Biomedical subjects

S M Podos

Publications and source records attributed to S M Podos.

At least 91 records · Page 5Linked to original sources

PubMed1986

Flash and pattern electroretinograms in normal and laser-induced glaucomatous primate eyes.

Experimental glaucoma was produced in one eye of five cynomolgus monkeys with the argon laser delivering 100-200 50-mu spots at 1200-1500 mW power and 0.5 sec to 360 degrees of the mid-trabecular meshwork. Monocular electroretinograms (ERGs) were recorded prior to and 2, 3, and 4 mo following the laser treatment. In the laser-treated (glaucoma) eyes, normal flash ERGs were observed using 1-Hz stimulation; however, pattern ERGs (PERGs) elicited using steady-state counterphase modulation of a 0.51 cpd square wave grating showed statistically significant reductions of amplitude. Only small reductions of PERG amplitude were seen with a 1.25 cpd grating. In three animals, abnormalities of the PERG occurred prior to clinically significant cupping of the optic nervehead. Moreover, reductions of PERG amplitude were progressive and associated with the magnitude of cupping of the optic nervehead and elevation of intraocular pressure. PERG amplitude did not change following acute reductions in intraocular pressure in the glaucoma eyes. Several control experiments were conducted to insure that results were not due to alterations in pupil size, refractive state, or accommodation in the glaucoma eyes. The authors believe they now have a monkey model for the electrophysiologic study of glaucoma.

Animals↗

PubMed1985

Inhibition of the epinephrine-induced reduction of intraocular pressure by systemic indomethacin in humans.

In a prospective, randomized, double-masked study, 2% epinephrine applied topically twice each day for two weeks to the eyes of patients with glaucoma or ocular hypertension caused an 8.1 +/- 1.4-mm Hg (mean +/- S.E.M.) reduction of intraocular pressure in placebo-treated patients, but only a 1.9 +/- 0.6-mm Hg decrease in patients treated with 25 mg of orally administered indomethacin four times each day (P less than .0005). Systemic treatment with indomethacin for one week did not significantly increase intraocular pressure by itself (baseline, 19.7 +/- 0.6 mm Hg, vs 20.1 +/- 1.4 mm Hg after indomethacin treatment). When indomethacin treatment was discontinued in those patients receiving topical epinephrine, there was a further significant (P less than .05) reduction in intraocular pressure compared with the placebo-treated group. Since the ocular hypotensive effect of topically applied epinephrine is inhibited by indomethacin, a cyclo-oxygenase inhibitor, these results suggest that this reduction of intraocular pressure is at least partially mediated by the endogenous production of prostaglandins, or other cyclo-oxygenase products, and that the intraocular pressure of glaucoma patients undergoing epinephrine therapy may increase when systemic cyclo-oxygenase inhibitors such as indomethacin or aspirin are taken.

Administration, Oral↗

PubMed1985

Comparison of standard and computerized tonography instruments on human eyes.

We compared the outflow facility coefficient results after indentation tonography obtained with a standard tonography unit and with a new computerized tonography machine. Goldmann applanation tonometry was followed by standard tonography on one eye and computerized tonography on the other. After a one-hour equilibration period, tonometry was repeated and followed by tonography with the testing units used on the opposite eyes. In nine of 60 eyes the results were discarded because of poor tracings or high error. Results of initial indentation intraocular pressure measured by the two units were not statistically different from those measured by Goldmann applanation tonometry. Mean outflow facilities determined by the standard unit and by the computerized machine with the average scleral rigidity program showed no statistically significant difference by the paired t-test.

Aqueous Humor↗

PubMed1985

Alpha-adrenergic antagonists: correlation of the effect on intraocular pressure and on alpha 2-adrenergic receptor binding specificity in the rabbit eye.

Six alpha-adrenergic antagonists, which have a range of selectivities for alpha 1- and alpha 2-adrenoreceptor subtypes, were compared with respect to their ability to reduce intraocular pressure (IOP) after topical application to the rabbit eye, and their affinity and selectivity for alpha 2-adrenoreceptors, as determined by binding to membranes prepared from rabbit iris-ciliary body. A routine assay for alpha 2-adrenoreceptors using [3H]-rauwolscine was developed for this purpose. ICB contained 200-300 fmol (mg protein)-1 alpha 2-adrenoreceptors which represents approximately two-thirds of the total number of alpha-adrenoreceptor sites present in this tissue. All six antagonists bound at alpha 2-adrenergic receptor sites in an apparently simple competitive manner. The Kd for three of the drugs was about 10 nM (rauwolscine, yohimbine, WB-4101) and the Kd for the other three was greater than 3500 nM (prazosin, corynanthine, thymoxamine). However, all six antagonists were effective ocular hypotensive agents when given topically in a 50 microliter dose of 1% (w/v) concentration. The ability of alpha-adrenergic antagonists to lower IOP in the rabbit did not correlate with a single alpha-receptor subtype and appears to involve at least two separate mechanisms, one mediated by alpha 2-adrenergic receptors and one mediated by alpha 1-adrenergic receptors.

