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Biomedical subjects

H D Jampel

Publications and source records attributed to H D Jampel.

At least 37 records · Page 2Linked to original sources

A whole-field scotopic retinal sensitivity test for the detection of early glaucoma damage.

We designed and evaluated a new test for the detection of early glaucoma damage in 133 persons who were classified as normal, suspected of having glaucoma, or having glaucoma. The test stimulates the entire visual field with a flashing white light under dark-adapted conditions. It can be performed easily by a high proportion of subjects and is as reproducible as present psychophysical tests. Glaucomatous eyes were discriminated from normal with a diagnostic power of 0.91 as judged by receiver operating characteristic analysis, and specificity and sensitivity were 91% and 86%, respectively. Glaucoma suspects with an abnormal response to the whole-field scotopic test were more likely to have other signs indicating early optic nerve injury, including a greater proportion of borderline field defects, nerve fiber layer defects, or glaucomatous fellow eyes. Assessment of whole-field scotopic sensitivity may be useful in glaucoma screening.

Adult↗

Effect of brief exposure to mitomycin C on viability and proliferation of cultured human Tenon's capsule fibroblasts.

PURPOSE: The purpose of this study is to determine why a single intraoperative dose of mitomycin C (MMC) appears to promote the success of glaucoma filtration surgery. METHODS: Human Tenon's capsule fibroblasts were exposed to MMC and 5-fluorouracil (5-FU) in vitro at the concentrations and durations of exposure used clinically. Cell proliferation was assessed by quantification of 3H-thymidine uptake. Cell viability was studied using a sulfarhodamine B cell protein stain and by trypan blue exclusion. RESULTS: Neither MMC (0.4 mg/ml) nor 5-FU (40 mg/ml) were cytocidal. Both 1- and 5-minute exposures to MMC were antiproliferative. A 1-minute exposure to 0.4 mg/ml inhibited 3H-thymidine uptake by 77%. For the 5-minute exposure, 3H-thymidine uptake was inhibited by 50% at 0.06 mg/ml and by 90% at 0.4 mg/ml. For 5-FU, 3H-thymidine uptake was inhibited by 50% at 10 mg/ml and by 64% at 40 mg/ml. CONCLUSIONS: Mitomycin C probably does not improve the success of filtration surgery by killing fibroblasts. The ability of a brief exposure to MMC to improve filtration surgery may be due to an almost complete inhibition of proliferation. Alternatively, it may be due to sustained tissue binding, effects on other components of wound healing, such as cell migration and extracellular matrix production, or effects on the vasculature. A 1-minute exposure may be as effective as a 5-minute exposure.

Cell Division↗

Effect of topical mitomycin C on glaucoma filtration surgery in monkeys.

In this study, an experimental model of glaucoma filtration surgery was used to evaluate the clinical and histologic effects of a single intraoperative topical application of mitomycin C. Argon laser treatment to the trabecular meshwork produced sustained elevation of intraocular pressure in monkeys. Eight eyes of four animals were randomly assigned to receive topical mitomycin C or balanced salt solution at the time of full-thickness sclerostomy. Surgical success was substantially increased in four of five eyes that received mitomycin C when compared with three eyes that received topical balanced salt solution. Mitomycin C was also effective in prolonging surgical success in two eyes that had previously undergone surgery and failed. No significant ocular toxicity was observed in eyes treated with mitomycin C. Histologic examination of mitomycin C-treated eyes showed patent sclerostomies and hypocellular, well-formed bleb cavities. A single intraoperative application of mitomycin C has a marked effect on postoperative wound healing after filtration surgery in monkeys.

Administration, Topical↗

Effect of paracentesis upon the blood-aqueous barrier of cynomolgus monkeys.

Anterior chamber paracentesis disrupts the blood aqueous barrier (BAB) of rabbits and nonhuman primates, but the magnitude and duration of breakdown in monkeys has not been clarified. We have studied anterior chamber paracentesis in cynomolgus monkeys as a potential model of postoperative BAB breakdown. The effect of a single paracentesis upon fluorescein sodium concentration in the anterior chamber after an intravenous injection was measured in 16 eyes of 8 animals. In an additional 10 eyes of 5 animals, aqueous humor was withdrawn for analysis 24 hours and one week following paracentesis. Anterior chamber fluorescein concentration was 57 +/- 22 ng/ml (mean +/- standard deviation) before paracentesis, rose to 81 +/- 47 ng/ml 24 hrs after paracentesis, and was 60 +/- 36 ng/ml at 72-96 hours. Twenty-four hours after paracentesis, total protein concentration was elevated, but ascorbic acid and transforming growth factor-beta levels were not. Paracentesis in monkeys has only a small and short lasting effect upon BAB integrity and is therefore unlikely to be a good model for assessing the effect of agents designed to stabilize the BAB. However, the short-lived effect of paracentesis may permit the repetitive collection of "primary aqueous" for physiologic and biochemical studies.

Animals↗

Ocular effects of the endothelins. Abundant peptides in the eye.

