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Biomedical subjects

R K Parrish

Publications and source records attributed to R K Parrish.

At least 55 records · Page 3Linked to original sources

The effect of beta irradiation on monkey Tenon's capsule fibroblasts in tissue culture.

Fibroblast proliferation with subsequent bleb scarring is a major cause of filtering surgery failure. To investigate possible antiproliferative effects of beta radiation, owl monkey Tenon's capsule fibroblasts in tissue culture were irradiated to doses of 30, 100, 300, 1,000, and 3,000 rads with a linear accelerator and to doses of 95,285, and 950 rads with a Strontium-90 applicator. The irradiated cell proliferation expressed as the percentage of the non-irradiated control growth on the third and seventh days, respectively, after beta irradiation was: 97% and 96% after 30 rads; 72% and 90% after 100 rads; 48% and 44% after 300 rads; 39% and 14% after 1,000 rads; and 39% and 14% after 3,000 rads. Similar effects on cell proliferation were observed with the Strontium-90 applicator. The inhibitory effect of beta irradiation on fibroblast proliferation in tissue culture suggests that beta irradiation after filtering surgery may reduce postoperative bleb scarring.

Animals↗

Trifluorothymidine and 5-fluorouracil: antiproliferative activity in tissue culture.

The antiproliferative activity of trifluorothymidine (F3TDR) and 5-fluorouracil (5-FU), two cell-cycle-phase-specific antimetabolites, was compared in a tissue culture model of human scleral fibroblasts and rabbit corneal epithelial cells. The mean concentrations required to inhibit human scleral fibroblast proliferation to 50% of the control rate (ID50) after 5 days of exposure were 8.50 micrograms/mL for F3TDR and 0.43 microgram/mL for 5-FU. The corresponding ID50 levels for rabbit corneal epithelial cells were 0.24 microgram/mL and 0.42 microgram/mL. The ID50 of F3TDR was significantly higher than that of 5-FU in human scleral fibroblasts (p less than 0.001) but not in rabbit corneal epithelial cells. F3TDR appears to have no clinical advantage over 5-FU in minimizing corneal epithelial toxicity when given to prevent fibroblast proliferation after glaucoma filtering surgery.

Animals↗

An intraoperative intraocular pressure monitor.

An autoclavable instrument based on piezoelectric principles for intraoperative monitoring of the intraocular pressure is presented. Accurate and rapid recordings of intraocular pressure during various surgical techniques are discussed.

Humans↗

Subconjunctival 5-fluorouracil mechanisms of ocular penetration.

Aqueous, corneal, and tear film 14C 5-fluorouracil (5-FU) levels were measured in rabbit eyes to better understand the mechanisms of intraocular penetration after subconjunctival injection. Significantly higher aqueous and tear 5-FU levels were achieved one hour after administration when the subconjunctival injection was given transconjunctivally rather than percutaneously through the upper lid [aqueous = 65.7 +/- 9.1 micrograms/ml vs 21.3 +/- 5.1 micrograms/ml (mean +/- SE; p = 0.02, 2-tailed t-test); and tears = 5408.8 +/- 357.3 micrograms/ml vs 228.0 +/- 46.4 micrograms/ml (mean +/- SE; p = 0.004, 2-tailed t-test)]. The aqueous 5-FU levels four hours after transconjunctival injection were significantly greater in anesthetized rabbits without blink reflexes than in those with intact reflexes [32.0 +/- 3.2 micrograms/ml vs 13.4 +/- 0.5 micrograms/ml (mean +/- SE; p = 0.026, 2-tailed t-test)]. The corneal 5-FU levels four hours after transconjunctival injection were greatest nearest the injection site. Direct corneal penetration appears to account for the majority of the aqueous 5-FU concentration after subconjunctival injection; however, there may also be diffusion through the limbus.

Animals↗

Preliminary report on corneal incisions created by a hydrogen fluoride laser.

We created corneal incisions in eye bank eyes with a pulsed hydrogen fluoride infrared laser. This laser was selected because its emission spectrum (2.7 to 3.0 micron) closely corresponds to the absorption peak of water in the infrared region. Short pulses (200 nsec) of hydrogen fluoride laser light focused with a cylindrical lens resulting in radiant exposures of 1.3 J/cm2 at the corneal surface created linear cuts in the cornea with minimal thermal damage adjacent to the incision, suggesting that the pulsed hydrogen fluoride laser may be useful for corneal surgery.

Cornea↗

Topical fluorouracil. II. Postoperative administration in an animal model of glaucoma filtering surgery.

