Search PubMed⌕ Search

Biomedical subjects

H W Thompson

Publications and source records attributed to H W Thompson.

At least 55 records · Page 3Linked to original sources
PubMed1995

Cold stress-induced recurrences of herpetic keratitis in the squirrel monkey.

PURPOSE: Models of recurrent herpetic keratitis that depend on tissue damage or immunosuppression have been described. The authors report a model that depends only on minimal temperature stress to produce clinical recurrences in a small primate. METHODS: Squirrel monkeys (Saimiri sciureus) infected by the ocular route with the Rodanus strain of herpesvirus type 1 (HSV-1) were exposed to temperatures approximately 5 degrees C lower than the usual ambient temperature for periods as short as 12 hours. RESULTS: The corneas showed more or larger lesions typical of recurrent herpetic keratitis than are usually seen in these animals under normal conditions. Statistical analysis showed that there were significantly higher frequencies of epithelial keratitis at 18 degrees C and 20 degrees C (P < 0.0001). CONCLUSIONS: A minimal temperature change produced significant recurrences in this small animal within a short time. Tissues were not damaged to produce the recurrences. This approach may provide an efficient primate model for rapid testing of drugs to prevent clinical recurrence of ocular herpetic keratitis.

Animals↗
PubMed1994

Collagen-based drug delivery and artificial tears.

For patients with conditions requiring chronic rather than acute therapy, the advantages of collagen shields in providing high and sustained levels of drugs and/or lubricants to the cornea are outweighed by the difficulty of insertion of the shield and the problem of blurred vision. We have developed a delivery system in which collagen pieces suspended in a viscous vehicle can be instilled into the lower forniceal space, thereby simplifying application and reducing blurring of vision. The collagen pieces (Collasomes) can be formulated with various constituents such as antibiotics or cyclosporine, or with chemical alterations such as the inclusion of a lipid (Lacrisomes) for the treatment of dry eyes. In the normal eyes of volunteers, Collasomes hydrated in a solution of sodium fluorescein and suspended in a methylcellulose vehicle as a model for delivery of water-soluble drugs produced fluorescein concentrations 17 to 42 times higher in the cornea and 6 to 8 times higher in the aqueous humor, compared with fluorescein-containing vehicle alone. In a preliminary controlled study, 76% of patients with moderately severe keratoconjunctivitis sicca (KCS) preferred Lacrisomes to the vehicle control because of a more soothing effect and longer duration of comfort. All preparations were well tolerated by all study subjects. Current studies involve improving drug delivery by chemically modifying the collagen molecule to slow diffusion of the drug from the Collasome matrix, as well as varying the amount of cetyl alcohol and combining it with modified collagen in Lacrisomes to maximize comfort in patients with dry eyes.

Adult↗
PubMed1994

Effect of topical beta blockers on corneal epithelial wound healing in the rabbit.

Topical beta adrenergic receptor blocking agents (beta blockers) are among the most frequently prescribed ophthalmic drugs. It has been suggested that some of these agents have a toxic effect on the corneal epithelium. In the present study, four beta blockers in common therapeutic concentrations, as well as their vehicles, were applied to rabbit corneas that had undergone mechanical removal of epithelium from a 6 mm diameter corneal wound. The tested drugs (0.25% timolol, 0.25% levobunolol, 0.25% betaxolol, and 0.3% metipranolol) were found significantly to accelerate wound closure, compared with saline treatment in controls. Eyes treated with two of the vehicles (betaxolol vehicle and metipranolol vehicle) also demonstrated more rapid healing than controls, but the magnitude of the effect was not as great as that seen with the drugs. Only the beta blockers were responsible for wound closure before 60 hours, whereas the saline treated controls and vehicle treated eyes required longer times for wound closure. In this model of wound healing, beta blockers appear to have no deleterious effect on corneal epithelial wound healing.

Administration, Topical↗
PubMed1994

Automated keratoconus screening with corneal topography analysis.

PURPOSE: Although visual inspection of corneal topography maps by trained experts can be powerful, this method is inherently subjective. Quantitative classification methods that can detect and classify abnormal topographic patterns would be useful. An automated system was developed to differentiate keratoconus patterns from other conditions using computer-assisted videokeratoscopy. METHODS: This system combined a classification tree with a linear discriminant function derived from discriminant analysis of eight indices obtained from TMS-1 videokeratoscope data. One hundred corneas with a variety of diagnoses (keratoconus, normal, keratoplasty, epikeratophakia, excimer laser photorefractive keratectomy, radical keratotomy, contact lens-induced warpage, and others) were used for training, and a validation set of 100 additional corneas was used to evaluate the results. RESULTS: In the training set, all 22 cases of clinically diagnosed keratoconus were detected with three-false-positive cases (sensitivity 100%, specificity 96%, and accuracy 97%). With the validation set, 25 out of 28 keratoconus cases were detected with one false-positive case, which was a transplanted cornea (sensitivity 89%, specificity 99%, and accuracy 96%). CONCLUSIONS: This system can be used as a screening procedure to distinguish clinical keratoconus from other corneal topographies. This quantitative classification method may also aid in refining the clinical interpretation of topographic maps.

