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Biomedical subjects

D L Epstein

Publications and source records attributed to D L Epstein.

At least 127 records · Page 7Linked to original sources

Obstruction of aqueous outflow by sodium hyaluronate in enucleated human eyes.

Instillation of sodium hyaluronate into the anterior chambers of enucleated human eyes caused a 65% decrease in outflow facility (from 0.33 +/- 0.16 microliters/min/mm Hg to 0.08 +/- 0.02 microliters/min/mm Hg). Vigorous anterior chamber irrigation, performed either immediately or three hours after introduction of the sodium hyaluronate, failed to relieve this obstruction. However, irrigation with hyaluronidase restored the facility values to baseline. Tying limbal or corneal 9-0 nylon sutures (for example, in cataract surgery), followed by instillation of sodium hyaluronate into the anterior chamber and subsequent irrigation, produced an overall decrease of 76% in outflow facility (final outflow values were 0.08 +/- 0.03 microliters/min/mm Hg in eyes with corneal wounds and 0.08 +/- 0.04 microliter/min/mm Hg in eyes with limbal wounds). Postoperative intraocular pressure should be monitored closely when sodium hyaluronate is used in cataract surgery. Irrigating the anterior chamber with balanced salt solution after using sodium hyaluronate does not eliminate the possibility of severe postoperative glaucoma.

Anterior Chamber↗

Morphology and function of the aqueous outflow system in monkey eyes perfused with sulfhydryl reagents.

The aqueous outflow system from anterior chamber to Schlemm's canal was examined by electron microscopy in pairs of enucleated macaque and baboon eyes, perfused via the anterior chamber with mock aqueous humor in one eye and the same fluid with added iodoacetamide (IA) or N-ethyl maleimide (NEM) in the other eye. Many details of the electron micrographs were analyzed in a masked manner using a digitizing bit pad and computer, and also using visual evaluation. Both IA and NEM increased aqueous humor outflow facility, but the morphologic changes induced by IA were quantitatively different from those induced by NEM. Intercellular junctions were not affected by IA, but were disrupted by NEM (P less than 0.01). Vacuoles in the endothelial lining of Schlemm's canal tended to increase in area, but not in number, under the influence of IA, whereas they were not so affected by NEM. No loss of extracellular material was observed in either IA- or NEM-treated eyes. The results indicate that the chemical status of cellular-SH groups may influence aqueous humor outflow facility at multiple sites in the outflow pathway.

Animals↗

Glutathione in calf trabecular meshwork and its relation to aqueous humor outflow facility.

Previous studies have shown that sulfhydryl reagents can alter the facility of aqueous humor outflow but little is known about the sulfhydryl constituents of the aqueous outflow system or the effect of oxidants upon outflow facility. In the present study the concentration of glutathione (GSH) was measured in excised calf trabecular meshwork (TM) and found to be 0.40 mu mol/g wet wt (0.027 mu mol/mg protein). Oxidized glutathione was not detectable in the tissue. TM was found to have significant hexose monophosphate shunt activity as determined by measurement of the oxidation of 14C-1 and 14C-6-labeled glucose in tissue homogenates. The concentration of GSH in TM of enucleated calf eyes could be totally depleted by infusion of medium containing both diamide, which is an oxidant of GSH, and 1,3bis(2-chlorethyl)-1-nitrosourea (BCNU), which is an inhibitor of the enzyme glutathione reductase. The depletion of GSH was found to have no effect on the facility of aqueous outflow. Experiments were also done in which normal and TM GSH-depleted eyes were perfused with medium containing H202. Exposure to H202 produced no effect on outflow facility in the normal eyes but caused a 33% decrease in facility in eyes with the GSH-depleted TM. The results indicate that GSH may not participate directly in regulating aqueous humor outflow but is able to protect TM against H202-induced oxidative damage that would otherwise lead to a decrease in outflow facility.

