Biomedical subjects
S M Podos
Publications and source records attributed to S M Podos.
Thyroid function and the intraocular pressure response to topical corticosteroids.
Baseline thyroxine, thyrotropin (TSH), and triiodothyronine (T3) resin uptake levels were measured in patients classified according to their topical intraocular response to corticosteroids. Results of thyroid studies were similar in patients with primary open-angle glaucoma and noncorticosteroid responsive (NN, intraocular pressure less than 20 mmHg after six weeks of topical 0.1% dexamethasone eyedrops) subjects. Primary open-angle glaucoma was not associated with the increased prevalence of low thyroid function values. The TSH suppression induced by oral dexamethasone was similar in NN subjects and patients with primary open-angle glaucoma. Patients with primary open-angle glaucoma did not demonstrate an increased glucocorticoid sensitivity as related to thyroid function. Thus, the adenohypophysial thyrotropic cell, the major site of dexamethasone inhibition of TSH secretion, does not appear to share the enhanced corticosteroid sensitivity of the eye, the hypothalamus, and the lymphocyte in patients with primary open-angle glaucoma.
Inadvertent substitution of acetohexamide for acetozolamide.
In three cases acetohexamide (Dymelor), an oral hypoglycemic agent, was mistakenly given to patients instead of acetazolamide (Diamox), which had been prescribed for their glaucoma. A number of similarities, including the fact that both medications are 250-mg white tablets, with similar generic and brand names which are generically repackaged medications juxtaposed on the pharmacist's shelf, predispose to the inadvertent substitution of one medication for the other. In one instance a systemic hypoglycemic reaction resulting in head trauma and confusion ended in an emegency hospital admission following the substitution of acetohexamide for acetazolamide.
The effect of hyperthermia on aqueous humor dynamics in rabbits.
Hyperthermia increased intraocular pressure (Po) by approximately 5 mm Hg in rabbit eyes. This increase was not associated with changes in plasma osmolarity, blood lactate, or pH. Episcleral venous pressure (Pv) decreased from a baseline of 11 +/- 1 mm Hg(mean +/- SEM) to 8 +/- 1 mm Hg after one hour of hyperthermia. Outflow facility (c) as measured by tonography remained unchanged. Aqueous humor flow [c(Po - Pv)] as estimated by tonography increased by about 126%. The elevation of intraocular pressure was not prevented by aspirin pretreatment nor altered by unilateral optic nerve transection.
Effect of the ionophore A23187 on chloride transport across isolated frog cornea.
The ionophore A23187 at a concentration of 10(-7) to 10(-5) M stimulated active transport of Cl across the isolated frog cornea. The ionophore had no effect in a Cl-free medium. Both unidirectional Cl fluxes were increased by A23187. The electrical resistance was decreased, and this can be totally accounted for by the increment in passive Cl fluxes. The effect of A23187 on Cl transport and permeability mimicked the effects of cyclic AMP, isoproterenol, and epinephrine. A23187 had no effect when the corneas were fully stimulated by epinephrine or isoproterenol. A23187 produced normal stimulation of the SCC in corneas pretreated with alpha- and beta-adrenergic blockers. The stimulation of the SCC by A23187 was dependent on the presence of Ca in the Ringer solution. Excess Ca (10 mM) resulted in a reduced response. Increasing the Mg concentration in the medium reduced the stimulation of the SCC with Ca concentrations of 0.1-5 mM, but prevented the relative inhibition of 10 mM Ca. Intracellular Ca concentration seemed to regulate Cl permeability of the cornea.
A department of ophthalmology: a personal view.
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Effect of imidazole on ionophore-induced ocular hypertension.
The effect of intraperitoneal injections of imidazole on the elevation of intraocular pressure produced by the topical application of the cation ionophores A23187 or X537A was studied in rabbits. Pretreatment with 200 mg./kg. imidazole completely inhibited the ocular hypertension induced by 1.0 percent A23187. The elevation of intraocular pressure produced by 0.5 percent X537A was not blocked by pretreatment with imidazole.
Acidosis, alkalosis, and aqueous humor dynamics in rabbits.
