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Biomedical subjects

K R Kenyon

Publications and source records attributed to K R Kenyon.

At least 127 records · Page 7Linked to original sources

Diffuse drusen and associated complications.

An eye of a patient with an unusual form of diffuse drusen was studied by light and electron microscopy. Examination disclosed marked diffuse and nodular thickening of the inner portion of Bruch's membrane by vesicular and curvilinear membranous profiles and basement membrane-like material that was apparently derived from the retinal pigment epithelium. Deposition of this abnormal material suggests a diffuse abnormality of the retinal pigment epithelium and predisposes to serous detachment of the retinal pigment epithelium, choroidal neovascularization, hemorrhagic detachment of the retinal pigment epithelium, and disciform scarring. The features of this case are similar to previously reported cases of diffuse drusen, but differ in the early age of onset, intensity of changes, and, in part, by the nature of the abnormal material observed.

Basement Membrane↗

Ocular abnormalities in mucolipidosis IV.

Systemic findings in a 23-year-old white man with mucolipidosis type IV included early delayed psychomotor development, mental retardation, and mild facial dysplasia. There was urinary excretion of chondroitin sulfate. Ophthalmologic examination showed corneal haze, pigmentary retinopathy, and severe optic atrophy. Light microscopy showed massively engorged superficial and intermediate epithelial cells of both the cornea and the conjunctiva. By transmission electron microscopy these contained fine granular material consistent with acid mucopolysaccharide and concentric lamellar bodies presumably representing phospholipids. This storage phenomenon was also found in macrophages, plasma cells, ciliary epithelial cells, Schwann cells, retinal ganglion cells, and vascular endothelial cells. Light microscopy also disclosed early cataract formation, marked outer retinal degeneration, and optic atrophy.

Adult↗

Ascorbic acid therapy in a thermal burn model of corneal ulceration in rabbits.

We studied the effect of topical and systemic ascorbic acid on a rabbit model of corneal ulceration produced by thermal burn. Central stromal ulceration occurred in 77% to 100% of eyes in all treatment groups. The rate of ulceration was accelerated in animals treated with systemic ascorbic acid. Ulceration began after 5.80 +/- 2.14 days in control eyes and 2.75 +/- 1.26 days in the eyes of rabbits treated with both topical and systemic ascorbic acid (P less than .02). Subconjunctival ascorbic acid alone did not affect the rate of ulceration (average onset, 6 +/- 1 days). Once ulceration occurred in animals treated with both topical and systemic ascorbic acid, the incidence of perforation and descemetocele formation was increased and that of healing was decreased. The time required for healing was not significantly altered by treatment (9.50 +/- 2.28 days for control eyes vs 5.75 +/- 2.78 days for treated eyes) (P greater than .05).

Animals↗

In situ actin distribution in excised retrolental membranes in retinopathy of prematurity.

Actin, an intracellular contractile protein, is associated with cell movements in both muscle and nonmuscle tissues. Using the fluorescent derivative of the mushroom toxin, phallacidin, which specifically binds to polymerized (filamentous) actin, we demonstrated the distribution of actin in retrolental membranes excised during open-sky vitrectomy from six infants with leukokoria due to retrolental fibroplasia. Actin was detected in ubiquitous linear bundles, which is consistent with the existence of contractile forces. Actin was also concentrated in the cortical cytoplasm of cells, thus outlining the plasma membranes. Transmission electron microscopy has identified many of these cells to be myofibroblastlike in appearance. Myofibroblasts are known to contract like smooth-muscle cells and have been reported as the putative causal factor in the contraction of scars and transvitreal membranes.

Actins↗

Conjunctival autograft transplantation for advanced and recurrent pterygium.

The technique and results of conjunctival autograft transplantation for advanced and recurrent pterygium are presented for 57 eyes of 54 patients. The pterygia were primary in 16 eyes and recurrent in 41; among the latter group, 14 patients had diplopia resulting from cicatricial involvement of the medial rectus muscle. In all cases, free conjunctival grafts from the superotemporal bulbar conjunctiva of the same eye were used to resurface exposed sclera and extraocular muscle. There were no intraoperative complications. Postoperative follow-up ranges from 1 to 67 months, with a mean of 24 months. Only three pterygia have recurred (5.3%); two were successfully remedied by a second conjunctival autograft, whereas the third did not require an additional procedure. In all 14 patients with diplopia, extraocular movement was restored. We recommend this surgical approach as a safe and effective means of treating pterygia complicated by conjunctival scarring with extraocular muscle involvement and requiring concurrent fornix reconstruction.

Adult↗

Topical retinoid treatment for various dry-eye disorders.

