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Biomedical subjects

J H Lass

Publications and source records attributed to J H Lass.

At least 73 records · Page 4Linked to original sources

An in vitro study of ophthalmic antiviral agent toxicity on rabbit corneal epithelium.

Using an in vitro system we measured the corneal epithelial cytotoxicity and the antiviral activity of the antiviral agents idoxuridine (IDU), trifluridine (TFT), ethyldeoxyuridine (EDU), and (E)-5-(2-Bromovinyl)-2'-deoxyuridine (BVDU). Confluent rabbit corneal epithelial cell cultures were established, and the antiviral agents were added for 5, 30, or 60 min at a range of concentrations including that used clinically (IDU 0.1%, TFT 1.0%, BVDU 0.1%, EDU 2.0%). Twelve hour [3H]thymidine incorporation then was measured and expressed as % inhibition of control cultures. In separate experiments confluent corneal epithelial cell monolayers were inoculated with 10(4) plaque forming units (PFU) of HSV type 1 (McKrae strain) for 1 h, and IDU 0.1%, TFT 1.0%, and BVDU 0.1% were added to the culture for determination of PFU inhibition. Significant dose-, but not time-dependent, toxicity was observed at the clinical concentrations of IDU, TFT, and EDU. Toxicity was absent for BVDU. TFT and IDU were the most toxic, and EDU was of intermediate toxicity. IDU, TFT, and BVDU showed significant antiviral activity in this corneal epithelial cell culture system (TFT greater than BVDU greater than IDU). The results of this in vitro study paralleled the findings of previous in vivo corneal epithelial toxicity studies of IDU, TFT, and BVDU. Our data, however, suggest that EDU has a potential for clinical toxicity and further studies are recommended. Our model may be useful in the future toxicologic study of new antiviral agents.

Animals↗

pH of organ-culture-stored corneas.

Changes in intracorneal and storage-medium pH values of organ-culture-stored cat corneas were monitored over a 4-week period. The intracorneal pH was determined using the phosphorus-31 magnetic resonance spectroscopy (31P MRS) chemical shift of inorganic orthophosphate in conjunction with a standard pH titration curve. We incubated 32 adult cat corneas using two similar standard organ-culture methods, one with chondroitin sulfate (method 1) and the other without (method 2). Time-course data at 0, 1, 3 and 4 weeks of storage were used to calculate the rate of pH change. The intracorneal pH was not changed significantly for either organ-culture method; however, the storage-medium pH rate of change declined significantly for both methods (method 1, 0.15 pH units/week; method 2, 0.12 pH units/week). The difference between intracorneal and storage-medium pH values over time increased at a rate of 0.12 and 0.11 pH units/week for method 1 and method 2, respectively. The declining storage-medium pH in conjunction with the maintenance of intracorneal pH contributes to an increased metabolic demand on the cornea.

Animals↗

Effects of moist-chamber and McCarey-Kaufman medium storage on the metabolic status of the cornea: a 31P-magnetic resonance analysis.

The rate of change in concentration of corneal phosphatic metabolites of cat corneas stored in moist chamber and McCarey-Kaufman (M-K) medium was determined in order to provide a basis for prediction of the corneal metabolic status at a given storage time. Perchloric acid corneal extracts were examined by phosphorus-31 magnetic resonance after storage at 4 degrees C of whole globes under moist-chamber conditions up to 48 h and of excised corneas in M-K medium up to 168 h. A significant decline in the corneal concentrations of ATP and a significant increase in inorganic phosphate occurred for both storage methods; however, depending on the metabolite, the rate of decline or increase was significantly greater for the moist-chamber-stored corneas. The phosphorylated sugars significantly increased and the glycerophosphodiesters significantly decreased in the moist-chamber-stored corneas, whereas both metabolites remained unchanged in the M-K-medium-stored corneas. There was no significant change in the dinucleotides and nucleoside diphospho-sugars during the time course for both storage methods. A threefold greater rate of decline was noted in the tissue energy modulus for the moist-chamber-stored corneas than for the M-K-medium-stored corneas (-0.0465 vs. -0.0121 modulus values/h). M-K medium was significantly more effective in the maintenance of high-energy phosphatic metabolites. The mathematical model for these rate determinations provides a basis for prediction of the corneal metabolic status at a given time in moist-chamber or M-K medium storage.

Adenosine Triphosphate↗

Comparison of the prophylactic effects of 2-deoxycytidine and prednisolone for high-dose intravenous cytarabine-induced keratitis.