Cornea↗
PubMed1993

An adjustable double running suture technique for keratoplasty.

In a retrospective analysis, we examined 30 consecutive cases of penetrating keratoplasty in which a double running 10-0/11-0 nylon suture technique was used and the 10-0 suture was adjusted early in the postoperative period to reduce astigmatism. When the response to suture adjustment was inadequate, the presence of the 11-0 suture allowed for early (ten to 18 weeks) removal of the 10-0 suture. Rapid visual recovery (12.3 +/- 0.95 weeks; mean +/- standard error) and low levels of final astigmatism (2.66 +/- 0.24 diopters) were achieved. Visual acuity was 20/20 to 20/40 in 25 of the 28 patients (89%) who were visually rehabilitated. In these 28 patients, visual acuity remained stable for the remainder of the study. All patients had a minimum of six months' follow-up from the time of surgery; mean follow-up was 10.6 +/- 1.70 months.

Adult↗
PubMed1993

Effects of scleral reinforcement on the elongation of growing cat eyes.

OBJECTIVE: We investigated the effect of scleral reinforcement on ocular elongation in the rapidly growing eyes of juvenile cats. METHODS: Bands made from donor sclera or expanded polytetrafluoroethylene were used to reinforce one eye of each animal; contralateral eyes underwent sham surgery. RESULTS: During 5 months of follow-up, normal intraocular pressures implied normal functioning of angle structures. A-scan on the central axis showed no difference in globe lengths. Direct physical measurements of the posterior aspect of the globe at enucleation revealed significant decreases in off-center lengthening where reinforcement was present compared with unreinforced areas in the same eyes and in the contralateral unbanded eyes. Venous beading in fundus photographs of three eyes suggested impairment of venous outflow. CONCLUSIONS: Scleral reinforcement appears to control expansion of the growing cat eye to a limited extent, but the effects on vision and retinal perfusion require further investigation.

Animals↗
PubMed1993

Somatosensory evoked potentials induced by stimulating a variable number of nerve fibers in rat.

Somatosensory evoked potentials (SEPs) were recorded from rat spinal cord (sSEPs) and cerebral cortex (cSEPs). Stimulus sites included either one or both sural nerve branches having different fiber populations (group A), or distal to a lesion of controlled size of the sural nerve made 1 week earlier (group B). In the two groups of animals, amplitudes of SEPs correlated with the quantity of large myelinated nerve fibers. Peak latencies of sSEPs in group A related to the ratio of sizes of transmitting fibers. sSEPs and cSEPs in both groups A and B could be recorded in a reproducible fashion by stimulating sural nerve branches or lesioned nerve trunks containing only 100 or less nerve fibers greater than 4 microns in size. Thus, presence of sSEPs or cSEPs after stimulation distal to a lesion site does not insure that many nerve fibers have continuity with the central nervous system (CNS).

Animals↗
PubMed1993

Topical bupivacaine and proparacaine: a comparison of toxicity, onset of action, and duration of action.

Bupivacaine is a local ocular anesthetic with a long duration of action when administered by retrobulbar injection. To determine the potential for the use of bupivacaine as a topical ocular anesthetic, the onset and duration of action and toxicity of various concentrations of bupivacaine were studied after instillation in rabbit eyes. The onset and duration of action were not significantly different from that of topical 0.5% proparacaine. Increasing the pH of the bupivacaine solution from 5.7 to 6.5 nearly doubled the duration of action, but the increase was not sufficient to be clinically important. Slit lamp biomicroscopic examination and scanning electron microscopy showed that bupivacaine was less toxic to the corneal epithelium than 0.5% proparacaine. Healing after keratectomy was significantly more rapid in eyes treated with 0.75% bupivacaine, compared with eyes treated with 0.5% proparacaine. These results suggest that bupivacaine may be less toxic to the corneal epithelium than proparacaine and could be clinically useful for topical ocular anesthesia, particularly if pharmacologic modifications can increase the duration of anesthesia provided by this drug.