Endothelins (ETs) are a family of potent vasoactive peptides present in the eye. In the rabbit eye, both ET-1 and ET-3 are present in high concentrations in the iris and ciliary body and in lower concentrations elsewhere. Forty-eight hours after injection of 2.5 micrograms of ET-1 and ET-3 into the anterior vitreous of conscious rabbits, intraocular pressure was reduced by 43% and 45%, respectively, and did not return to normal for at least 5 days. The decrease in intraocular pressure was not due to increased aqueous outflow and was not prevented by pretreatment with indomethacin. Injection of either ET-1 or ET-3 (2.5 to 10 micrograms) into the anterior chamber or posterior vitreous cavity resulted in marked vasoconstriction, which was initiated within seconds and persisted for greater than 4 hours. Both endothelins potently constricted the pupil when added to freshly excised rabbit anterior segments. Endothelins are therefore potential participants in the local regulation of intraocular pressure, ocular blood vessel tone, and iris smooth muscle tone and may be important mediators in ocular pathologic conditions. Endothelins at pharmacologic doses may be useful in the control of intraocular pressure or blood flow.

Animals↗

In vitro release of hydrophobic drugs from polyanhydride disks.

We have evaluated the feasibility of using polyanhydride disks containing hydrophobic antiproliferative agents for controlled drug release after glaucoma filtration surgery. Taxol and VP-16 were the most potent inhibitors of fibroblast proliferation tested, with ID50s of 3 ng/mL and 200 ng/mL, respectively. In vitro release of taxol occurred at concentrations exceeding its ID50 for at least 100 days; VP-16 was released for 31 days. The media into which the drugs were released were able to inhibit fibroblast proliferation in vitro, indicating that the bioactivity of the drugs withstood incorporation into, and release from, the polyanhydride. Polyanhydride disks containing taxol and VP-16 merit testing in animal models of glaucoma filtration surgery.

Alkaloids↗

Transscleral cyclophotocoagulation of human autopsy and monkey eyes.

We studied the effect of uveal pigmentation on contact Nd:YAG transscleral cyclophotocoagulation in 36 human autopsy and eight cynomolgus monkey eyes. Ten autopsy eyes from black individuals required less energy to create a lesion than 23 eyes from whites. The mean lesion diameter at the posterior pars plicata was similar in all these eyes; however, the mean energy required was 4.4 J in the black and 6.4 J in the white eyes. Transscleral cyclophotocoagulation lowered intraocular pressure (IOP) in four monkey eyes with elevated IOP, but did not in four other eyes without elevated IOP. Treatment over conjunctival pigmentation burned the conjunctiva, even at the lowest energy tested (3.5 J). Contrary to other investigators' findings, transmission electron microscopy showed at least short-term loss of scleral architecture in both the human autopsy and monkey eyes.

Animals↗

Trabeculectomy with 5-fluorouracil for adult inflammatory glaucoma.

We reviewed the records of 12 eyes of ten adult patients with inflammatory glaucoma who underwent trabeculectomy with the adjuvant use of 5-fluorouracil between January 1986 and January 1989. Intraocular pressure decreased from 36 +/- 10 mm Hg (range, 17 to 50 mm Hg) preoperatively to 11 +/- 4 mm Hg (range, 3 to 17 mm Hg) postoperatively after a median follow-up of 7.75 months (range, six to 38 months). All eyes achieved an intraocular pressure of less than 20 mm Hg, and ten of 12 required no intraocular pressure lowering medications. The mean (+/- S.D.) amount of 5-fluorouracil used was 33 +/- 10 mg (range, 20 to 55 mg). During the period of observation, five of 12 eyes had an episode of uveitis, but in no patient did this result in loss of intraocular pressure control. Preoperative and postoperative systemic and topical corticosteroid use was the same. Trabeculectomy with 5-fluorouracil is an effective treatment for selected cases of adult inflammatory glaucoma refractory to medical management.

Adult↗

Glaucoma filtration surgery in monkeys using 5-fluorouridine in polyanhydride disks.

We performed filtration surgery in glaucomatous monkeys to determine if bioerodible polyanhydride disks that contained 5-fluorouridine (5-FUR) prolonged the success of the operation. First, in vitro studies demonstrated that 5-fluorouridine was released from the disks for at least 16 days in a bioactive form that inhibited fibroblast proliferation. Next, a preliminary series of six eyes suggested that using disks that contained 5-fluorouridine extended the intraocular pressure-lowering effect of filtration surgery. This finding was confirmed in eight additional eyes of four animals in which one eye received a disk with 5-fluorouridine and the other received a disk without the drug. The duration of success of the operation was significantly longer in the eyes that received polyanhydride with 5-fluorouridine (mean +/- SD, 26.0 +/- 9.2 days) than in the controls (8.5 +/- 4.0 days). The histologic findings of the experimental eyes correlated with their prolonged clinical success.

