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Biomedical subjects

T Krupin

Publications and source records attributed to T Krupin.

At least 37 records · Page 2Linked to original sources

5-Fluorouracil in initial trabeculectomy. A prospective, randomized, multicenter study.

PURPOSE: Postoperative subconjunctival 5-fluorouracil (5-FU) injections increase the success of filtration surgery in eyes with prior filtration failure or cataract removal and in eyes with secondary glaucoma. The authors evaluate the safety and benefit of adjunctive 5-FU in eyes undergoing initial trabeculectomy. METHODS: Patients with phakic, uncontrolled, open-angle glaucoma who were undergoing initial trabeculectomy were prospectively assigned to the 5-FU group on the first postoperative day. Patients in this group received five 5-mg injections during 2 weeks after surgery. Patients in the control group received no injections. RESULTS: Preoperative intraocular pressure (IOP) and number of antiglaucoma medications were similar in the 5-FU (n = 32) and control (n = 30) groups. Transient superficial punctate keratopathy was the only postoperative complication that occurred more frequently (P < 0.05) in the 5-FU (14 eyes) than in the control eyes (3 eyes). Patients were followed for a minimum of 1 year or until a study endpoint was reached: IOP of 21 mmHg or greater with maximum medical therapy (2 5-FU eyes and 8 control eyes; P < 0.03) or cataract removal after filtration (5 treated and 3 control eyes). At last follow-up (mean, > 20 months), IOP and the number of antiglaucoma medications were significantly lower (P < 0.02) in the 5-FU eyes (IOP, 12.0 +/- 1.3 mmHg; medications, 0.2 +/- 0.1) than in the control eyes (IOP, 16.8 +/- 1.3 mmHg; medications, 0.8 +/- 0.2). Intraocular pressure was 20 mmHg or lower in 94% of 5-FU eyes and in 73% of control eyes (P < 0.03) and 16 mmHg or lower in 84% of 5-FU eyes and in 57% of control eyes (P < 0.02). CONCLUSIONS: Adjunctive 5-fluorouracil increases the rate of success, decreases the level of postoperative IOP, and reduces the need for postoperative antiglaucoma medication in eyes with open-angle glaucoma undergoing initial trabeculectomy.

Aged↗

Dye coupling of rabbit ciliary epithelial cells in vitro.

PURPOSE: To examine the in vitro properties of gap junctions on the isolated rabbit ciliary epithelium. METHODS: Intracellular potential was measured and lucifer yellow (5% in 1 M LiCl) was iontophoretically injected into a ciliary epithelial cell. Fixated tissue was examined with a laser confocal microscope. RESULTS: Dye spread was observed throughout both layers (horizontally and vertically) of the ciliary epithelium adjacent to the injected cell that was more intensely labeled. Dye reflux did not occur at the site of microimpalement. Microiontophoretic dye injection in a bathing solution with a high Ca2+ (10 mM) or an acidic pH (6.3) completely inhibited cell-cell dye coupling in the rabbit ciliary epithelial cells. CONCLUSIONS: Laser confocal microscopy of intracellularly injected lucifer yellow dye demonstrates the physiologic presence of gap junctions between both ciliary epithelial layers. Extracellular acidosis and high concentration of extracellular Ca2+ cause loss of cell-cell coupling in the rabbit ciliary epithelium.

Animals↗

Apraclonidine and argon laser trabeculoplasty.

Sixty patients with medically uncontrolled open-angle glaucoma (intraocular pressure greater than 21 mm Hg) were randomly assigned to one of two treatment regimens with apraclonidine before undergoing 360-degree argon laser trabeculoplasty. One drop of apraclonidine 1% was instilled one hour before and immediately after laser treatment in 30 eyes or apraclonidine was delivered only after trabeculoplasty in 30 eyes. Intraocular pressure before laser treatment, number of antiglaucoma medications, and the laser treatment settings were comparable between the two groups. The mean and percent change in intraocular pressures were similar in both treatment groups one and two hours after trabeculoplasty. One drop of apraclonidine 1% instilled immediately after argon laser trabeculoplasty prevented intraocular pressure increase one hour and two hours postoperatively as effectively as its instillation both one hour before and immediately after laser treatment.

Administration, Topical↗

Whole cell patch clamping of ciliary epithelial cells during anisosmotic swelling.