Administration, Topical↗
PubMed1993

Histochemical distribution of carbonic anhydrase in rat and rabbit lacrimal gland.

PURPOSE: The purpose of this study was to examine the histochemical distribution of carbonic anhydrase (CA) in lacrimal glands from rats and rabbits; and to determine if age- and/or sex-related differences exist in the amount and distribution of CA in the rat lacrimal gland. METHODS: Lacrimal glands from young (3-12 wk) and aged (2-2.5 yr), male and female F344 rats and male rabbits were fixed in 1% paraformaldehyde and embedded in glycolmethacrylate. CA histochemistry was performed on 2-microns sections. The distribution of CA activity was determined by morphometric analysis. RESULTS: In rat lacrimal gland, CA activity was distributed in a discontinuous, mosaic fashion among the acinar cells. In tissue from young males and females as well as from aged females, about 10% of the acinar tissue displayed CA activity. Significantly more activity was present in tissue from aged male rats. CA was present in the ductal lumina, suggesting that it is a secretory product of the acinar cells. In rabbits, CA activity was associated with the basolateral membranes of the terminal acinar cells only. CONCLUSIONS: In rat, the presence of CA activity in certain acinar cells and in ductal lumina suggests that CA is actively secreted by the lacrimal gland. An age-related increase in the amount of CA activity in the male glands exists that may be under gender-specific hormonal influences. In the rabbit lacrimal gland, the membrane-associated CA found uniquely with the terminal acinar cells suggests that these cells have special transport functions associated with the primary secretion of lacrimal fluid.

Animals↗
PubMed1992

Vancomycin-enriched corneal storage medium.

Antibiotics in a corneal preservation solution probably have little effect during storage at 4 C, but are effective as the tissue is warmed. The tissue acts as a sponge, soaking up the antibiotic from the solution and releasing it into the eye, where the bactericidal effect is achieved. Currently, high concentrations of gentamicin (relative to the minimal inhibitory concentration) are used in the preserving solution for this purpose. Presumably, proportionately high concentrations of any proposed new antibiotic added to supplement the bactericidal effect of gentamicin, such as the vancomycin used in this study, would be required. However, neither the ability of donor tissue to tolerate high concentrations of vancomycin nor the stability of vancomycin at neutral pH in appropriate storage media has been documented. We evaluated the addition of vancomycin (100 micrograms/ml) to two corneal storage media that contained gentamicin in terms of stability of the antibiotic in solution and the effect on the endothelial cells of donor tissue stored for two weeks at 4 C. Vancomycin was stable in solution at neutral pH (7.2) during the five-month period of the study; the concentration exceeded 90 micrograms/ml for the first five weeks. The endothelial cells from donor tissue stored in the vancomycin-enriched media showed no notable differences from those stored in the same media without vancomycin in terms of cell shape, cell borders, cell swelling, and apical holes. The stability of vancomycin in storage and the absence of endothelial toxicity in vitro support the potential use of this antibiotic as a supplement to gentamicin for the prevention of endophthalmitis in patients receiving corneal transplants.

Aged↗
PubMed1992

Molecular and cellular responses of the corneal epithelium to wound healing.

The corneal epithelium responds rapidly to injury, repairing defects with a layer of cells that covers the denuded corneal surface and prevents infection and loss of vision. After a wound, reorganization of the remaining epithelial cells occurs over several hours, resulting in the formation of a migratory leading edge. However, expression of genes such as c-fos occurs within minutes of wounding. This early expression may be important for directing epithelial reorganization and the later mitotic burst. Our results show that receptors for epidermal growth factor are upregulated in the migratory cell population. Proliferation through a mitotic burst was observed in cells surrounding the original wound margin after 36 hours. The interaction between gene expression and cell surface receptors for growth factors and cell proliferation suggests that wound healing occurs in a complex, but tightly controlled process in the corneal epithelium.

Animals↗
PubMed1992

Effect of growth factors on collagen lattice contraction by human keratocytes.

