of nonarterial, probably cardiac mechanoreceptor, origin.

Usually a high-contrast, co-local mask increases contrast threshold (inhibition). Interestingly, a laterally displaced mask (flanker) can facilitate contrast detection (Vision Research 33 (1993) 993; 34 (1994) 73). When spatial scaling of these flanker effects was implied, stimulus bandwidth was confounded with spatial frequency (lambda(-1)). Under conditions where at lower spatial frequencies, the size (standard deviation, sigma) of the Gabor patch was smaller (sigma

Optimal delivery of healthcare requires consideration of various costs. A foldable intraocular lens (IOL) is more expensive than an equivalent rigid IOL. However, surgical and post-operative costs may make a foldable IOL economically preferable. We compared the economic costs of cataract surgery plus implantation of a foldable IOL with implantation of a rigid IOL. Prospective audit of the clinical records of 82 pseudophakes; 39 implanted with a rigid IOL and 43 implanted with a foldable IOL by one surgeon. Average follow-up periods were 25 +/- 7 months and 23 +/- 5 months respectively. There was no difference between the two groups for the follow-up period (P = 0.55), number of post-operative complications (P = 0.25) or cost of post-operative visits (P = 0.83). The cost of single-use theatre equipment was greater for the rigid-IOL group (P= 0.0001). The total identified cost per patient was greater for the foldable-IOL group (P = 0.0001). Despite possible technical advantages, implantation of the foldable IOL did not provide an economic benefit, either in the initial cost or in the costs of post-operative care. Over the 2-year period, implanting with the rigid IOL cost, on average, Pound Sterling57 less per patient. Despite this economic difference, a cost-benefit analysis is required, since other factors may be more important.

Purpose: Reading rate has been the main performance measure in studies that have compared reading with large print and optical magnifiers; eye movement characteristics have not been considered. We compared both eye movement characteristics and reading rates for subjects with macular disease reading without and with a range of low-vision devices., Methods: Silent reading rate and eye movement characteristics for text passages at critical print size of 21 subjects aged 14 to 88 years with macular disease were measured with and without their preferred low-vision device. Saccadic frequency was determined from a sequencing task comprising five letters each separated by 5 degrees. Eye movements were recorded using an infrared limbal reflection system., Results: There were no significant differences in reading rate, fixation durations, saccade numbers per word, or percent retrace time when using a low-vision device compared with reading without a low-vision device. The percentage of regressions was, however, lower with the low-vision device. Saccadic frequency in the sequencing task was predictive of reading performance with and without a low-vision device., Conclusions: When reading at critical print size, in terms of reading rate or saccades per word, there was no advantage to using large print over an optical low-vision device.

Objectives: We sought to assess the effects of brain natriuretic peptide (BNP) on systemic and regional sympathetic nervous activity (SNA) in both patients with congestive heart failure (CHF) and healthy control subjects., Background: Although the response of SNA to atrial natriuretic peptide (ANP) has been well documented, the response of SNA to BNP is largely unknown., Methods: We assessed cardiac and whole-body SNA using the norepinephrine (NE) tracer dilution method before and after infusion of two doses of BNP (3 and 15 ng/kg body weight per min) in 11 patients with stable CHF (ejection fraction 24 +/- 2%) and 12 age-matched healthy control subjects. In addition, renal SNA and hemodynamic variables were assessed at baseline and after the higher BNP dose., Results: Low dose BNP did not change blood pressure or whole-body NE spillover, but reduced cardiac NE spillover in both groups by 32 +/- 13 pmol/min (p < 0.05). In both groups, high dose BNP reduced pulmonary capillary pressure by 5 +/- 1 mm Hg (p < 0.001) and mean arterial pressure by 6 +/- 3 mm Hg (p < 0.05), without a concomitant increase in whole-body NE spillover; however, cardiac NE spillover returned to baseline levels. Renal NE spillover remained virtually unchanged in healthy control subjects (501 +/- 120 to 564 +/- 115 pmol/min), but was reduced in patients with CHF (976 +/- 133 to 656 +/- 127 pmol/min, p < 0.01)., Conclusions: Our results demonstrate a sympathoinhibitory effect of BNP. Cardiac sympathetic inhibition was observed at BNP concentrations within the physiologic range, whereas high dose BNP, when arterial and filling pressures fell and reflex sympathetic stimulation was expected, systemic and cardiac SNA equated to baseline values. There was inhibition of renal SNA in patients with CHF, but not in healthy control subjects. Whether this effect is specific to BNP or related to reduced filling pressure remains to be determined.

We demonstrated previously that atrial natriuretic peptide (ANP) enhances reflex bradycardia to intravenous serotonin [5-hydroxytryptamine (5-HT)] (von Bezold-Jarisch reflex) in rats. To determine whether 1) ANP affects this cardiopulmonary vagal reflex in another species and 2) B-type (BNP) and C-type (CNP) natriuretic peptides share with ANP the ability to modulate this reflex, we used intravenous phenylbiguanide (PBG), a 5-HT(3) agonist, as the stimulus to evoke a von Bezold-Jarisch reflex (dose-related, reproducible bradycardia) in conscious adult sheep (n = 5). Three doses of PBG (13 +/- 3, 20 +/- 3, and 31 +/- 4 microg/kg) injected into the jugular vein caused reflex cardiac slowing of -7 +/- 1, -15 +/- 2, and -36 +/- 3 beats/min, respectively, under control conditions. These doses of PBG were repeated during infusions of ANP, BNP, or CNP (10 pmol. kg(-1). min(-1) iv), or vehicle (normal saline). Each of the natriuretic peptides significantly (P < 0.05) enhanced the sensitivity of bradycardic responses to PBG by 94 +/- 8% (ANP), 142 +/- 55% (BNP), and 61 +/- 16% (CNP). Thus not only did ANP sensitize cardiopulmonary chemoreceptor activation in a species with resting heart rate close to that in humans, but BNP and CNP also enhanced von Bezold-Jarisch reflex activity in conscious sheep.

To distinguish normal from pathological corneal fluorescein staining requires knowledge of background levels of staining among otherwise healthy individuals. Corneal staining of 102 non-contact lens wearing subjects was assessed using a photographic grading scale that uses a generic (0 to 4) scale to score corneal staining. Some degree of corneal staining was found on 79% of the corneas. Low inter-observer variability suggests that the corneal staining grading scale can be used successfully with decimal rather than integer scale increments.

Purpose: To categorize the appearance of the normal upper palpebral conjunctiva using a grading scale and to investigate interobserver agreement with a grading scale modified to include decimal increments., Methods: Upper palpebral conjunctival appearance of 96 non-contact lens wearing subjects aged 18 to 75 years was assessed using a photographic grading scale that has a generic (zero to four) scale to score redness and roughness of the palpebral conjunctiva., Results: Median redness and roughness was about 1.25 units. About 5% of subjects had redness or roughness >2.0 units. Interobserver agreement improved during the study. By the end of the study, the standard deviation of the discrepancy scores was 0.12 to 0.19 units., Conclusions: Upper palpebral conjunctival redness or roughness >2.0 units are unusual. The grading scale can be used successfully with decimal rather than integer scale increments. For experienced clinicians, a change in grade of > or =0.5 units may be significant.