Systemic acidosis induced by intravenous administration of hydrochloric acid lowered intraocular pressure in unanesthetized rabbits. Aqueous humor flow was reduced by approximately 50%, as measured by the iodide method and as calculated from tonographic data. Outflow facility, episcleral venous pressure, plasma osmolality, blood pressure, pulse, and body temperature were not altered by systemic acidosis. Systemic alkalosis induced by intravenously administered sodium bicarbonate was associated with an increased intraocular pressure. Aqueous humor flow following systemic alkalosis was increased by approximately 100%, as measured by the iodide method and as calculated from tonographic data. Alkalosis was not associated with alterations in outflow facility, episcleral venous pressure, plasma osmality, blood pressure, pulse, or rectal temperature.
Topical corticosteroid therapy and pituitary-adrenal function.
Systemic absorption has been reported after the use of corticosteroid eye drops. Prolonged use could result in adrenocortical insufficiency and an associated adrenal crisis under stressful situations. For that reason, we studied the hypothalamic-pituitary-adrenal axis of patients receiving corticosteroid eye drope. Fifteen patients were given 0.1% dexamethasone sodium phosphate eye drops, one drop (approximately 1/30 ml) to each eye four times a day for six weeks. This dosage resulted in partial adrenal suppression, manifested by reduced levels of plasma cortisol. However, in each case, the hypothalamic-pituitary-adrenal axis, as evaluated with the use of the oral metyrapone tartrate test, was intact.
Traumatic endophthalmitis caused by an Erwinia species.
A previously healthy 70-year-old white man sustained a plant injury to his left eye while gardening and was admitted here because of an ensuing perforated cornea and endophthalmitis. The lens was opaque and its anterior capsule was ruptured. Culture of fluid obtained by anterior chamber paracentesis yielded a species of the Erwinia herbicolalathyri group (Enterobacter agglomerans). Thirty-seven days after a course of cefazolin and gentamicin therapy, corneal edema necessitated a planned extracapsular cataract extraction. The aqueous humor and lens again revealed the identical Erwinia species in pure culture. The patient received another course of cefazolin and showed improvement after the lens aspiration.
Increased intraocular pressure after third ventricle injections of prostaglandin E1 and arachidonic acid.
Prostaglandin E1 administered into the third ventricle of rabbits produced increased intraocular pressure and body temperature. Similar responses were observed after third ventricle instillation of arachidonic acid, a precursor of prostaglandin E2. Increase of body temperature occurred with lower doses of prostaglandin E1 and arachidonic acid while the intraocular pressure response required larger amounts of these drugs. Pretreatment with aspirin rectal suppositories had no effect on the third ventricle responses induced by prostaglandin E1. Aspirin pretreatment before third ventricle instillation of arachidonic acid blocked the increases of intraocular pressure and temperature.
The effects of dipivalyl epinephrine on the eye.
We treated one eye each of ten patients with ocular hypertension with dipivalyl epinephrine (DPE), a congener of epinephrine. Pupil size and intraocular pressure were measured before and at intervals up to 240 minutes after instillation of a single drop of DPE in concentrations from 0.005 to 0.5%. Concentrations of 0.025% DPE and greater significantly reduced IOP, and mydriasis was induced by concentrations of 0.1% DPE or greater. Comcentrations of 0.1% DPE, instilled twice daily for one month, significantly reduced intraocular pressure during diurnal testing on days 2 and 31. No toxic side effects were noted. The DPE produced dose-related increases of cyclic adenosine monophosphate in the aqueous humor of rabbits.
Valve implants in filtering surgery.
A valve implant for glaucoma incorporated upper and lower intraocular pressure limits for outflow. The device consisted of an open Supramid tube sealed to a Silastic tube with a slit valve. The valve implants had opening pressures of 11 to 16 mm Hg and closing pressures 1 to 3 mm Hg lower. A surgical technique was developed in monkey eyes and applied later in modified form to three patients with glaucoma. In four of seven monkey eyes the implants remained in place and were patent for over one year. Follow-up studies were carried out for over six months in the three patients. In two patients the valve implants were functioning with controlled intraocular pressures. In one patient the implant migrated posteriorly. This was replaced by using a new valve and a buried fixation suture and has since functioned without problem. The valve implants were well tolerated and offered possibilities for predictable intraocular pressures after glaucoma surgery.