Adrenergic alpha-Antagonists↗

PubMed1985

The effect of corynanthine on intraocular pressure in clinical trials.

A single drop, dose-response, double-masked study of the effect corynanthine, a selective alpha 1 adrenergic antagonist, on intraocular pressure (IOP) was carried out in 10 symmetrically ocular hypertensive patients. Corynanthine 1% had no significant pressure lowering effect. Topical application of a 2% solution significantly (P less than 0.05) reduced IOP for at least eight hours; at five hours, mean IOP (+/- SEM) was 20.6 +/- 2.0 mmHg and 26.0 +/- 4.9 mmHg, comparing treated and control eyes, respectively. The 5% solution caused a significant (P less than 0.05) bilateral reduction in IOP, comparing treated and control eyes to baseline IOP respectively. Two percent corynanthine applied topically two or three times daily for one, two, or three weeks to seven patients with symmetrical ocular hypertension did not reduce IOP. Alpha adrenergic antagonists may have a role in the treatment of glaucoma.

Adrenergic alpha-Antagonists↗

PubMed1985

Retinal acuity evaluation with the potential acuity meter in glaucoma patients.

The potential acuity meter (PAM) is designed to evaluate retinal acuity in the presence of media opacities. We looked at patients with glaucoma but with clear media, and compared best corrected visual acuity with PAM results to see if they produced comparable results. Sixty eyes in 38 glaucoma patients and 20 eyes in 10 normal ocular patients were evaluated. Our results indicate that PAM visual acuity is a reliable indicator of Snellen visual acuity in normal eyes, in eyes with mild to moderate glaucomatous damage, and when PAM visual acuity measurements were better than 20/60. However, when visual field loss is severe and when PAM visual acuity readings were worse than 20/60, the correspondence between these and Snellen visual acuity was erratic. Poor PAM results will not correlate with postoperative visual acuity in patients with advanced glaucoma and cataracts.

Glaucoma↗

PubMed1985

The optically determined corneal and anterior chamber volumes of the cynomolgus monkey.

We described an optical method of measuring corneal volume and employed the optical method of Johnson et al. for measuring the volume of the anterior chamber in cynomolgus monkey. In 12 normal monkey eyes, the corneal volume was found to be 40.4 +/- 2.3 microliter (mean +/- S.E.) and the anterior chamber volume was 101.8 +/- 4.2 microliter (mean +/- S.E.).

Animals↗

PubMed1985

Pharmacological testing in the laser-induced monkey glaucoma model.

Glaucoma was induced in cynomolgus monkeys by photocoagulating the trabecular meshwork with the argon laser. Repeat treatments were often necessary and wide intraocular pressure fluctuations were characteristic. Baseline intraocular pressure was measured with a calibrated pneumatonometer hourly for six hours. On a succeeding day a baseline measurement was made, 50 microliter of the drug to be tested applied, and six hourly measurements of intraocular pressure repeated. The effects on intraocular pressure of timolol, epinephrine, pilocarpine, vanadate, prostaglandin F2 alpha (PGF2 alpha), forskolin, and corynanthine were tested in at least eight eyes. Significant (p less than 0.05) reductions of intraocular pressure were produced by 0.5% timolol, 2% epinephrine, 4% pilocarpine, 1% vanadate, 500 micrograms of PGF2 alpha and 1% forskolin. Five per cent corynanthine produced no significant lowering of intraocular pressure. Tonography revealed an increased outflow facility associated with the reduction of intraocular pressure 2 hours after the administration of 4% pilocarpine. This glaucoma animal model may be useful in investigating agents that lower intraocular pressure by a variety of mechanisms.

Administration, Topical↗

PubMed1985

Ocular hypotension in the rabbit. Receptor mechanisms of pirbuterol and nylidrin.

Pirbuterol and nylidrin, both purported sympathomimetic amines, reduced intraocular pressure (IOP) when given topically (50 microliter, 0.1%) to albino rabbits. Pirbuterol increased the cyclic-AMP concentration in aqueous humor by a factor of 3.25, while nylidrin had no effect on aqueous cyclic-AMP nor on adenylate cyclase activity of iris-ciliary body membranes assayed in vitro. Studies of the receptor affinity of pirbuterol, timolol and nylidrin were carried out on iris-ciliary body membranes by competition binding with radioactive ligands. Four ligands were used that appear to label separate subpopulations of adrenergic receptors; dihydroalprenolol (beta-receptors), WB-4101 (alpha 1-receptors) prazosin (alpha 1-receptor subpopulation) and yohimbine (alpha 2-receptors). Pirbuterol and timolol showed exclusive selectivity for beta-receptors with high affinities (Kd 12.6 and 0.48 nM, respectively) compared with other adrenergic receptor populations in iris-ciliary body. Nylidrin had high affinities for beta-receptors (Kd 22 nM) and for the subpopulation of alpha 1-receptors labelled by prazosin (Kd 6.5 nM), but showed 100-fold lower affinity and complex binding characteristics to the two other classes of alpha-adrenergic receptor sites labelled by WB-4101 and yohimbine, respectively. The results show that pirbuterol and timolol are highly beta-receptor selective and that hypotensive responses to these drugs are not mediated by the other classes of alpha-adrenergic receptor determined in this study. However, the hypotensive response to nylidrin may be related to its prazosin-like (alpha 1-receptor) antagonist properties with additional activity at beta-receptors.

