Visual function assessment in simulated real-life situations in patients with age-related macular degeneration compared to normal subjects.

Purpose: To evaluate visual function variations in eyes with age-related macular degeneration (AMD) compared to normal eyes under different light/contrast conditions using a time-dependent visual acuity testing instrument, the Central Vision Analyzer (CVA).

Methods: Overall, 37 AMD eyes and 35 normal eyes were consecutively tested with the CVA after assessing best-corrected visual acuity (BCVA) using ETDRS charts. The CVA established visual thresholds for three mesopic environments (M1 (high contrast), M2 (medium contrast), and M3 (low contrast)) and three backlight-glare environments (G1 (high contrast, equivalent to ETDRS), G2 (medium contrast), and G3 (low contrast)) under timed conditions.

Screening athletes with Down syndrome for ocular disease.

Background: Persons with Down syndrome are well known to have a high prevalence of vision and eye health problems, many of which are undetected or untreated primarily because of infrequent ocular examinations. Public screening programs, directed toward the pediatric population, have become more popular and commonly use letter or symbol charts. This study compares 2 vision screening methods, the Lea Symbol chart and a newly developed interactive computer program, the Vimetrics Central Vision Analyzer (CVA), in their ability to identify ocular disease in the Down syndrome population.

Contribution of vasoconstriction to the origin of atherosclerosis: a conceptual study.

Research during the past century has clearly shown that endothelial injury (EI) and/or endothelial dysfunction (ED) are among the major events determining the onset of atherosclerosis. Included in the events that may elicit endothelial damage, vasoconstriction (VC) has received relatively little attention. This conceptual review attempts to show that in elastic and conduit arteries, VC is not only capable of producing EI/ED, but is also closely associated with many recognized proatherogenic stimuli.

Vasospasm, vascular injury, and atherogenesis: a perspective.

It is generally believed that injury of the vessel wall is an important condition for the development of atherosclerosis. The nature of this injury and its relationship to lesion origin, however, are not clearly understood. Based on early work by the author and a selective review of the literature, evidence is presented to show how a common cardiovascular event, vasospasm, may be one of the factors responsible for this tissue damage, because it produces a substantial arteriopathy in the very vessel in which it occurs.

Increased serum mitogenic activity for arterial smooth muscle cells associated with relaxation and low educational level in human subjects with high but not low hostility traits: implications for atherogenesis.

Proliferation of arterial smooth muscle cells (aSMC) is a key component of atherogenesis. A sample of 225 volunteers, aged 21-65 years, was exposed to "frustration," "harassment," or "relaxation," after completing the 50-item Hostility subscale of the Minnesota Multiphasic Personality Inventory (MMPI). Whole blood was measured before and after exposure for platelet-derived growth factor (PDGF), and sera were evaluated for total and HDL cholesterol concentrations and PDGF-independent mitogenic activity (SMA).

Control of human vascular smooth muscle cell proliferation by sera derived from 'experimentally stressed' individuals.

Recently we reported that individuals with high scores in standardized hostility evaluation tests, when placed in a environment, may have an association with increases in a blood-borne mitogenic substance(s) for arterial smooth muscle cells. To further investigate the molecular basis for such an association, PDS [plasma derived serum with platelet derived growth factor (PDGF) removed] from individuals showing the greatest differential pre/post-stress mitogenic activity, were tested for ability to modulate changes in the steady state of the c-myc mRNA in cultured VSMC (vascular smooth muscle cells) by Northern blot analysis. Post-stress PDS resulted in a significant increase in c-myc mRNA, when compared with pre-stress PDS of the same individual.

The anti-proliferative effects of nicotinamide and 3-aminobenzamide on human smooth muscle cells in vitro.

The proliferation of cultured human arterial smooth muscle cells (HASMC) was suppressed by nicotinamide and its analogue, 3-aminobenzamide, in a concentration-dependent manner, based on cell count and [3H]thymidine incorporation into DNA. The addition of 10 and 15 mM nicotinamide, or 6 mM 3-aminobenzamide, to HASMC, for 96 h, resulted in a 19.3%, 44% and 41.

Growth retardation in senescent arterial smooth muscle cells and its reversal following brain stimulation: implications for atherogenesis.