Anisosmotic cell swelling triggers a regulatory volume decrease (RVD) in cell lines derived from human nonpigmented ciliary epithelium. Measurements of cell volume have indicated that the RVD reflects activation of K+ and/or Cl- channels. We have begun to characterize the putative channels by whole cell patch clamping. The results obtained by altering the external K+ and Cl- concentrations and by adding 20-50 microM quinidine or 1 mM Ba2+ indicate that K+ conductances contribute substantially and Cl- conductances contribute very little to the total membrane conductance (GT) under baseline isotonic conditions. Reducing the external osmolality by 20-50% reversibly and reproducibly increased GT by an order of magnitude. Data obtained from ion substitutions and the channel blockers quinidine and 5-nitro-2-(3-phenylpropylamino)-benzoate indicate that most of the hypotonicity-induced conductance reflects stationary Cl(-)-channel activity. The contribution of new K(+)-channel activity was small at intracellular free Ca2+ concentrations of 10 or 200 nM. We conclude that the RVD triggered by bath hypotonicity primarily reflects increased Cl(-)-channel activity.

Chlorides↗

Effect of bicarbonate on intracellular potential of rabbit ciliary epithelium.

Extracellular HCO3- hyperpolarizes the intracellular potential and makes the aqueous medium negative with respect to the stromal surface of the rabbit ciliary epithelial syncytium. The bases for these observations have been unclear. We have been studying the bicarbonate-induced hyperpolarization (BIH) with sustained intracellular recordings for periods as long as 1-2 hrs. The BIH was observed [6.0 +/- 0.4 mV (mean +/- SE, N = 22)] even when the external pH was clamped constant by appropriately changing the CO2 tension. External HCO3- was required since aeration with CO2 at low external pH did not replicate the BIH. DIDS [4,4'-diisothiocyano-2,2'-disulfonic acid] did not abolish the effect. The hyperpolarization is unlikely to reflect the pH dependence of K+ channels alone, since the effect was not reduced by either 2 mM Ba2+ alone or 2 mM Ba2+ together with 50-100 microM quinidine. The BIH depends directly or indirectly on external Na+, since the sign of the polarization response was reversed either by replacing Na+ with N-methyl-D-glucamine or by blocking the Na+,K(+)-exchange pump with 50-100 microM ouabain. Replacement of external Cl- with NO3- or application of the Cl(-)channel blocker NPPB [5-nitro-2-(3-phenylpropylamino)-benzoate] depolarized the membrane and reversed the sign of the BIH. The response of the ciliary epithelium to HCO3- is complex and may arise from several mechanisms. We suggest that one important element is an anion channel whose conductance is reduced by bicarbonate and whose reversal potential is indirectly dependent on the operations of the Na+,K(+)-pump and a Cl(-)-linked symport.

Animals↗

Effects of adrenergic agents on transepithelial electrical measurements across the isolated iris-ciliary body.

Transmembrane electrical measurements were performed on the isolated rabbit iris-ciliary body to study direct effects of adrenergic drugs on the ciliary epithelium. Alpha-adrenergic agonists (epinephrine, norepinephrine, or phenylephrine) lowered the short-circuit current (SCC) in a dose-dependent fashion relative to which chamber side the drug was added: simultaneous addition to both chambers greater than blood side only greater than aqueous side only. Pretreatment (5 x 10(-5) M) with the non-selective beta-adrenergic antagonist timolol had no effect while the non-selective alpha-adrenergic antagonist, phentolamine, completely prevented the alpha agonist-induced decrease in SCC. The alpha-adrenergic response was mediated by the alpha 1 subtype since prazosin, but not yohimbine, blocked the induced reduction in SCC. The beta-adrenergic agonist isoproterenol caused a dose-dependent decrease in the SCC. The decrease was similar when the drug was added to only the blood side or to both sides of the chamber. Addition to only the aqueous chamber had no effect. Pretreatment with beta-adrenergic antagonists blocked the isoproterenol response: non-selective = selective beta 2 greater than selective beta 1. The isoproterenol-induced decrease in SCC was also blocked by non-selective alpha-adrenergic antagonists. The response was mediated by the alpha 1 subtype since prazosin, but not yohimbine, blocked the isoproterenol response. This suggests that isoproterenol interacted with the alpha 1-adrenergic sensitive pathway in the rabbit ciliary process.

Animals↗

Update: diagnostic concepts in open-angle glaucoma.

New advances aided by computerized technology have been made in the detection and quantification of glaucomatous psychophysical and optic-nerve abnormalities. The aim of all these techniques is earlier detection of intraocular pressure-related damage to the optic nerve. In addition, improvements in the sensitivity and specificity of diagnostic modalities offer the possibility to better quantitate and therefore monitor the dynamics of the glaucomatous process. These devices offer great potential for pathophysiologic investigations. However, expanded research needs to be performed prior to the clinical application of the techniques discussed in this review. The future looks promising for improved methods in the diagnosis and management of glaucoma.

Glaucoma, Open-Angle↗

Temporal contrast sensitivity loss in primary open-angle glaucoma and glaucoma suspects.