Animals↗

Topical timolol decreases plasma high-density lipoprotein cholesterol level.

beta-Adrenergic antagonists taken orally adversely alter plasma lipid profiles. This study was designed to determine whether 0.5% topical timolol maleate has a similar effect. Forty volunteers who were not using medications known to alter plasma lipid levels were recruited for an unmasked study in which each subject served as his or her own control. Twelve subjects did not complete the study because of ocular and systemic side effects or extraneous factors. Twenty-eight subjects used topical timolol for an average of 76 days, with two 12-hour fasting plasma specimens obtained at the beginning and end of the period. Mean total cholesterol and low-density lipoprotein cholesterol levels did not change significantly with treatment. Triglyceride values increased 12%; high-density lipoprotein cholesterol levels decreased 9%; and the total cholesterol-high-density lipoprotein cholesterol ratio increased 8%. Higher baseline high-density lipoprotein cholesterol levels were associated with larger reductions in high-density lipoprotein cholesterol levels. Changes in high-density lipoprotein cholesterol levels of this magnitude have been estimated to increase the risk of coronary artery disease by 21%.

Administration, Topical↗

Ascorbic acid is cytotoxic to dividing human Tenon's capsule fibroblasts. A possible contributing factor in glaucoma filtration surgery success.

Successful glaucoma filtration surgery depends on the incomplete healing of the surgical wound, with formation of a filtration bleb. In most other tissues, however, complete healing is the rule. I have explored the possibility that the high concentration of ascorbic acid normally present in aqueous humor inhibits wound healing after filtration surgery. At the concentration normally present in aqueous humor (1.1 mmol/L), ascorbic acid decreased the plating efficiency of cell suspensions of human Tenon's capsule fibroblasts by a mean (+/- SD) of 40% +/- 10%. When added to low-density monolayer cultures of fibroblasts, ascorbic acid decreased the cell number by 90% +/- 5%, an effect that was completely prevented by catalase. When added to confluent cultures, the cell number was decreased by only 14% +/- 2%. If ascorbic acid has similar effects on fibroblasts in vivo, it may contribute to the incomplete wound healing that characterizes successful glaucoma surgery.

Ascorbic Acid↗

Transforming growth factor-beta in human aqueous humor.

The transforming growth factor-beta s are peptide growth factors known to play a central role in wound healing. Using a specific, in vitro assay of cell growth inhibition, we have detected transforming growth factor-beta (TGF-beta) in 24/24 aqueous humor specimens from eyes undergoing cataract extraction with intraocular lens implantation. The amount of TGF-beta ranged from 2.3 to 8.1 ng/ml (mean +/- SD = 4.5 +/- 1.7 ng/ml), with 61% present in the active form. Subtyping of TGF-beta was performed by addition of antibodies specific for the beta 1 and beta 2 isoforms to the growth inhibition assay, and confirmed with a sandwich enzyme-linked immunosorbent assay. None of the TGF-beta detected was of the beta 1 isoform; in contrast, the beta 2 isoform was present in every sample, implying that it might have originated from ocular tissues. The presence of this potent modulator of tissue repair in aqueous humor suggests a role in the healing processes following intraocular surgery, including glaucoma filtration surgery.

Aged↗

Reliability of optic nerve head topographic measurements with computerized image analysis.

We evaluated the reliability of optic disk area and disk rim area measurements obtained with the Humphrey Retinal Analyzer from ten repeat fundus images each of one eye of ten normal subjects and ten subjects with increased intraocular pressure. Variability of rim and disk areas was not significantly different between these two groups (P greater than .05), nor was it significantly different between images acquired during the same session and those acquired during different sessions (P greater than .05). Variability was significantly different between subject groups based on the distinctness of the disk edge and the slope of the cup wall (P less than .01). The average minimum change in the measurements on the same eye that would exceed variability of the technique at the 95% confidence level was 0.20 mm2 and 0.47 mm2 for rim area for the least variable and most variable subject groups based on optic nerve head characteristics, and 0.09 mm2 and 0.32 mm2 for disk area for the corresponding subject groups. Operator input contributed significantly to overall variability. Reliability of rim and disk areas in this study was comparable to that reported for other computerized image analyzers.

Adult↗

Variability of depth measurements of the optic nerve head and peripapillary retina with computerized image analysis.

Computerized topographic mapping of 10 repeated fundus images of one eye each in 10 healthy subjects and in 10 subjects with elevated intraocular pressures (IOPs) was performed with the Humphrey Retinal Analyzer. The variability of depth measurements at 400 to 650 individual locations in the optic nerve head and peripapillary retina was evaluated. The average size of the 95% confidence intervals for individual depth measurements for healthy subjects and those with elevated IOPs were 166 and 232 microns in the optic nerve head and 205 and 261 microns in the peripapillary retina, respectively. Variability was significantly less for healthy subjects than for those with elevated IOPs. Variability was significantly greater for depth measurements in the peripapillary retina than for measurements in the optic head. Knowledge about variability of individual depth measurements is useful for proper interpretation of computerized topographic mapping to detect retinal nerve fiber damage.

Adult↗