Amino Acids↗

Additive effect of epinephrine to timolol therapy in primary open angle glaucoma.

Previous studies have suggested that the effect on intraocular pressure resulting from the combined use of timolol and epinephrine might be different when they are administered hours rather than minutes apart. Fourteen patients were randomly assigned to one of two treatment sequences in which 1% epinephrine borate was added either five minutes or three hours after 0.5% timolol maleate. Combined therapy was continued for two weeks, after which epinephrine administration was stopped for a two-week washout period. The patient groups were then crossed over to the other dosage interval. There was an initial enhancement of pressure reduction when epinephrine was added to timolol in both sequences. After crossover, epinephrine was significantly additive to timolol in reducing pressure only when administered three hours after timolol. This additive effect was still present after three months of combined therapy.

Adult↗

Diagnosis and management of lens-induced glaucoma.

Lens-induced glaucoma may occur as either secondary angle-closure or open-angle glaucoma. Dislocation or swelling of the lens can cause pupillary block and subsequent angle-closure glaucoma. Leakage of soluble lens proteins from a relatively intact cataractous lens can result in a severe secondary open-angle glaucoma (phacolytic glaucoma). Heavy molecular weight protein, believed to be of lens origin, has now been identified in 12 of 12 anterior chamber specimens from such patients. This liberated lens protein can directly obstruct the trabecular outflow pathways. After extracapsular cataract surgery or after lens trauma, liberated fragments of lens material may mechanically impair the drainage of aqueous humor through the outflow channels (lens particle glaucoma). The diagnosis and management of these different lens-induced glaucomas are reviewed. With proper recognition, these glaucomas are promptly cured by the surgical removal of the lens (material).

Anterior Chamber↗

Effect of delta 9-tetrahydrocannabinol on monoamine oxidase activity in bovine eye tissues, in vitro.

An investigation was undertaken to analyze the effects of delta 9-tetrahydrocannabinol (THC) on monoamine oxidase (MAO) activity from calf ocular tissues. Ciliary processes, retina, trabecular meshwork, choroid, and iris all demonstrated significant MAO activity in decreasing order of magnitude. THC in concentrations from 10(-8)M to 10(-12)M stimulated MAO activity in extracts from all five tissues, except for iris at 10(-8)M. Maximum stimulation of MAO activity occurred at the 1 x 10(-12)M level for all tissues. Retina, followed next by trabecular meshwork and then ciliary processes, exhibited the largest increase in MAO activity at 10(-12)M THC. This latter effect could possibly by related to the influence of THC on intraocular pressure.

Animals↗

N-ethylmaleimide increases the facility of aqueous outflow of excised monkey and calf eyes.

Freshly enucleated eyes were quantitatively perfused via the anterior chamber at 15 mm Hg pressure with various concentrations of the sulfhydryl (-SH) agent. N-ethylmaleimide (NEM). In the monkey eye a dosage of 9.4 mM NEM produced a 108% increase in facility of outflow. In calf eyes a dosage of NEM of 4.7 mM or greater also produced a significant increase in outflow facility. At the threshold dosage of 4.7 mM NEM there was only slight (12%) inhibition of glycolysis in the calf meshwork, which was excised after perfusion. The results suggest that the effect of NEM on outflow facility is not caused by a metabolic inhibitory action. We propose that alteration of cell membrane -SH groups in the outflow pathways can influence aqueous outflow resistance.

Animals↗

Timolol and epinephrine in primary open angle glaucoma. Transient additive effect.

A randomized, double-blind clinical study was conducted on patients with primary open angle glaucoma to determine whether timolol and epinephrine have an additive effect in lowering intraocular pressure. Sixteen patients were randomly assigned to one of two treatment sequences (timolol alone, supplemented after two weeks with epinephrine, and vice versa). An initial additive effect in lowering IOP was found in both sequences. However, after several weeks of combined therapy, complete loss of additive effect was found. Patients who were treated first with epinephrine for two weeks and then supplemented with timolol had significantly lower IOPs, for at least two weeks, than patients in the reverse treatment sequence. Epinephrine treatment alone caused a significant increase in facility of outflow, but this effect did not occur with simultaneous timolol treatment. The results are discussed in terms of possible fundamental beta- and alpha-adrenergic influences on aqueous dynamics and their potential clinical relevance.