The need for more sensitive tests for the early detection of compromised visual function in glaucoma is established by anatomic and psychophysical evidence of damage occurring to optic nerve fibers in eyes with normal visual fields. The results are reported of temporal frequency testing on 51 glaucoma suspects without visual field loss in either eye, 52 glaucoma patients with visual field deficits in the tested eye, and 11 normal subjects. Modulation transfer functions were obtained using a sinusoidally flickering 5 degrees spatially uniform white field viewed with central fixation and plotted at six frequencies from 5-30 Hz. The results showed a frequency-specific sensitivity loss centered at 15 Hz and a nonfrequency-specific mean sensitivity loss, that was greater, on average, in glaucoma patients than in suspects. Sensitivity losses of both kinds were seen in most glaucoma patients, but only in a minority of glaucoma suspects. About 12% of suspects were indistinguishable from the lowest performing one third of these glaucoma patients. A smaller number of suspects appeared to form a second mode in the frequency distribution for temporal sensitivity at 15 and 25 Hz. In patients with glaucoma, age was found to be a significant factor associated with the magnitude of mean sensitivity loss. Age was not a significant factor contributing to sensitivity loss in individual suspect data as measured by regression analysis, but it contributed to a small and consistent sensitivity loss across frequency for group-averaged data in those older than 55 years of age.

Adult↗

Halogenated inhalation anesthetic agents decrease transepithelial electrical measurements across the isolated iris-ciliary body.

Transmembrane electrical measurements were performed on the isolated rabbit iris-ciliary body (I-CB) to study the direct effects of halogenated inhalation anesthetic agents on the ciliary epithelium. Addition of either halothane, enflurane, or isoflurane to the control 95% O2:5% CO2 gas mixture resulted in a dose-dependent decrease in the short-circuit current (SCC) and potential difference (PD). This response was reversible after the anesthetic gas was discontinued. Pretreatment with either alpha-adrenergic or beta-adrenergic antagonists (phentolamine or timolol) had no effect on the halothane-induced decrease in SCC. Delivery of the analgestic gas N2O did not alter baseline electrical measurements across the isolated I-CB.

Analysis of Variance↗

Optic disc topography in patients with low-tension and primary open angle glaucoma.

Computerized optic disc topographic measurements (cup-disc ratio, neuroretinal rim area, disc volume) and automated visual field parameters (total field loss, mean sensitivity) were similar in 48 eyes with primary open angle glaucoma and 27 eyes with low-tension glaucoma. In open angle glaucoma, the neuroretinal rim area was negatively correlated with the cup-disc ratio and the disc volume. Total field loss was positively correlated with the cup-disc ratio and the disc volume and negatively correlated with the neuroretinal rim area. Eyes with low-tension glaucoma showed a negative correlation between neuroretinal rim area and cup-disc ratio, and between total field loss and rim area. However, low-tension glaucomatous eyes did not have significant correlations between disc volume and rim area and between total field loss and cup-disc ratio or disc volume. Cupping in low-tension glaucoma was broadly sloping, resulting in less disc volume alteration.

Aged↗

Effect of patient experience on the results of automated perimetry in glaucoma suspect patients.

The first four Octopus-automated visual field examinations of 29 patients with elevated intraocular pressure but apparently normal optic discs and Goldmann visual fields were studied for the presence of a learning effect on the visual field parameters of mean sensitivity, number of disturbed test locations, total field loss, and short-term fluctuation. A learning effect, if present, would manifest itself as an improvement in the visual field as patients become more experienced with the test. There was no apparent effect of patient experience on the mean sensitivity of the whole visual fields or the mean sensitivity of the test locations within 20 degrees of fixation. There was a significant (P = 0.012) increase in mean sensitivity for the test locations outside 20 degrees of fixation. There were significant (P less than 0.01) improvements in short-term fluctuation, total loss, and number of disturbed points between the first and second visual field examinations. The results indicated that there was a learning effect between the first and second automated visual field in glaucoma suspect patients who had previous experience with manual perimetry. It was not, however, very large in most patients and seems to be present in the peripheral portions of the visual field only. In most cases, it was not necessary to obtain more than two "baseline" examinations unless a patient demonstrated unusually high short-term fluctuation or had visual field defects inconsistent with the remainder of their clinical examination.

Adult↗

Bilateral argon laser trabeculoplasty in primary open-angle glaucoma.