Advancing age and psychosocial stress are each associated with a rising incidence of atherosclerosis. In this investigation we attempted to answer the question of whether they are independent of each other or not. Since a key feature of atherosclerosis is the proliferation of arterial smooth muscle cells (ASMC), we transplanted aortic tissue from aged rats, half of which had received hypothalamic stimulation, as a model for stress, to growth supporting medium, immediately after stimulation and observed their growth behavior for a period of 4 months.

Therapeutic benefit of captopril in salt-loaded stroke-prone spontaneously hypertensive rats is independent of hypotensive effect.

In the present study we examined whether the angiotensin I converting enzyme inhibitor, captopril, would protect stroke-prone spontaneously hypertensive rats (SHRSP) from stroke and renal pathology over a 26-week period. In the control group of six untreated SHRSP fed Stroke-Prone Rodent Diet and 1% NaCl drinking solution, all animals developed severe hypertension and stroke by 16.1 weeks of age.

Age differences in the proliferative response of cultured arterial smooth muscle cells induced by sera of hypothalamically-stimulated rats.

In an earlier report, it was shown that arterial smooth muscle cells (ASMC) cultured from normal rat aorta, proliferated in response to homologous sera from young rats which had received hypothalamic stimulation (HS), in contrast to the effect of sera from non-stimulated age-matched controls (sham-operated). In the present study, this proliferative response was compared in young and old rats. Isolated target cells were subcultured from primary explants of aortic tissue obtained from young, male, Fischer 344 rats, which were electrode-implanted in the hypothalamus but not stimulated.

The central nervous system and atherogenesis: role of the arterial smooth muscle cell.

Within the last 2-3 decades neuropsychological factors have assumed a role of importance in atherogenesis implicating a contribution from the CNS to the development of arterial lesions. Despite extensive documentation in clinical studies, little work has been performed with experimental animals which could elucidate underlying mechanisms. Employing hypothalamic stimulation (HS) to model the role of the CNS, experiments in the author's laboratory have shown that atherosclerotic lesions develop in time.

Effects of alcohol on isoproterenol-induced ventricular fibrillation in adult rats.

To determine whether the pattern of alcohol consumption, intake, and withdrawal modulates the incidence of malignant ventricular arrhythmias and sudden cardiac death due to beta-adrenergic stimulation in a species susceptible to administration of isoproterenol alone, a regimen was formulated in which both continuous and interrupted alcohol ingestion was obtained. After alcohol treatment of fully mature, adult rats for 7 weeks, a single subcutaneous injection of 150 micrograms/kg of isoproterenol was given to control (non-alcohol-treated), alcoholic (continuous consumption), and alcohol withdrawal (interrupted) rats. The incidences of malignant ventricular arrhythmias and related deaths were compared.

The central nervous system and atherogenesis: endothelial injury.

Although it has been widely acknowledged that endothelial injury is an important contributing factor to the pathogenesis of atherosclerosis, and may even represent an initiating event, morphologic documentation of its occurrence both in humans and animals has been difficult to obtain. However, electrical stimulation of the lateral hypothalamus in conscious, unrestrained animals on normal diets induces severe endothelial damage with cell loss and denudation in both aortas and coronary arteries. Continued stimulation results in intimal lesions with features of atherosclerotic plaques.

Spasm of small coronary arteries and ischemic myocardial injury induced by hypothalamic stimulation in the rat.

Electrical stimulation of the lateral hypothalamus resulted in electrocardiographic evidence of acute myocardial ischemia in 35% of normal adult rats under anesthesia. Mean arterial blood pressure was also elevated. Study of vascular corrosion casts disclosed that spasm of smaller branches of the coronary circulation, rather than the major epicardial arteries, was the main cause of the ischemic response.

Coronary artery spasm: involvement of small intramyocardial branches.

A study was conducted to determine if the small (resistance) vessels of the coronary circulation could undergo spasm comparable to that of the major conductance (epicardial) arteries which in the rat measure 275-300 micron in diameter. This information may be relevant to the growing evidence of ischemic myocardial disease without significant coronary atherosclerosis or even spasm of the larger vessels. Vascular corrosion casts of the coronary circulation were prepared in the rat 20 min after intravenous injection of arginine vasopressin, a powerful coronary constrictor substance, under continuous electrocardiographic monitoring.