Unilateral posterior lip sclerectomies were performed in ten owl monkeys. Five milligrams of fluorouracil was injected subconjunctivally in each operated eye immediately after surgery. Three drops (approximately 2.4 mg/drop) of fluorouracil were instilled ten minutes apart in each operated eye twice daily on postoperative days 1 through 7 and once daily on postoperative days 8 through 15, 17, 19, and 21. One monkey died on the seventh postoperative day; its death could not be attributed to systemic fluorouracil toxicity. All of the operated eyes had filtering blebs after the full course of fluorouracil, but seven also had corneal epithelial defects. By the seventh postoperative week, two of the operated eyes manifested moderately severe corneal opacification. Ten weeks postoperatively, the electroretinographic a- and b-wave amplitudes averaged 17% and 12% less, respectively, in the seven operated eyes without clinically significant corneal opacification than in the unoperated fellow eyes. Only two eyes had blebs after the 12th postoperative week. Histopathologic examination was performed on five eyes, of which only two revealed patent sclerostomies. Although topical fluorouracil appears to delay bleb scarring, the corneal findings suggest that it may be more toxic than subconjunctival fluorouracil.

Administration, Topical↗

Rebleeding after traumatic hyphema.

We reviewed the medical records of 175 patients who were admitted between 1977 and 1984 with a diagnosis of traumatic hyphema to define the incidence of operative intervention for the treatment of complications related to rebleeding. Of the 156 patients admitted with primary hyphemas, 25 (16%) rebled during hospitalization. Seven of these 25 in-hospital rebleeds required surgical intervention. Nineteen other patients were admitted with ocular histories and examinations strongly suggestive of rebleeding prior to admission (secondary hyphema--presumed preadmission rebleed). Seven of these 19 eyes underwent surgery. Of the 175 eyes studied, only one eye that did not rebleed underwent surgery during the initial hospitalization. Fourteen (32%) of 44 eyes that rebled underwent operative intervention. Nine of these 14 patients were operated on under general anesthesia. Potential benefits of newer hyphema treatments, such as epsilon-aminocaproic acid, designed to prevent rebleeding should be weighed against not only the ocular risks of rebleeding but also the risks of general anesthesia.

Adolescent↗

Neodymium-YAG laser posterior capsulotomy. Central corneal endothelial cell density.

We determined central corneal endothelial cell densities in 39 eyes in a masked fashion before and after Q-switched neodymium-YAG laser posterior capsulotomy. The mean preoperative endothelial cell count was 1,840 cells per square millimeter (SD, 611 cells per square millimeter; range, 522 to 2,742 cells per square millimeter). The mean postoperative endothelial cell count was 1,798 cells per square millimeter (SD, 600 cells per square millimeter; range, 478 to 2,750 cells per square millimeter). The difference between the mean preoperative and postoperative cell density was 42 cells per square millimeter (2.3% cell loss). There was no significant correlation between central corneal endothelial cell loss and the laser energy used, pseudophakic status (posterior chamber intraocular lens vs no intraocular lens), size of capsulotomy, vitreocorneal touch, or preoperative corneal endothelial cell density.

Cataract Extraction↗

Wound healing after filtering surgery in owl monkeys.

We performed posterior lip sclerectomies in 29 owl monkey eyes to determine the natural history of wound healing after filtering surgery without adjunctive antimetabolite therapy. We noted three phases of wound healing during clinical and histologic examination: early healing (days 2 to 6), intermediate healing (days 7 to 9), and late healing (days 10 to 14). In the early healing phase, all limbal fistulas except one remained open gonioscopically, but by day 6, fibroblasts had proliferated along the walls of the opening. Proliferation and migration of fibroblasts continued during the intermediate healing phase to completely occlude four and to partially occlude two of the ten fistulas in the eyes studied during this time. In the late healing phase, the limbal fistula was completely closed by granulation tissue in four of five eyes and was slitlike open in one eye. In this model of filtering surgery, wound healing at the sclerectomy site with obliteration of the limbal opening by proliferating fibroblasts occurred within the first 14 postoperative days. We believe that the short-term effects of newer treatments designed to alter wound healing after filtering surgery may be assessed in this model, which is characterized by predictable and prompt wound healing.

Animals↗

5-Fluorouracil and glaucoma filtering surgery. III. Intermediate follow-up of a pilot study.

Ninety-five patients (104 eyes) were enrolled in a pilot study of subconjunctival 5-fluorouracil (5-FU) injections after filtering surgery in eyes with poor surgical prognoses. At least a six-month follow-up was available on 84 patients, of whom four were excluded from the analysis of surgical outcome because they suffered retinal detachments within six months of their filtering surgery. The initial 5-FU procedures on the remaining 80 patients were successful (no further glaucoma surgical procedures were either performed or recommended, and the intraocular pressures [IOPs] were either 21 mmHg or lower with ocular hypotensive medication[s] or 25 mmHg or lower without ocular hypotensive medication) in 33 (68%) of the 48 aphakic eyes with non-neovascular glaucomas, 13 (81%) of the 16 phakic eyes with non-neovascular glaucomas after unsuccessful filtering surgery, and 12 (75%) of the 16 eyes with neovascular glaucoma (NVG). The follow-up on the successful eyes ranged from 6 to 34 months (mean +/- SD = 18.5 +/- 7.5). The visual acuities remained within one line of their preoperative levels or improved in 38 (79%) of the 48 aphakic eyes with non-neovascular glaucoma, 11 (69%) of the 16 phakic eyes with non-neovascular glaucoma after unsuccessful filtering surgery, and 12 (75%) of the 16 eyes with NVG. The initial 5-FU procedures on the 104 eyes were complicated by the following: corneal epithelial defects (50%); conjunctival wound and suture tract leaks (36%; 2% underwent surgical repair); suprachoroidal hemorrhages (9%); retinal detachments (3%); subepithelial corneal scarring (3%); endophthalmitis (2%); and malignant glaucoma (1%). It is the authors' impression that postoperative subconjunctival 5-FU increases the likelihood of achieving IOP control after filtering surgery in eyes with poor surgical prognoses; however, a randomized clinical trial is necessary to confirm this impression.