We performed bilateral argon laser trabeculoplasty on 34 patients with medically uncontrolled open-angle glaucoma. Preoperative intraocular pressure was greater than 21 mm Hg, with a less than 3-mm Hg difference between the two eyes. Laser treatment (360 degrees) was performed on both eyes within a three-month interval. Mean (+/- S. D.) baseline intraocular pressure was similar in the first- (26.9 +/- 3.7 mm Hg) and second- (26.5 +/- 3.3 mm Hg) treated eyes. One hour after treatment, four first- and four second-treated eyes had a greater than 30% increase in intraocular pressure. The one-hour change in pressure was highly correlated between the two eyes (r = .794, P less than .0001). Intraocular pressure was reduced (P less than .0001) one, two, and three years after treatment in both the first and second-treated eyes. The percentages of first- and second-treated eyes with a pressure of less than or equal to 21 mm Hg were similar at one, two, and three years. Pressure response between the two eyes was correlated (P less than .0001) at year 1 (r = .815), 2 (r = .757), and 3 (r = .886) after laser therapy.

Adult↗

Volume regulation of cultured, transformed, non-pigmented epithelial cells from human ciliary body.

Electronic cell sizing has been used to measure the volume of cells suspended in isosmotic and in hyposmotic solutions of identical ionic composition. Without inhibitors, the cells displayed a regulatory volume decrease (RVD) following anisosmotic cell swelling with a time constant (tau) of 6.3 +/- 0.9 min (mean +/- S.E.). The RVD was markedly impaired by substituting gluconate for external Cl-, and tau was prolonged by: (i) reducing the chemical gradient favoring K+ loss (by elevating the external [K+] and blocking the Na. K-exchange pump), (ii) blocking the K+ channels with Ba2+, (iii) blocking Cl- channels and Cl-/HCO3 = exchange with DIDS, and (iv) removing external HCO3-. Withdrawing HCO3- may have altered the RVD either directly by inhibiting a Cl-/HCO3- antiport, or indirectly by affecting intracellular pH. The regulatory volume response of ODM Cl-2/SV40 cells is in several respects qualitatively similar to that of non-pigmented epithelial cells of the intact ciliary body. These common characteristics suggest that the cultured cells can serve as a useful model for studying solute and fluid transport across the human ciliary epithelium. The basis for the RVD is likely to be activation of separate K+ and Cl- channels, with or without the parallel operation of coupled K+/H+ and Cl-/HCO3- antiports.

Cell Line, Transformed↗

Postoperative intraocular pressure rise in open-angle glaucoma patients after cataract or combined cataract-filtration surgery.

Postoperative intraocular pressure (IOP) was measured in patients with open-angle glaucoma undergoing extracapsular cataract extraction with a posterior chamber lens implant (ECCE-PC IOL). Patients considered to be under adequate medical glaucoma control had cataract surgery alone or combined with a posterior lip sclerectomy. Patients with medically uncontrolled glaucoma had cataract surgery combined with either a posterior lip sclerectomy or a trabeculectomy. Cataract surgery alone (n = 26) was associated with a significantly (P less than 0.001) increased IOP on postoperative day 1: preoperative IOP, 18.9 +/- 3.6 mmHg; postoperative IOP, 34.2 +/- 12 mmHg. An IOP rise of 10 mmHg or more occurred in 69% of the eyes, whereas 77% of the eyes had an absolute IOP over 25 mmHg. Eyes undergoing combined surgery (n = 42) had a preoperative IOP of 21.3 +/- 4.8 mmHg. On postoperative day 1, the mean IOP was 14.9 +/- 12.0 mmHg. An IOP rise of 10 mmHg or more was observed in 14%, and an IOP over 25 mmHg in 21% of combined surgery eyes. Cataract surgery in eyes with open-angle glaucoma requires careful monitoring and therapy for early postoperative increases in IOP. Combined surgery reduces the frequency and magnitude of, but does not eliminate, this complication.

Aged↗

The ocular hypotensive effects of demeclocycline, tetracycline and other tetracycline derivatives.

Demeclocycline, tetracycline and other tetracycline derivatives lowered intraocular pressure (IOP) in rabbits following intravitreal injection, but the onset of this effect was not evident until 1 or more days after drug administration. Of the drugs tested, demeclocycline was the most active ocular hypotensive agent. Demeclocycline caused a dose-dependent decrease in IOP. The maximum IOP decrease of approximately 12 mm Hg occurred 5 days after intravitreal administration of 0.5 mg, with the effect persisting for over a week. Demeclocycline did not alter tonographically measured aqueous humor outflow facility or episcleral venous pressure. Based on calculated aqueous humor flow rates following 0.2 mg demeclocycline, a 62% decrease in aqueous humor formation occurred 7 days after intravitreal injection. The flow-to-diffusion ratio for ascorbate was reduced 54% 6 days after the intravitreal administration of demeclocycline, a change also consistent with suppression of aqueous humor formation. Anterior chamber aqueous humor protein concentration was increased 6 days after demeclocycline administration. No histologic changes were present in the treated eyes by light microscopy. Intravitreal demeclocycline similarly lowered IOP in cats, with the duration of effect lasting up to 20 days.

Animals↗