We evaluated the clinical efficacy of treating various dry-eye disorders using 0.01% and 0.1% (weight/weight) topical all-trans retinoic acid ointment. Twenty-two patients were selected and classified into four major groups: keratoconjunctivitis sicca (6 patients; 11 eyes), Stevens-Johnson syndrome (9 patients; 17 eyes), ocular pemphigoid or drug-induced pseudopemphigoid (3 patients; 6 eyes), and surgery or radiation-induced dry eye (4 patients; 4 eyes), based on the criterion that they remained symptomatic even under maximum tolerable conventional medical and/or surgical therapies. The results indicated that squamous metaplasia with mucin deficiency secondary to goblet cell loss and keratinization may be the basis for the development of clinical symptoms and morbidities, as these epithelial abnormalities were invariably present before treatment. After treatment, all patients demonstrated clinical improvements in symptoms, visual acuity, rose Bengal staining, or Schirmer test. Most importantly, this topical vitamin A treatment caused the reversal of squamous metaplasia as evidenced by impression cytology. Therefore, this treatment may represent the first nonsurgical attempt to treat these disorders by reversing diseased ocular surface epithelium.

Administration, Topical↗

Tear diluents in the treatment of keratoconjunctivitis sicca.

To determine the optimum solution concentration for lowering elevated tear film osmolarity in keratoconjunctivitis sicca (KCS), tear osmolarity was measured in four KCS patients before and after instillation of either an isotonic saline solution or one of four hypotonic saline solutions (range, 75-225 mOsm/L). Average tear osmolarity one minute after instillation was significantly lower with the hypotonic solutions than with the isotonic saline (mean +/- SEM, 290 +/- 3 mOsm/L vs. 317 +/- 1 mOsm/L, P less than 0.0005). Solutions 150 mOsm/L or less were most effective in lowering osmolarity; the 75 mOsm/L solution was occasionally associated with irritation. In 16 KCS patients, we then compared the therapeutic efficacy of the 150 mOsm/L solution with that of an otherwise identical isotonic solution in a two-week, double-masked, crossover study. The 150 mOsm/L solution was superior for symptom relief by nearly 2:1 (P = 0.01).

Double-Blind Method↗

Tear water evaporation and eye surface diseases.

The water evaporation rate from the tear film of eyes with anterior surface pathology (corneal and/or conjunctival scars, meibomitis) was tested by means of the "Rolando-Refojo tear evaporimeter', which allows noninvasive and reproducible test conditions. These eyes show a statistically significant increase in tear evaporation rate compared to normal eyes. The clinical implications of this finding are discussed.

Adult↗

Cellular migration and morphology in corneal endothelial wound repair.

After a mechanical denudation of rabbit corneal endothelial cells, the healing process was followed with wide-field specular microscopy. Individual cell migration and morphologic changes were analyzed by computer-assisted morphometry. The cells surrounding the wound migrated to cover the defect without producing intercellular gaps. The greatest cellular migration and morphologic alterations occurred close to the wound edge. As the cells migrated toward the wound, they elongated and increased their surface area in the direction of the migration. As the healing proceeded, the cells lost their original hexagonal pattern, which returned after coverage was complete. The wound was covered completely by large, irregularly shaped cells showing mitotic figures between 24 and 48 hr. During this period, cellular migration decreased and normal cellular morphology began to recover. When mitosis decreased, the normal cellular pattern rearranged towards a more hexagonal shape. During the healing process, the degree and direction of cellular migration varied from cell to cell. Additionally, changes in cell-to-cell contact (positional changes of neighboring cells) occurred in one-third of migrating cells. Such cellular migration can account for monolayered cells sliding without producing gaps between individual cells.

Animals↗

A simple vertebrate collagenase assay using soluble radioactive collagen substrate.

A highly sensitive assay for vertebrate collagenase has been developed using [14C]proline- or [3H]proline-labeled collagen as soluble substrate. The substrate was easy to prepare, gave high specific activity (1.4 X 10(6) cpm/mg collagen), and was stable at -20 degrees C for a long period. The digestion reaction for the assay was done at 21 degrees C to minimize the cleavage of collagen by proteases other than collagenase and to protect the 3/4 and 1/4 cleavage fragments of collagen from being further attacked by proteases. The cleaved products were denatured and then separated from undigested native collagen by precipitation with 1 M NaCl at pH 3.5. The conditions selected for denaturation and separation gave better discrimination between the cleaved products and uncleaved substrate than did conditions used in some other assays. The digestion products can be examined further by gel electrophoresis at the end of the assay to confirm the activity of vertebrate collagenase. This assay can also be adapted to assess telopeptidase activity independently of collagenase activity.