Ventricular fibrillation and the Brattleboro rat.

Despite considerable evidence from both clinical and animal experiments, the role of beta-adrenergic stimulation in the development of life-threatening cardiac arrhythmias is not well understood. Recent studies indicate that the posterior pituitary hormone, arginine vasopressin, may have a modulatory effect on cardiovascular sympathetic tone, especially with respect to blood pressure and heart rate. Employing the homozygous Brattleboro rat, an animal genetically deficient in the synthesis of arginine vasopressin, the following report offers evidence that the neuropeptide may also act on central pathways to suppress arrhythmogenic activity elicited by beta-adrenoceptor stimulation.

Proliferation of arterial smooth muscle cells incubated in serum from brain-stimulated rats.

Platelet deficient serum prepared from rats subjected to acute electrical stimulation of the lateral hypothalamus demonstrated mitogenic activity when added to incubating media supporting growth of homologous arterial smooth muscle cells in vitro. This activity did not appear to be related to the presence of platelet-derived growth factor, hyperlipidemic lipoproteins or increased amounts of insulin. Plasma arginine vasopressin concentration was elevated in these animals, but further investigation is required to determine if this elevation is causally related.

Coronary artery spasm in the rat induced by hypothalamic stimulation.

Anesthetized rats were sterotaxically implanted with electrodes and electrically stimulated in the lateral hypothalamus. During elevation of the S-T segment on simultaneous precordial electrocardiograms, the heart was perfused with glutaraldehyde-paraformaldehyde fixative and the major coronary arteries prepared for morphometry of luminal dimensions. A similar procedure was performed in a second group receiving intravenous arginine vasopressin (AVP) in place of hypothalamic stimulation.

Endothelial morphology and plasma total and high density lipoprotein cholesterol changes in hypothalamically stimulated squirrel monkeys fed a modified atherogenic diet.

Experimental animals fed atherogenic diets show endothelial damage, impairment of endothelial regeneration and plasma lipid changes characterized by elevation of LDL and decrease of HDL cholesterol concentrations. Previous studies in this laboratory disclosed that chronic electrical stimulation of the lateral hypothalamus was associated with electron-microscopic evidence of endothelial injury in rats and squirrel monkeys maintained on basal (low fat/cholesterol-free) diets. In the present investigation squirrel monkeys fed similar diets supplemented with "modest" amounts of caloric fat and cholesterol were subjected to chronic lateral hypothalamic stimulation for periods as long as 20 months with the expectation that endothelial injury would be greater than in the absence of the supplements.

Effect of hypothalamic stimulation on the endothelial morphology of the aorta in the conscious squirrel monkey.

The role of neurogenic factors in the development of atherosclerosis has not previously been studied in detail. In recent years evidence has accumulated to implicate endothelial injury as a primary stimulus for the proliferation of myo-intimal cells resulting in the formation of the early morphologic lesion. In the present investigation, the effect on aortic endothelial morphology of repetitive electrical stimulation of the lateral hypothalamus in the conscious, unrestrained squirrel monkey, maintained on a cholesterol-free low-fat diet, has been studied.

Relationship of small and large coronary artery disease to myocardial ischemia.

To determine the relative roles of narrowing of the small intramyocardial arteries and of the large extramural coronary arteries in the development of ischemic myocardial lesions, hearts were obtained at the autopsies of 105 adults for morphologic study. Subendocardial ischemic lesions frequently were associated with narrowing of the small arteries even in the absence of major coronary artery stenosis. However, transmural ischemic lesions occurred almost always with large coronary artery disease, either alone or in combination with narrowing of the small arteries.

A minimum component AM transmitter to monitor electronic brain stimulation.

Construction of a light weight AM transmitter which can be used to monitor implanted electronic brain stimulators is described. The unit can operate continuously for 40 hours on a single battery and can easily be carried by a small laboratory animal. The range of the unit is limited to approximately 1 meter and the transmitted signal can be detected by a standard AM broadcast band receiver.