A three-dimensional gel contraction model was used to evaluate interactions between human keratocytes and different kinds of collagen in the presence or absence of various growth factors. Bovine collagen type I or human placental copolymerized collagen type I/III was used to create the lattices. Normal keratocytes from neonatal, aged, and insulin-dependent diabetic donors, as well as abnormal keratocytes from a donor with macular corneal dystrophy, were cultured. Growth factors included epidermal growth factor (EGF), basic fibroblastic growth factor (FGF), insulin-like growth factor (IGF-I), and platelet-derived growth factor homodimer beta beta (PDGF). Gel area and optical transmittance were determined from computerized measurements. Dose-response experiments (0.01-100 ng/ml) demonstrated that PDGF at 10 ng/ml (P less than 0.005) and EGF at 1 and 10 ng/ml (P less than 0.0001) were the most effective in promoting gel contraction, compared to IGF-I and FGF. Comparison of cell strains revealed different dose-response profiles. Cells from insulin-dependent diabetics and cells from a donor with macular dystrophy contracted lattices more rapidly than cells from normal neonates (P less than 0.0001). Lattices of copolymerized human collagen type III/I demonstrated significantly reduced contraction rates (P less than 0.0001) and increased optical transmittance, compared to bovine collagen type I lattices. Ultrastructural studies revealed that keratocytes extend processes to form a network within the collagen lattice. Specialized intercellular junctional complexes were observed by transmission electron microscopy. This model provides a useful in vitro corneal stroma-equivalent for the study of keratocyte, extracellular matrix, and growth factor interactions.

Adolescent↗
PubMed1992

EGF cell surface receptor quantitation on ocular cells by an immunocytochemical flow cytometry technique.

A method is presented for the rapid flow cytometric determination of epidermal growth factor (EGF) receptor densities on the surface of cultured ocular cells. The technique uses a biotinylated monoclonal antibody directed against the EGF receptor in conjunction with a streptavidin-bound fluorochrome and requires the specific fluorescence per cell to be measured as a function of ligand and receptor concentration. Because the measurement is noninvasive and restricted to cell surface-bound material, the cells can be kept in a physiologic environment, even at the moment of assay. Calculated receptor densities ranged from 5142/cell (infant human corneal endothelium) to 35,678/cell (infant human keratocytes) to greater than 5 x 10(5)/cell for an A431 control cell line. Species and donor age differences were noted, as was transient receptor downregulation after EGF administration. Flow cytometry represents a valuable time saving procedure for large scale applications while providing the same level of sensitivity as standard radioimmunoassays. This technique is applicable to quantitation of other growth factor cell surface receptors and could greatly expand the use of flow cytometry in the research laboratory.

Animals↗
PubMed1991

Optisol corneal storage medium.

Optisol is an investigational, intermediate-term corneal storage medium containing chondroitin sulfate and dextran to enhance corneal dehydration during storage. We used scanning electron microscopy to grade endothelial cell morphologic characteristics in terms of cell shape, cell borders, cell swelling, and apical holes in pairs of corneas stored in Optisol and Dexsol. Optisolstored corneas showed significantly fewer morphologic changes after 14 days at 4 degrees C than did Dexsol-stored corneas. No significant differences were seen after 1 to 4 days at 26 degrees C. Temperature-reversal analysis showed no significant change in corneal thickness with warming after 2-week storage at 4 degrees C in either medium, although Optisol-stored corneas were significantly thinner than those stored in Dexsol at all times. The results of scanning electron microscopy suggest that preservation at refrigerator temperature for 2 weeks in Optisol is superior to preservation in Dexsol. Both media may be useful in preserving endothelial structure for limited periods at room temperature, which could provide a measure of safety in shipping or storage where refrigeration is unreliable.

Adult↗
PubMed1991

Suppression of ocular herpes recurrences by a thymidine kinase inhibitor in squirrel monkeys.

5'-Ethynylthymidine, an inhibitor of viral thymidine kinase (TK), was given intraperitoneally to squirrel monkeys previously infected by the ocular route with Rodanus strain herpes simplex virus. Spontaneous ocular recurrences were reduced during therapy, compared to saline-treated controls. This is the first in vivo demonstration that a viral TK inhibitor can reduce recurrences of HSV-1. Similar benefit would be expected for HSV-2 and perhaps VZV (varicella zoster virus).

Animals↗
PubMed1991

Flow cytometry measurements of the DNA content of corneal epithelial cells during wound healing.

This study presents the first application of flow cytometry (FCM) techniques to the assessment of cell cycle dynamics in the corneal epithelium after experimental wounding. Anterior keratectomies 6 mm in diameter were created in the central corneas of albino rabbits. The authors sampled the epithelial tissue obtained outside the wound at 12-hr intervals until wound closure at 72 hr. Regenerated epithelium from the surface of the wounded area was collected at 78 hr. The percentages of nuclei in the G0/G1 (growth), S (DNA synthesis), and G2/M (tetraploid/mitosis) phases were determined by FCM. An increase in the percentage of nuclei in the G2/M phase at 36 hr was seen, compared with cell populations in samples from unwounded control corneas. The authors found an increase in mitotic activity in the corneal epithelium during the period of cell migration before wound closure.

Animals↗