Adult↗

The influence of supplemental sodium acetate on carbonic anhydrase inhibitor-induced side effects.

A double-masked, randomly assigned, crossover trial of the effect of supplemental two-weak courses of sodium acetate (90 mEq/day) and placebo on carbonic anhydrase inhibitor (CAI)-induced side effects of malaise, fatigue, and others ("malaise symptom complex") was performed in 28 patients. Fifteen patients (54%) experienced significant improvement while receiving supplemental sodium acetate compared with five (18%) receiving a placebo. A relationship was observed between the clinical efficacy of the acetate supplementation and the measured improvement in serum carbon dioxide combining power. No changes in intraocular pressure were observed when supplemental sodium acetate was given. The results confirm the beneficial effect of supplemental alkalinization for such CAI-induced symptoms in somewhat less than half of the affected patients and suggest the need for long-term studies in which the dosage of sodium acetate is titrated in relation to measured changes in the level of metabolic acidosis.

Acetates↗

Separate and combined effects of timolol maleate and acetazolamide in open-angle glaucoma.

We compared the intraocular pressure-decreasing effect of timolol maleate alone, acetazolamide alone, and combined timolol and acetazolamide therapy in nine patients with bilateral chronic open-angle glaucoma. Timolol decreased intraocular pressure at least as effectively as acetazolamide. The two medications together were more effective than either medication alone, but they did not have a fully additive effect. Episcleral venous pressures and outflow facilities did not vary significantly with any of the three treatment regimens.

Acetazolamide↗

The effect of timolol and acetazolamide on transient intraocular pressure elevation following cataract extraction with alpha-chymotrypsin.

Elevated intraocular pressure (IOP) early after cataract extraction with alpha-chymotrypsin is a well-described, common occurrence. To study the incidence of pressure increase and the efficacy of medical therapy, IOP was monitored every 12 hours beginning on the first postoperative day in 68 patients after otherwise uncomplicated intracapsular cataract extraction performed with one milliliter of alpha-chymotrypsin and wound closure with multiple sutures. Patients were randomly assigned to one of three groups: treatment with oral acetazolamide, treatment with topical timolol, or no treatment. Without prophylactic treatment, the prevalence of pressure elevation at 24 hours postoperatively was 69% with IOP greater than or equal to 25 mm Hg; 29% with IOP greater than or equal to 40 mm Hg. This was independent of the type of sutures used (10--0 nylon or 9--0 silk). The patients of four different surgeons had similar rates of occurrence of postoperative glaucoma. Both timolol and acetazolamide were essentially equally effective in lowering IOP in these patients. No adverse side effects were observed. With these effective treatments available if needed, we believe that routine monitoring of the IOP by applanation tonometry during the early postoperative course provides a good opportunity for reducing the risk of complications from excessive intraocular pressure.

Acetazolamide↗

Study of the additive effect of timolol and epinephrine in lowering intraocular pressure.

A randomised, double-masked clinical study was conducted in patients with primary open-angle glaucoma to determine if timolol and epinephrine have an additive effect in lowering intraocular pressure. Sixteen patients were randomly assigned to one of 2 treatment sequences (timolol alone, supplemented after 2 weeks with epinephrine, and vice versa). An initial additive effect in lowering intraocular pressure was found in both sequences. However, after several weeks of combined therapy complete loss of additive effect was found. Patients who were treated first with epinephrine for 2 weeks and then supplemented with timolol had significantly lower intraocular pressures for at least 2 weeks than patients in the reverse treatment sequence. Epinephrine treatment alone caused a significant increase in facility of outflow, but this effect did not occur with simultaneous timolol treatment. The results are discussed in terms of possible fundamental beta and alpha adrenergic influences on aqueous dynamics and their potential clinical relevance.