In a double-masked, randomized fashion, 11 patients with hematologic malignancies received 13 courses of high-dose cytarabine therapy, intravenously (3 g/m2 every 12 hours for five to six days). Each patient received topical prednisolone phosphate 1% in one eye and 2-deoxycytidine 100 microM in the other eye every six hours. Topical therapy was initiated 12 hours before the first cytarabine dose and continued for up to ten days (until four to five days after completion of cytarabine therapy). Slit-lamp biomicroscopy was performed before therapy and then weekly for one month. 2-Deoxycytidine was equally as effective as the topical corticosteroid therapy in reducing photophobia and pain, microcysts, and punctate epithelial erosions, and each treatment gave results significantly better when compared historically to placebo-treated eyes.

Administration, Topical↗

Interferon-alpha therapy of recurrent conjunctival papillomas.

Five patients with multiple, recurrent conjunctival papillomas underwent surgical excision of their tumor and then received interferon alpha-N1, 5 X 10(6) units/m2 (5 Mu/m2), intramuscularly daily for one month. A similar dose was given two to three times per week for the next six months and tapered off or discontinued thereafter. The follow-up period varied from one to four years. Two patients have had no recurrence of tumor. The other three patients have had recurrences of lesser severity upon tapering or discontinuing the interferon, and repeat surgical or laser excision of these lesions has been performed. The presence of koilocytosis and human papillomavirus type 11a DNA sequences was noted in all specimens large enough to examine, whereas papillomavirus structural antigens were detected in only two of five specimens. A regimen of interferon therapy appears to be tumor suppressive, but not curative.

Adult↗

Comparison of collagen degradation and synthesis in the peripheral and central areas of experimental corneal grafts.

The distribution of collagen degradation and synthesis (turnover) between the central and peripheral areas of clear corneal allografts was determined, following transplantation of 6-mm [3H]proline-labelled corneal buttons from extensively pre-labelled, young rabbits into 13 nonradioactive mature rabbits. Control, contralateral 6-mm corneal buttons of each radioactive pair were frozen at -70 degrees C after being trephined into a central 3-mm button and a peripheral ring of cornea. The grafts were removed 10-100 days after the operation and trephined similarly to the paired controls. The central and peripheral areas of the graft and control corneal buttons were analysed separately for total hydroxyproline and radioactivity. A significant degradation of old collagen (as seen by the loss of total radioactivity) occurred early in both the central (19.4 +/- 6.1%) and peripheral (12.3 +/- 7.5%) areas of the grafted corneas, compared to the corresponding areas of the contralateral controls. A significant increase in new, non-radioactive collagen occurred in both the central (22.0 +/- 7.6%) and peripheral areas (30.6 +/- 6.1%); however, a significant net increase in total collagen occurred only in the peripheral area (18.3 +/- 11.4). Loss of original (old) collagen was significantly greater in the central area than in the peripheral area; whereas, the increase in new collagen was significantly greater in the peripheral area than the central area, accounting for a significant increase in total collagen. There was no correlation in collagen turnover with time after surgery. Collagen turnover occurs acutely throughout the clear corneal graft and thereafter is stable.

Animals↗

Epikeratoplasty. The surgical correction of aphakia, myopia, and keratoconus.

Thirty-five patients have had 39 consecutive epikeratoplasty procedures (12 adult aphakic, 9 pediatric aphakic, 12 myopic, and 6 keratoconic eyes) by the same surgeon, using commercially prepared lenticules. The lenticule remained totally clear in 85% of eyes. Two lenticules were removed due to infection and scarring; four lenticules had minimal scarring and did not require removal. Spectacle-corrected acuity was worse than one line from the preoperative spectacle-corrected acuity in 58% of the adult aphakic eyes; however, 75% were 20/50 or better postoperatively. Fifty percent were within 2 diopters (D) of emmetropia and 92% within 3 D. All pediatric aphakic patients showed an improvement in best-corrected acuity, and 83% of eyes at 6 months were within 2 D of emmetropia; by 1 year a 3.4-D average myopic shift had occurred. Two of the six eyes (33%) using the original myopia technique were within 2 D of emmetropia, whereas five of the six eyes (83%) with the current technique are within this range. Spectacle-corrected acuity in the entire current myopia group has either improved by one or more lines or has remained unchanged. Five of the six keratoconic eyes had 20/40 or better spectacle-corrected and 20/25 contact lens-corrected acuity postoperatively; average corneal flattening was 6 D. Persistent epithelial defect and irregular astigmatism were the principal factors in delay in visual recovery.

Adolescent↗

Preoperative metabolic analysis of donor corneas using magnetic resonance spectroscopy.

