Biomedical subjects
Publications and source records attributed to J S Mindel.
A 21-year-old woman with neurofibromatosis type 1 (NF-1) had a unilateral congenital Horner's syndrome with resultant hypopigmentation of the affected iris. Lisch nodules, which are melanocytic hamartomas, were similar in number, size, and pigmentation in both eyes. The present findings suggest that the formation of Lisch nodules is not influenced by the presence or absence of sympathetic innervation of the iris.
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E-10-hydroxynortriptyline, a metabolite of nortriptyline with half the norepinephrine re-uptake blocking potency of the parent drug, but only 5% of its anticholinergic effect, was as effective as cocaine in demonstrating ocular sympathetic paresis. In five rabbits with unilateral superior cervical ganglionectomies, bilateral 5% cocaine HCl or E-10-hydroxynortriptyline maleate eye drops increased (P less than 0.001) the mean +/- SE anisocoria at 1 h by 1.84 +/- 0.03 mm or 2.16 +/- 0.33 mm, respectively. A single drop of E-10-hydroxynortriptyline did not alter corneal thickness or endothelial cell count.
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Ingestion of the rat poison N-3-pyridylmethyl-N'-p-nitrophenylurea (PNU) produced ocular toxicity in three humans and in an animal model, the Dutch Belted rabbit. The electroretinogram b wave was especially susceptible to the effects of the rodenticide, and the target tissue appeared to be the retinal pigment epithelium. Injection of PNU itself did not produce ocular toxicity. The poison had to be administered orally. Gentamicin administered orally with PNU prevented the ocular toxicity. Presumably this antibiotic killed those gastrointestinal bacteria responsible for PNU's metabolism into an ocular toxin. L-tryptophan, a known antidote for the lethal effects of PNU, was an antidote for the ocular toxicity when administered orally but not when administered parenterally.
Topical application of the H2-histamine receptor agonist, dimaprit (S-[4-N,N-dimethylaminopropyl]isothiourea), produced eosinophil chemotaxis into the anterior segment of rabbit eyes only when an H2-antagonist was co-administered. Nordimaprit (S-[4-N,N-dimethylaminoethyl]isothiourea), a structural homologue of dimaprit that lacked activity at histamine receptors, produced eosinophil chemotaxis whether or not an H2-antagonist was co-administered. Onset of eosinophil chemotaxis began after 2 or more days of treatment, and was accompanied by corneal edema, opacification, and ocular inflammation. There was no concurrent eosinophilia in the peripheral blood or in the conjunctiva. The response occurred in pigmented and albino rabbit eyes, and was facilitated by prior co-administration of proparacaine eye drops. Another dimaprit homologue without activity at histamine receptors, homodimaprit (S-[4-N,N-dimethylaminobutyl]isothiourea), did not produce eosinophil chemotaxis when applied topically, nor did the H2-agonists impromidine, histamine, or 4-methylhistamine, whether co-administered with an H2-antagonist or not. It was concluded that dimaprit and nordimaprit produced a selective eosinophil chemotaxis unrelated to H1- and H2-histamine receptor activity. However, the H2-agonist activity of dimaprit appeared to inhibit this response unless neutralized by an H2-antagonist. Topical application of dimaprit with an H2-antagonist or nordimaprit alone may allow large numbers of non-degranulated eosinophils, free of other cell types, to be harvested from the aqueous humor.
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D,L-dipivefrin hydrochloride was administered bilaterally to rabbit eyes five or 150 minutes after unilateral application of a cholinesterase inhibitor. Aqueous humor levels of D,L-epinephrine, measured 30 minutes later by high-performance liquid chromatography, were not significantly different in the two eyes. Nonenzymatic conversion of D,L-dipivefrin to D,L-epinephrine was measured in tissue-free (pH 7.4) solutions; after three hours less than 1% of D,L-dipivefrin became D,L-epinephrine. Homogenates of corneal epithelium were 16 times more effective in converting D,L-dipivefrin to D,L-epinephrine than after heat-inactivation. The ocular hypotension produced by 0.25% D,L-dipivefrin eyedrops was unaffected by prior administration of 0.25% echothiophate iodide eyedrops provided the D,L-dipivefrin was administered after the echothiophate-induced ocular hypertensive phase. It was concluded that D,L-dipivefrin was converted to D,L-epinephrine in vivo primarily by enzymatic hydrolysis and that cholinesterase inhibitors did not affect this conversion.
Dipivefrin is an antiglaucoma prodrug that is hydrolyzed to the active drug, epinephrine, by esterases in the cornea. Since cholinergic antiglaucoma agents are frequently used in combination with adrenergic agents, it was of interest to determine the effects of a commonly used irreversible cholinesterase inhibitor, echothiophate (Phospholine) iodide, on the dipivefrin esterases. In vitro studies showed that echothiophate is a competitive, reversible inhibitor of the soluble corneal dipivefrin esterases. In vivo studies substantiated the reversible nature of echothiopate inhibition, since no inhibition of dipivefrin hydrolysis could be detected 1 3/4 hours after echothiophate treatment and as early as 15 minutes after dipivefrin application.
