Failure of controlled clinical trial data to reach the literature.
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Biomedical subjects
Publications and source records attributed to J S Mindel.
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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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A study was undertaken to determine whether the antiesterase activity of echothiophate iodide would prevent the conversion of dipivefrin to epinephrine. Dipivefrin was administered singly and in combination with echothiophate to 24 adult rabbits. Administration of dipivefrin lowered the intraocular pressure (IOP) 8 +/- 1 mm Hg (P less than .001). When echothiophate was given before and concomitant with dipivefrin, there was no further decrease in IOP compared with that produced by echothiophate alone (5 +/- 1 mm Hg). Addition of epinephrine to eyes receiving dipivefrin plus echothiophate resulted in a significant additional decrease in IOP of 4 +/- 1 mm Hg (P less than .001). When echothiophate was given after dipivefrin had lowered the IOP and both drugs were continued, the IOP rose to baseline levels. These results fit the theory that the esterase converting dipivefrin to epinephrine is inactivated by cholinesterase inhibitors. The clinical use of cholinesterase inhibitors and dipivefrin may be contraindicated.
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Fifty-four subjects with initial intraocular pressures under 20 mm Hg received a different commercial corticosteroid ester of prednisolone or dexamethasone in each eye for three to six weeks. Compliance was controlled. The intraocular pressure responses of the two eyes of a subject were similar. It was concluded that the absorptions of all four corticosteroids were in excess of the minimum amounts needed to maximally elevate pressure. Subjects complained that prednisolone acetate was irritating. Corticosteroid-induced uveitis developed in 3% (3) of the eyes.
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In a study of 27 cases of surgery for cataract extraction, mepivacaine 2% with hyaluronidase was found to shorten the induction times of facial nerve and retrobulbar blocks when compared to injections of mepivacaine 2% alone. The mean induction time of facial nerve blocks with hyaluronidase was 1.3 +/- 0.4 minutes. This was significantly (P less than .01) shorter than the mean induction time without hyaluronidase, 2.9 +/- 1.8 minutes. The use of hyaluronidase significantly (P less than .02) shortened the induction time of retrobulbar blocks. The median induction time with hyaluronidase was three minutes, whereas that without hyaluronidase was ten minutes. However, the use of hyaluronidase did not significantly (.25 less than P less than .50) alter the success rate of retrobulbar blocks.
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The variation of choline acetyltransferase activity in ocular tissues of four mammalian species, rabbits, cats, cattle, and man, was determined. Enzyme activity of irides and ciliary bodies, i.e., parasympathetically innervated structures, tended to be similar in all four species. Two exceptions were bovine irides and human ciliary bodies; these two tissues had higher enzyme activities. Choline acetyltransferase activity was present in the corneal epithelium of rabbit, bovine, and human eyes, but little or none could be detected in that of cats. Feline retina and pigment epithelium-choroid also contained far less choline acetyltransferase activity than the same tissues in the other three species.
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