Adenylyl Cyclases↗

PubMed1984

Laser trabeculoplasty. A prospective study of treatment variables.

Forty-five phakic eyes with open-angle glaucoma and uncontrolled intraocular pressure underwent laser trabeculoplasty. Each eye was assigned randomly to one of three treatment groups: group 1, 100 spots over 360 degrees; group 2, 50 spots over 180 degrees; or group 3, 50 spots over 360 degrees. A 50-micron spot was aimed at the anterior meshwork; power and time were varied to achieve a blanch. Forty-four eyes were followed up for at least four weeks without further intervention. The mean IOP before therapy and the initial IOP elevation were similar in all groups. After four weeks, the mean IOP reductions in 15 eyes in group 1, 15 eyes in group 2, and 14 eyes in group 3 were not significantly different. However, significantly more eyes in group 1 demonstrated a greater than 12 mm Hg reduction in IOP than eyes in the other groups. Group 2 tended to have the fewest eyes with reduced medications.

Aphakia↗

PubMed1984

Corynanthine and aqueous humor dynamics in rabbits and monkeys.

The effects of corynanthine tartrate, a selective alpha 1-adrenergic receptor antagonist, were studied on intraocular pressure by pneumatonometry, outflow facility by tonography, and aqueous humor flow by fluorophotometry in laboratory animals. Unilateral topical administration of 5% corynanthine significantly lowered mean IOP (+/- SEM) in rabbits for at least six hours, in ten awake monkeys for six hours, and in ten monkeys anesthetized with ketamine for four hours. The maximum effect in awake monkeys occurred two hours after drug administration, from 15.8 +/- 0.5 mm Hg to 12.7 +/- 0.5 mm Hg, with no substantial change in control eyes. No change in outflow facility was demonstrated in 11 monkeys two hours after 5% corynanthine administration. Aqueous humor flow rates did not change in 12 monkeys up to three hours after drug administration. Corynanthine may act by increasing uveoscleral outflow.

Adrenergic alpha-Antagonists↗

PubMed1984

Transepithelial electrical measurements on the isolated rabbit iris-ciliary body.

Transmural electrical properties of the isolated rabbit iris-ciliary body (I-CB) were measured in Ussing-Zerahn-type chambers. Control p.d. across the preparation was -1.2 +/- 0.1 mV, with the ciliary process (aqueous)-side consistently negative with respect to the ciliary body (blood)-side and the short-circuit current (SCC) was 7.9 +/- 0.6 microA cm-2. Bilateral bathing solution substitutions demonstrated absolute requirements for the presence of Na+, K+ and HCO3-for the maintenance of the p.d. Addition of 5 X 10(-5) M ouabain to the aqueous-side chamber increased the p.d. and SCC initially, with a subsequent decline to zero. Only a declining phase was observed when ouabain was added to the blood-side. Ouabain inhibited oxygen consumption by 28% in Tyrode's solution. Respiratory rate was also approximately 28% lower in Na+-free and K+-free Tyrode's solution and ouabain had no additional inhibitory effect in either of these two solutions. Thus the biphasic effect of ouabain on the electrical parameters cannot be explained by a toxic effect but rather as a selective inhibition of the Na+-, K+-pump. Our results indicate that Na+-, K+-ATPase activity and the presence of HCO3- are required for active ion transport in this preparation.

Action Potentials↗

PubMed1984

Congenital ectropion uveae with glaucoma.

Congenital ectropion uveae (CEU) is a rare, nonprogressive anomaly characterized by the presence of iris pigment epithelium on the anterior surface of the iris stroma, often associated with neurofibromatosis and occasionally with other ocular anomalies. We present eight patients with unilateral CEU. Seven patients had glaucoma in the involved eye, while the eighth was a 10-week-old infant. In the two patients with bilateral glaucoma, the second eye was similar to the first, but without CEU. Three patients had neurofibromatosis, two had facial hemihypertrophy, one had Rieger's anomaly, one had Prader-Willi syndrome, and one had no systemic anomalies. Two had initially been misdiagnosed as having a large pupil in the involved eye and one as having a Horner's syndrome in the uninvolved eye. The finding of CEU in an infant warrants continued observation for the development of glaucoma and disorders of neural crest origin.