Successful corneal transplantation was accomplished following metabolic phosphorus magnetic resonance analysis. Four cat corneas were analyzed using phosphorus-31 magnetic resonance following storage in modified McCarey-Kaufman (M-K) medium for 24 h. Corneas were re-stored in M-K medium and transplanted 24 h after MR analysis. Four control corneas (contralateral eye, no magnetic resonance analysis performed) were also transplanted following storage in M-K medium under identical conditions. Successful corneal transplantation was accomplished with minimal ATP tissue levels. Corneas stored for 48 h maintained a pH of 7.3. The phosphorus-31 spectral modulus, which is the ratio of the high-energy phosphates to the low-energy phosphates, was calculated using the spectral integral (range, 0.49-0.77). No difference in endothelial cell density or morphology was detected between corneas following magnetic resonance analysis and control corneas when evaluated by specular microscopy.

Animals↗

Collagen degradation and synthesis in experimental corneal grafts.

Thirty-two weanling New Zealand white rabbits were labelled repeatedly with [2,3-3-H]-proline for 4 weeks. Four weeks after the end of labelling, 32 rabbits underwent bilateral 6 mm trephinations for donor purposes. One control cornea of each pair was frozen at -70 degrees C. The contralateral corneas were used for autografts, allografts, and xenografts. Grafts were observed from 7-200 days, then retrephined out for determination of loss in total radioactivity in hydroxyproline (specific for collagen), increase in newly synthesized collagen, and net change in collagen mass, by comparing with the matched, ungrafted control corneas. For all three transplant groups there was a small, but significant, decrease early in total radioactivity (loss of original collagen) and a significant increase in new collagen. These data also indicated that the loss of original collagen was replaced by an equivalent or greater increase in new collagen in all transplant groups. Significant relationships between graft clarity and collagen turnover were noted in both the auto- and allograft groups. The degradation of old collagen was significantly greater in the cloudy vs. the clear grafts; however, there was no significant difference in the increase in new collagen between these groups. A progressive loss of original collagen over time was noted in the cloudy autografts, but not the allografts. A trend toward a progressive increase in new collagen was noted over time in both the cloudy auto- and allografts. No relation for these variables to time, however, was noted in the clear grafts.

Animals↗

A morphologic and fluorophotometric analysis of the corneal endothelium in type I diabetes mellitus and cystic fibrosis.

Seven patients with type I diabetes mellitus (Group 1), seven with normoglycemic cystic fibrosis (Group 2), seven with hyperglycemic cystic fibrosis (Group 3), and ten age-matched control subjects underwent corneal fluorophotometry and quantitative specular microscopy. Group 1 had background microangiopathic retinopathy but no evidence of proliferative disease by fluorescein angiography. Significant increases in mean corneal endothelial permeability and mean pump rate occurred in Group 1, indicating a defect in the endothelial barrier function early in type I diabetes mellitus. Similar significant increases in mean corneal endothelial permeability and mean pump rate occurred in both cystic fibrosis groups. The greatest increase was found in Group 3, suggesting a primary defect in the endothelial barrier function in cystic fibrosis, aggravated by the hyperglycemic state. No morphologic abnormalities were noted in Group 1, but both cystic fibrosis groups had smaller mean cell areas than did the control group. There were significant differences in the morphologic and functional correlations between Groups 1 and 3, suggesting different mechanisms for the increased endothelial permeability in these two disorders.

Adult↗

Levobunolol compared with timolol for the long-term control of elevated intraocular pressure.

Levobunolol hydrochloride (0.5% and 1%) and timolol maleate (0.5%) are being compared in an ongoing, double-masked, randomized study of 141 patients with ocular hypertension or chronic open-angle glaucoma. Baseline intraocular pressure (IOP) in the three treatment groups ranged from 26 to 27 mm Hg. During the first 15 months of the study, the two drugs have not proved to be significantly different in ocular hypotensive efficacy, with overall mean IOP decreases of 6.8 to 7.6 mm Hg. In addition, the two concentrations of levobunolol have been equally effective in controlling IOP. Neither drug has been associated with any significant ocular side effects. Both drugs have produced significant decreases (five to ten beats per minute) in mean heart rate. The effect on mean blood pressure has been less pronounced: overall decreases have been less than 4 mm Hg for both systolic and diastolic blood pressure. The results of this ongoing study suggest that levobunolol is as effective and as safe as timolol for the long-term control of IOP.

Adult↗

Childhood orbital pseudotumor.