Prostaglandins, nonsteroidal anti-inflammatory agents and eye disease.
The prostaglandins produce elevation of intraocular pressure and breakdown of the blood-aqueous barrier. They act via the secondary messenger system, cyclic AMP. Although the pathogenesis of many forms of ocular inflammation, both external and internal, is unclear, it is evident that some forms of ocular inflammation are prostaglandin-mediated, at least in part. Others may be totally mediated by prostaglandin synthesis. At present the corticosteroids are the mainstay of therapy of these conditions. However, the corticosteroids are poor inhibitors of prostaglandin synthesis and have many deleterious side effects such as induction of ocular hypertension, cataract, and infection. The search for new agents that will obviate these side effects and be more specific for the disease process is crucial. The discovery that the mode of action of many nonsteroidal anti-inflammatory agents is via inhibition of prostaglandin synthesis places a premium on elucidating which of these agents is most effective and least toxic in the eye and by which route of administration. The arachidonic acid screening model is ideal for initially choosing which agent has the greatest potential clinically. Arachidonic acid, a PGE2 precursor, when given topically also elevates intraocular pressure and aqueous humor protein, and these effects are blocked by the nonsteroidal anti-inflammatory drugs. This occurs if the arachidonic acid is injected into the vitreous humor, too, providing evidence that this in vivo model involves intraocular mechanisms. Utilizing the arachidonic acid system, a comparative study of nonsteroidal inhibitors of prostaglandin synthesis shows that the most effective of 14 agents were flurbiprofen solution and suspensions of polysorbate-dispersed indoxole, meclofenamic acid, indomethacin, and clonixin. Animal uveitis is not an ideal model for the human condition. Nevertheless, proving the superior efficacy of a screened drug in this system will identify those drugs to be tested in the human disease states. Only after the very few best drugs of this nature are identified should the ultimate steps of human testing be initiated.
The effect of cation ionophores on intraocular pressure.
The ionophores A23187 and X537A, which increase the permeability of cell membranes to calcium and other divalent cations, produced significant elevation of intraocular pressure in rabbits. Topical instillation of these ionophores in concentrations of 1.0 and 0.1 per cent were effective. Aqueous humor protein and facility of outflow were similar in ionophore-treated and control eyes. Pretreatment with indomethacin did not block the intraocular pressure rise induced by A23187. Alterations of intracellular calcium might control cellular processes within the eye as in many other biological systems.
Comparison of ocular prostaglandin synthesis inhibitors.
A comparative study was carried out of the inhibitory effect of 14 nonsteroidal anti-inflammatory compounds, administered topically, on the intraocular pressure and aqueous humor protein elevation induced by arachidonic acid in rabbits. The most effective agents were flurbiprofen solution and suspensions of indoxole (polysorbate-dispersed), meclofenamic acid, indomethacin, and clonixin.
Pilocarpine ocular inserts.
Pilocarpine was administered to a selected group of ocular hypertensive subjects in the form of a synthetic biosoluble matrix inserted into the conjunctival cul-de-sac. Satisfactory lowering of the intraocular pressure resulted, with a minimum of subject intolerance. The decreased pressure response was significant in some cases for greater than 24 hours. Drug delivery by soluble inserts offers promise as a convenient and effective mode of therapy.
Krukenberg's spindles.
Forty-three patients who initially presented with Krikenberg's spindles but with no glaucomatous field defects were observed for an average of 5.8 years in an attempt to evaluate the prognostic implication of spindle presence. Twenty-two of the patients had been followed for a minimum of five years. Analysis of the study population revealed that there were more women than men, (26 vs. 17), the women were older than the men, and more women had positive glucose tolerance tests (25% vs. 0). Only two of the patients, both women, developed glaucomatous field defects during the period of observation. Thus, the presence of a Krukenberg's spindle in a patient with no visual field defect is not a particularly ominous sign.