Animals↗

Morphologic effect of hyperosmolarity on rabbit corneal epithelium.

The morphologic effect of hyperosmolarity, equivalent to that seen in the tear film of patients with keratoconjunctivitis sicca (KCS), on rabbit corneal epithelium in vitro and in vivo was studied. In the in vitro studies, corneal epithelium was grown in explant cultures. Control tissue was cultured in a 307 mOsm/L medium. Epithelium cultured in the 333, 361 and 363 mOsm/L media showed decreased intercellular connections, blunting and loss of microplicae, disruptions in cell membranes and cellular swelling with decreased cytoplasmic density. In in vivo studies, corneas bathed in balanced salt solutions (BSS) concentrated to 330, 360, or 407 mOsm/L showed increased cell desquamation, and the cell changes observed at similar osmolarities in the in vitro studies. The tear film osmolarities observed in KCS are sufficient to cause the corneal epithelial changes seen in patients with this disease.

Animals↗

Vernal conjunctivitis in the hyperimmunoglobulinemia E syndrome.

Hyper-IgE syndrome (HIE) appears to be related to an immunoregulatory imbalance characterized by severe deficiency of suppressor T cells, elevated levels of IgE antibodies, and repeated infection of various organ systems. We report the association of HIE syndrome in two definite cases and one probable case of vernal conjunctivitis. This association suggests that T cell-mediated imbalance may be one factor in the pathogenesis of vernal conjunctivitis.

Adolescent↗

Possible mechanisms for the loss of goblet cells in mucin-deficient disorders.

By studying the pathological changes in human conjunctival flaps and the conjunctival transdifferentiation in rabbits, we have identified and correlated two pathological processes with the loss of goblet cells: (1) loss of vascularization, and (2) intense inflammation. Loss of vascularization may be correlated with the loss of goblet cells in the chronic cicatricial stage of various mucin-deficient disorders, whereas inflammation may be responsible for their absence in the acute inflammatory stage. The exact interrelationship between these two processes remains unknown. The loss of goblet cells appears to be an early sign of a spectrum of squamous metaplasia, an abnormality of epithelial differentiation. We therefore speculate that loss of vascularization and intense inflammation may have an important effect on epithelial differentiation.

Adult↗

Adverse reactions to virgin silk sutures in cataract surgery.

During the past 3 years, 12 patients (14 eyes) were encountered with severe reactions to virgin silk sutures used in cataract surgery. These reactions included nodular episcleritis, peripheral corneal ulceration, and wound necrosis with dehiscence, sometimes resulting in endophthalmitis or epithelial downgrowth. Conjunctival and scleral histopathologic studies in four eyes showed acute and chronic inflammation with multinucleated giant cells. Successful treatment included removal of the virgin silk sutures, resuturing with 10-0 nylon sutures, securing the necrotic tissue with cyanoacrylate adhesive, and resection of the inflamed superior conjunctiva. All four patients who had bilateral cataract surgery experienced either simultaneous flare-ups of both eyes or accelerated reactions after surgery on the second eye, which suggests a possible role of prior sensitization.

Aged↗

Noninfected corneal ulceration.

The pathogenesis of noninfected corneal ulcers consistently relates to persistent or extensive epithelial defects, concomitant with stromal inflammatory cell infiltration and enzymatic degradation of collagen and ground substance. The therapeutic approaches to these disorders may be considered on three levels: (1) determination of etiology and institution of primary therapy; (2) promotion of epithelial healing; and (3) limitation of ulceration and support of repair. The latter two aspects feature pharmacological management and limited surgical modalities, particularly the use of tissue adhesive.

Adrenal Cortex Hormones↗

Polymorphonuclear neutrophils delay corneal epithelial wound healing in vitro.

Using an in vitro system for measuring epithelial wound healing, we studied the effect of polymorphonuclear neutrophils (PMNs) and PMN lysate on rat corneal epithelial wound healing. After 22 hr of organ culture, epithelial defects that were originally 3 mm in diameter (7.06 mm2) measured 0.41 mm2 (range, 0.17-0.72 mm2) in control rat corneas, 2.11 mm2 (range, 0.81-3.91 mm2) in corneas incubated in medium containing 5 X 10(6) PMN/ml, and 2.49 mm2 (range, 2.21-2.76 mm2) in corneas incubated with lysate obtained from an equivalent number of PMNs. Scanning and transmission electron microscopy showed similar morphology in the three groups. PMNs selectively adhered to the leading edge of the wound in corneas incubated with PMNs. These data indicate that PMNs and PMN lysate significantly slow corneal epithelial wound healing in vitro.

Animals↗