Pseudotumor of the orbit is an uncommon entity in children. Three patients under 20 years of age with biopsy-proved orbital pseudotumor are presented. A three-month-old infant, to our knowledge the youngest patient reported with orbital pseudotumor, had a history similar to those of previously reported cases, whereas the two older patients differed from previously reported cases of childhood pseudotumor in that they lacked constitutional symptoms and orbital pain. Two of the patients were successfully treated with systemic steroids. In one patient, radiation therapy was required to reduce the mass.

Adolescent↗

Ex vivo metabolic analysis of eye bank corneas using phosphorus nuclear magnetic resonance.

Application of nondestructive and noninvasive nuclear magnetic resonance (NMR) techniques to the evaluation of corneal donor tissue metabolism may provide information that would allow improved selection of donor material for keratoplasty. A phosphorus 31 NMR spectrum was generated from a single intact human cornea, evaluating phosphatic metabolites qualitatively and quantitatively. The NMR analyses were conducted on four corneas (from patients aged from 73 to 75 years). Intracorneal pH (7.2) was monitored from the resonance shift position of inorganic orthophosphate (Pi). A numerical index (1.15) of tissue energy status was determined by comparing the relative tissue content of high-field, high-energy phosphate signals (adenosine triphosphate, adenosine diphosphate, nicotinamide-adenine dinucleotide, and the uridine diphospho-hexoses) to that of the low-field, low-energy phosphate signals (Pi, sugar phosphates, and phosphodiesters). This is the first demonstration of the feasibility of using nondestructive 31P NMR to monitor the metabolic status of a single intact eye bank cornea as would be required in the evaluation of eye bank tissue before keratoplastic procedures.

Adenosine Diphosphate↗

Metabolic status of fresh v eye-bank-processed corneas. A phosphorus nuclear magnetic resonance study.

The concentrations of corneal phosphatic metabolites in fresh and eye-bank-processed corneas were measured by phosphorus 31 nuclear magnetic resonance of perchloric acid corneal extracts to determine whether metabolic differences exist between these two corneal preparations. Cat corneas were prepared using an eye-bank protocol, including specular microscopic examination and transport to a distant location. Fresh cat corneas were used as controls. The hexose 6-phosphate resonance band, the nucleoside monophosphate band, the phosphodiesters, and adenosine triphosphate of eye-bank-processed corneas were significantly decreased relative to fresh control corneas. Phosphatic metabolites that significantly increased relative to control corneas included inorganic orthophosphate and phosphocreatine. A calculated corneal tissue-energy index was significantly decreased for eye-bank-processed corneas relative to control. This decline demonstrates a compromise in the metabolic energy status of the tissue and is indicative of a diminished ability of the cornea to maintain its complement of high-energy phosphates.

Adenosine Triphosphate↗

Antiviral medications and corneal wound healing.

Masked controlled rabbit studies were done to determine the toxic effects on corneal wound healing of the antiviral ointments 0.5% idoxuridine, 3% Ara A, and 3% acyclovir, and the antiviral drops 0.1% idoxuridine, 3% Ara AMP, and 1% trifluridine. Ara A, acyclovir, trifluridine and idoxuridine drops had no significant effects on the rate of closure of epithelial wounds. Idoxuridine ointment given 5 times a day significantly retarded the rate of epithelial wound closure, but not when given 4 times a day. Only Ara AMP caused a retardation of epithelial healing and an actual increase in the defect after 4 days of treatment. Histopathologically all drugs, except acyclovir, showed a toxic effect on the regenerating epithelium. All drugs, except acyclovir, showed retarded stromal wound healing with reduced bursting strength and collagen content. Ara AMP had increased bursting strength and collagen content possibly because of greater inflammation. Acyclovir, in comparison to all the other medications studied, appeared to have minimal to no toxic effects on experimental epithelial and stromal wound healing, and on this basis is the agent of choice for use in herpes simplex stromal keratitis with ulceration and as a prophylactic agent for long-term use after penetrating keratoplasty.

Animals↗

Actinobacillus actinomycetemcomitans endophthalmitis with subacute endocarditis.

Endocarditis and unilateral endophthalmitis due to Actinobacillus actinomycetemcomitans heart disease. The ocular infection was notable for its localized presentation and slow evolution. Treatment with systemic, subconjunctival, and topical gentamicin sulfate and ampicillin sodium achieved 20/20 acuity with a residual chorioretinal scar in the nasal periphery. Intravitreal injection of the organism into a rabbit confirmed its minimal pathogenicity within the eye. This organism must now be considered in patients with differential diagnosis of endogenous endophthalmitis complicating endocarditis and septicemia.

Actinobacillus↗