Aphakia↗

Visual acuity prediction before neodymium-YAG laser posterior capsulotomy.

A laser interferometer (Retinometer) and the Potential Acuity Meter (PAM) was used to assess macular function before neodymium-YAG laser posterior capsulotomy in 40 patients. Although specificity was excellent with the PAM (91%) and Retinometer (93%), sensitivity was limited to 42% and 33%, respectively. Diffuse posterior capsular opacification which precluded the delivery of light through a clear portion of the capsule was the most likely cause of the high false negative rate. A positive result on either test has good predictive value, reducing the changes of the capsulotomy being a failure by fourfold.

Evaluation Studies as Topic↗

In vitro inhibition of ocular cell proliferation with ara-C: blockage of the antiproliferative effect with 2'-deoxycytidine.

Cytosine arabinoside (ara-C), a cell cycle-phase specific antimetabolite, was tested in a tissue culture model of human scleral fibroblasts (HSCF), and human retinal pigmented epithelium cells (HRPE), to investigate possible applications in the modulation of wound healing after glaucoma filtering surgery and in the postoperative management of proliferative vitreoretinopathy. Cell proliferation after a 72 hr incubation in the presence of ara-C was inhibited to 50% of the control growth rate (ID50) with calculated doses of 60 ng/ml in HSCF and 4 and 5 ng/ml in HRPE cultures. 2'-deoxycytidine, a competitive inhibitor of ara-C action, completely eliminated the cell growth retardation of both cell types produced by ara-C after 72 hr incubation.

Cell Division↗

Glare measurements before and after neodymium-YAG laser posterior capsulotomy.

We measured glare produced by opacified posterior capsules before and after neodymium-YAG laser posterior capsulotomy. In many eyes, particularly those with visual acuities of 20/200 or worse, glare threshold could not be determined. In 32 eyes with measurable preoperative glare, the median glare threshold improved from 45% to 12% and median visual acuity improved from 20/60 to 20/25. For 56 eyes the median postoperative glare threshold was also 12% and the median visual acuity improved from 20/80 to 20/25. Forty eyes achieved postoperative visual acuities of 20/25 or better, but in 16 eyes other ocular conditions limited visual acuity to 20/30 or worse. Glare and visual acuity were correlated preoperatively and usually improved concomitantly. One patient in whom wrinkles in a clear capsule produced streaks around bright lights had a glare threshold lower than other types of opacities. Capsulotomy improved the glare threshold and relieved the symptoms.

Adolescent↗

Topical fluorouracil. Pharmacokinetics in normal rabbit eyes.

Postoperative subconjunctival fluorouracil injections may be a useful adjunct to standard glaucoma filtering surgery in eyes that are at high risk of failure. Topical administration would be preferable to subconjunctival administration; however, there are no data on the ocular penetration of topically applied fluorouracil. Consequently, we investigated the pharmacokinetics of topically administered fluorouracil labeled with carbon 14 in normal rabbit eyes. One drop (approximately 2.4 mg) of fluorouracil resulted in the following concentrations at 0.5 and six hours, respectively: 17.3 and 0.9 micrograms/g of conjunctiva; 24.3 and 1.3 micrograms/g of cornea; 14.6 and 0.2 micrograms/mL of aqueous; 0.8 and 0.5 microgram/g of lens; 1.1 and 0.3 microgram/g of vitreous; and 0.2 and less than 0.1 microgram/mL of serum. Three drops (approximately 7.2 mg) of fluorouracil resulted in the following concentrations at 0.5 and eight hours, respectively: 589.8 and 1.3 micrograms/g of conjunctiva; 502.9 and 1.8 micrograms/g of cornea; 199.6 and 0.8 micrograms/mL of aqueous; 6.2 and 0.5 micrograms/g of lens; 6.8 and 0.5 micrograms/g of vitreous; and 1.3 and 0.2 microgram/mL of serum. Since a fluorouracil concentration of 0.2 microgram/mL inhibits rabbit conjunctival fibroblast proliferation in cell culture by 50%, these data suggest that topically applied fluorouracil achieves sufficient levels in the ocular compartments and tissues to have potential therapeutic applications.

Administration, Topical↗