Abnormalities, Multiple↗

PubMed1984

Prognostic features in laser trabeculoplasty.

Of 59 phakic eyes with open-angle glaucoma initially treated with laser trabeculoplasty, 45 eyes were followed at least 6 months. Intraocular pressure (IOP) at 6 months was less than 22 mmHg in 37 (82%), of which 25 (81%) were on fewer medications; of 26 eyes followed at least 12 months, IOP was less than 22 mmHg in 24 (92%). Of 49 eyes of patients over 55 years, 43 (88%) had a final IOP less than 22 mmHg, significantly (P less than 0.01) greater than 5/10 eyes of patients under 55 years. Initial IOP correlated positively with reduction of IOP (r = 0.66). IOP was measured 1 h after treatment in 42 eyes, of which 11 (26%) rose greater than or equal to 8 mmHg. This pressure elevation did not significantly affect the success rate.

Argon↗

PubMed1984

Vanadate effects on ocular pressure, (Na+, K+)ATPase and adenylate cyclase in rabbit eyes.

Topical administration of 50 microliter of 1% Na3VO4 caused a significant fall in intraocular pressure (IOP) in the rabbit eye at 90 min. Assay of ATPase of the iris and ciliary body in vitro at 90 min posttreatment showed no differences between control and treated (Na+, K+)ATPase, ouabain sensitive ATPase or vanadate sensitive ATPase. Accumulation of 48V-labelled orthovanadate in iris and ciliary body reached a plateau of 12 pmoles/mg dry tissue weight 4 hr after a single 25-microliter topical dose of 1% orthovanadate. In vitro inhibition of Na+ sensitive ATPase by sodium metavanadate had an IC50 of 1.8 mM, whereas a 1.8-fold stimulation of adenylate cyclase in iris-ciliary body (ICB) membranes in vitro occurred at 10 mM but not at 10 microM Na metavanadate. These results indicate that the vanadate content of the iris and ciliary body at the time of lowered intraocular pressure is too small to inhibit a significant fraction (greater than 10%) of (Na+, K+)ATPase, or cause a significant stimulation of adenylate cyclase, and that other cellular mechanisms are likely to be involved in the ocular hypotensive response to vanadate.

Adenylyl Cyclases↗

PubMed1984

The effect of vanadate on aqueous humor dynamics in cynomolgus monkeys.

Topical administration of 1% vanadate in a formulation designed to enhance penetration lowered intraocular pressure in monkeys' eyes. The decrease in intraocular pressure was associated with significant decreases in aqueous humor flow. Tonographic outflow facility was unaltered by topical vanadate.

Administration, Topical↗

PubMed1984

Effect of topically applied forskolin on aqueous humor dynamics in cynomolgus monkey.

Topical administration of a 1% forskolin suspension significantly reduced intraocular pressure in cynomolgus monkey eyes. The fall in intraocular pressure was associated with a significant (P less than 0.01) decrease in aqueous humor flow measured by a fluorophotometric technique. No significant change was found in tonographic outflow facility or pupillary diameter. A loss of effect on intraocular pressure to subsequent doses of 1% forskolin suspension occurred in cynomolgus monkeys by the third day of twice-a-day treatment.

Administration, Topical↗

PubMed1984

Effect of prostaglandin F2 alpha on aqueous humor dynamics of rabbit, cat, and monkey.

Topical administration of prostaglandin F2 alpha (PGF2 alpha) produced a reduction in intraocular pressure in eyes of rabbits, cats, and cynomolgus monkeys. In rabbit eyes at 5 or 6 hr, 50 micrograms, 100 micrograms, or 250 micrograms of PGF2 alpha caused a significant intraocular pressure reduction with a small miotic effect. Treatment with 500 micrograms, 750 micrograms, or 1000 micrograms of PGF2 alpha lowered intraocular pressure significantly in cat eyes for at least 24 hr with the development of profound pupillary constriction. Administration of 500 micrograms, 750 micrograms, or 1000 micrograms of PGF2 alpha produced a significant reduction of intraocular pressure in monkey eyes lasting at least 24 hr, with an initial hypertensive phase and a small decrease in pupillary diameter in the treated eyes. Tonography revealed an increased facility of outflow simultaneous with the reduction of intraocular pressure in the eyes of cats and monkeys. These increases of outflow facility could not explain completely the reductions in intraocular pressure. The aqueous humor flow measured by fluorophotometry was unaltered in both species, and possible reasons for this finding are discussed. Anterior chamber aqueous humor protein was significantly higher in cat eyes topically treated with 750 micrograms of PGF2 alpha than in the diluent-treated fellow eyes.

Animals↗