Adult↗

Effect of iodoacetamide perfusion on outflow facility and metabolism of the trabecular meshwork.

Freshly enucleated eyes were quantitatively perfused via the anterior chamber with varying dosages of iodoacetamide at constant pressure. Iodoacetamide caused a significant increase in facility of outflow in a dose-response manner in calf and monkey eyes. Almost complete inhibition of glycolysis in the calf trabecular meshwork was produced by a dosage of iodoacetamide that was too low to appreciably alter the facility. A similar response was produced by a higher dosage, which did significantly increase the facility. Our results, taken together with what is known of the properties of iodoacetamide, suggest that cellular sulfhydryl groups may be involved in a mechanism for aqueous flow through the trabecular meshwork and that iodoacetamide probably acts directly on cellular permeability rather than by inhibition of glycolysis or interference with the production of energy in the trabecular meshwork.

Animals↗

Effect of combined 1% cyclopentolate-10% phenylephrine eye drops on systemic blood pressure of glaucoma patients.

Sixty-two patients with glaucoma had eye drops containing 1% cyclopentolate hydrochloride and 10% phenylephrine hydrochloride applied two or three times to one or usually both eyes to dilate their pupils as part of routine eye examinations. Systemic (brachial) blood pressure was monitored before and after drug application. Fifty of the patients had either no change in blood pressure or a decrease. Only two patients had a rise of 20 mm Hg or more in either systolic or diastolic blood pressure. In these two cases the increases were 34/4 and 22/20 mm Hg. Ten patients had an increase ranging from 10 to 20 mm Hg in either systolic or diastolic pressure. The results suggest that a clinically dangerous rise in systemic blood pressure from use of these drops is not common. However, to lessen the risk further, it seems advisable to use drops containing 10% phenylephrine only when lower concentrations are ineffective in dilating the pupils.

Aged↗

Exfoliation glaucoma: a quantitative perfusion and ultrastructural study.

The aqueous outflow systems of both eyes from a patient with well documented exfoliation syndrome were studied postmortem by quantitative perfusion and scanning and transmission electron microscopy. This provided a rare opportunity to correlate clinical and postmortem findings. the right eye was phakic with early glaucoma. The left eye was aphakic with moderately severe glaucoma prior to the cataract surgery. The eyes were fixed at a perfusion pressure of 25 mm Hg. In both eyes the spaces of the corneoscleral trabecular meshwork were open and mostly free of exfoliation material. The trabecular cells appeared normal and contained no exfoliation material. Failure to take up exfoliation material contrasts with the known tendency of these cells to take up pigment and other particles. The main pathology involved destruction of Schlemm's canal and accumulation of exfoliation material in the juxtacanalicular region of both eyes. The changes in Schlemm's canal and the juxtacanalicular region appeared sufficient to account for increase in resistance to aqueous outflow.

Aged↗

Acetazolamide dosage forms in the treatment of glaucoma.

Patients with chronic glaucoma had a carefully scheduled series of intraocular pressure measurements before and after taking acetazolamide for one week at the following dosages: none, 500 mg of sustained-release capsules once a day, 500 mg of capsules twice a day, and 250 mg of tablets four times a day. A capsule taken once a day, which is better tolerated than one taken twice a day by some patients, offers a substantial pressure-lowering effect that lasts at least 23 hours, although the magnitude of the pressure lowering is less than with higher dosages. One capsule twice a day appears to be as effective in the regulation of IOP as one tablet four times a day. The 45% reduction in outflow pressure is achieved with an acetazolamide serum concentration in the range of 15 to 20 micrograms/mL.

Acetazolamide↗