Imidazole activates synthesis of acetylcholine by choline acetyltransferase. Pilocarpine hydrochloride, an imidazole derivative, was investigated for its activation effect. In vitro, millimolar concentrations of pilocarpine significantly activated human ciliary body and retinal and rabbit corneal epithelial, iris-ciliary body, and retinal choline acetyltransferases. Concentrations greater than 100mM pilocarpine inhibited acetylcholine synthesis. In vivo, 1% or 4% pilocarpine eyedrops given every 30 minutes for four applications failed to significantly alter rabbit ocular acetylcholine levels. There was a tendency for pilocarpine-treated eyes to have lower levels of acetylcholine. Although pilocarpine altered acetylcholine synthesis by human and rabbit ocular tissues in vitro, this phenomenon could not be demonstrated in rabbits in vivo. However, because tissues of intact rabbit eyes degrade pilocarpine, the possibility remains that this drug can alter acetylcholine synthesis when applied to the intact human eye.
The nictitating membrane, corneal epithelium, and corneal stroma were investigated as drug reservoirs. A hydrophilic drug, D,L-epinephrine HCl, or a lipophilic drug, chloramphenicol, was applied topically to rabbit eyes. Tissue levels of radioactive drug-plus-metabolites and unmetabolized epinephrine were assayed up to 24 hrs later. On a per-mg-tissue basis, concentrations of epinephrine-plus-metabolites in the stroma-endothelium were similar to or higher than those in the epithelium. The percentages of radioactivity representing unmetabolized epinephrine in the stroma-endothelium were found to be similar to or higher than those in the epithelium. On a per-mg-tissue basis, concentrations of chloramphenicol-plus-metabolites were significantly higher in the epithelium than in the stroma-endothelium during the first 130 min after drug application. While the physical properties of these drugs determined whether a higher concentration was found in the epithelium or stroma-endothelium, the ninefold greater mass of the stroma-endothelium made it the major drug reservoir on a per-whole-tissue basis. The presence or absence of a nictitating membrane had little effect on the level of either drug in the epithelium, stromal-endothelium, or aqueous humor.
Ten patients with partial temporal visual field defects were examined with a modified tangent screen projection perimeter (Auto-Plot). Defects demonstrated with an isopter for chromatic recognition of a 3-mm red stimulus could always be reproduced with an isopter for achromatic recognition of a dim, 3-mm white stimulus. The red-white intensity ratio producing equivalent fields remained constant for a given patient but varied from subject to subject (range, 3.0 to 7.5; mean, 5.7; SD, 1.8). Thus, red functioned as dim white, but no single fixed ratio of intensities was applicable to all subjects. Visual field testing with 1 foot-candle of tangent screen illumination permitted subjects to adapt to dark. As retinal sensitivities increased, the corresponding visual field steadily enlarged for 30 minutes. This effect was greater in the pathologic temporal fields, which increased relatively more than intact nasal fields. The result was poor visual field reproducibility with time.
The triad of hyperprolactinemia, ophthalmoplegia, and radiologic abnormalities of the sell turcica suggest a tumor in the area of the pituitary gland. A new association--bilateral intracavernous carotid aneurysms--is presented. Two elderly women had extraocular muscle palsies and elevated serum prolactin levels of 71 and 32 ng/ml (normal: less than 20 ng/ml). In the former, a high-resolution computed tomography scan made after contrast medium injection was incorrectly interpreted as demonstrating a pituitary tumor; cerebral arteriography revealed bilateral aneurysms. In the other patient, a computed tomography scan after contrast medium injection demonstrated the bilateral aneurysms, and these were confirmed by radionuclide angiography.
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We measured the ocular positions of conscious and anesthetized subjects from photographs. We obtained the conscious basic horizontal deviation by using the cover-uncover test. Intravenously administered succinyldicholine chloride, 2 mg/kg of body weight, returned the eyes of 15 anesthetized volunteers to positions that agreed well with those of their conscious horizontal basic deviations in the primary position. The mean ratio (+/- S.E.) calculated by dividing the horizontal interlimbal distance 90 seconds after drug injection by that of the same subject's horizontal interlimbal conscious basic deviation was 0.99 +/- 0.01. This result supported the theory that the multiply innervated (en grappe) extraocular muscle fibers were responsible for the basic deviation. Macaca nemestrina monkeys and baboons proved to be unsuitable primate models for the human succinyldicholine response. In humans, the drug-induced ocular position was often vertically above or below the primary position. The associated horizontal deviation appeared to follow the physiologic V pattern, being more divergent if the eyes were rotated up and more convergent if the eyes were rotated down. In one third of the subjects this vertical deviation resulted in drug-induced horizontal interlimbal distances that disagreed by more than 5% with those of the conscious basic deviation in the primary position. This effect makes succinyldicholine of little value for making quantitative estimates of the amount of ocular muscle surgery to be performed during strabismus correction procedures. We injected succinyldicholine at the conclusion of strabismus surgery in eight subjects to determine if the drug-induced ocular positions would predict the postoperative results. The muscles operated on responded as though temporarily paretic. The drug-induced ocular positions bore no resemblance to the postoperative results.