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Biomedical subjects

H D Cavanagh

Publications and source records attributed to H D Cavanagh.

At least 163 records · Page 9Linked to original sources

Effect of bilateral and unilateral grafts on the incidence of rejections in keratoconus.

We studied results of 124 keratoplasties in 100 keratoconus patients; 61 men and 39 women varying in ages from 11 to 69 years with an average age of 30 years. Twenty-four patients had bilateral grafts with a 27% incidence of rejection, and 76 patients had unilateral grafts with a 13% incidence of rejection (P less than .01). Data analysis of the first year after the graft of first eyes and subsequent years after the graft of first and second eyes, however, revealed a nearly fourfold increase of rejections following second grafts, with a 17% increased chance of rejection for the first graft after the second was implanted. Only two of the bilateral and two of the unilateral grafts were irreversibly lost because of graft reaction. The major complication was the formation of posterior subcapsular cataract, which occurred in approximately 32% of the patients. The final postkeratoplasty visual acuities were significantly improved. In the patients who did not develop a cataract, 86% achieved visual acuity of 6/12 (20/40) or better. In the patients who did develop cataracts, 68% achieved visual acuity of 6/12 (20/40) or better.

Adolescent↗

Penetrating keratoplasty using McCarey-Kaufman preserved corneal tissue.

Two hundred consecutive penetrating keratoplasties, using suitable donor corneas stored in modified tissue culture medium (M-K medium), were performed by a single surgeon over a 21-month period. Two hundred consecutive cultures of the donor corneosclearl rims for aerobic and anaerobic bacteria and fungi, done immediately after surgery, yielded 25 positive cultures for aerobic and anerobic bacteria and three for fungi. No clinical infections nor primary donor failures were encountered with patients after one to 21 months of follow-up. Preservation of excised corneas by trained technicians, under rigidly sterile, laminar-flow, tissue culture conditions appears to be a convenient, safe, and effective method of corneal preservation which permits elective keratoplasty.

Adolescent↗

Conjunctival resection treatment and ultrastructural histopathology of superior limbic keratoconjunctivitis.

Four patients with symptomatic superior limbic keratoconjunctivitis underwent resection of the superior bulbar conjunctiva. One of these patients also underwent a tarsal conjunctival resection in the other eye. Three of the patients had previously been treated by various regimens without resolution; the fourth had had no prior treatment. All four patients had immediate and continued relief of the ocular symptoms after the superior bulbar conjunctiva was excised. The patient who underwent tarsal conjunctival resection experienced only short-term relief. We studied the conjunctival tissue by light and transmission electron microscopy. Both techniques revealed abnormalities related to the bulbar conjunctival surface with keratinization of the epithelium, acanthosis, degeneration of the nuclei, and intracellular accumulation of glycogen. Inflammatory cells were minimally present. The tarsal conjunctiva appeared essentially normal.

Adult↗

Keratinization of the bulbar conjunctival epithelium in superior limbic keratoconjunctivitis in humans. An electron microscopic study.

A prominent histological feature of superior limbic keratoconjunctivitis is the presence of keratinization of the superior bulbar conjunctiva. Ultrastructurally the affected conjunctival epithelium shows all of the characteristics of keratinization as described in skin. There is a superficial layer of horny cells with reduced organelles and thickened cell membrane. In the intermediate layers, the cells contain an increased number of cytoplasmic filaments which are sometimes aggregated into dense masses, keratohyalin granules, both in the cytoplasm and in the nucleus, membrane coating granules, lysosomes and various other types of membranous structures.

Conjunctiva↗

The fine structure of nuclear changes in superior limbic keratoconjunctivitis.

Superior limbic keratoconjunctivitis (SLK) is a condition of unknown etiology. Histological signs include acanthosis, dyskeratosis, keratinization, and ballon degeneration of the bulbar conjunctival epithelium. Ultrastructural examination of biopsy material from five eyes of patients with SLK shows numerous nuclear changes in the conjunctival epithelial cells. These include abnormal distribution and aggregation of nuclear chromatin, the presence of filaments within the nucleus, and dense accumulations of cytoplasmic filaments which surround the nucleus, resulting in "strangulation" and the formation of multilobed nuclei or multinucleated cells. These changes do not appear to have been described previously in any cell type.

Cell Nucleus↗

Bilateral central lipid infiltrates of the cornea.

A 55-year-old woman developed a skin rash and lipid deposition centrally in previously normal corneas. Despite a family history of coronary artery disease, no serum lipid abnormality was detected. Lipid droplets and granules were deposited throughout the corneal epithelium and stroma. Histochemical stains were positive only for phosopholipid and galactolipid. After a keratoplasty, deposition of similar lipid material recurred in the graft. An inflammatory process and increased corneosceleral limbal vascular permeability may have accounted for the unusual corneal findings in this patient.

Cerebrosides↗

Induced ocular pseudopemphigoid.

Two patients with a clinical picture identical to idiopathic ocular cicatricial pemphigoid had received long-term (six to nine years) echothiophate iodide treatment for control of glaucoma in the affected eyes after cataract extraction. Basement membrane zone staining for IgG was seen in the conjunctiva of one affected eye. Decreased or absent goblet cells, epidermalization of the conjunctiva, fibroses, and abnormal numbers of inflammatory cells were seen in both affected eyes.

Administration, Topical↗

Penetrating keratoplasty in acute herpetic corneal performations.

Central corneal perforations have traditionally been managed by conjunctival flaps, tissue adhesives, soft contact lenses, corneal patches and other conservative measures for the immediate preservation of the eye. An alternative method of treatment is immediate penetrating keratoplasty. We present the result of immediate keratoplasty for 25 eyes referred with acute central corneal perforations, 20 of herpetic origin and 5 with a chemical burn or dry eye syndrome. In all cases, the eye was successfully preserved. Twelve of 20 grafts (60%) for herpetic perforation went on to eventual clear grafts as opposed to 1 of 5 grafts (20%) in the dry eye or chemically burned patients. Significant complications encountered included cataract formation, secondary glaucoma and persistent epithelial defects; however, these should not preclude eventual restoration of good visual acuity. Penetrating keratoplasty in acutely inflamed and perforated eyes used to lead to angle closure and secondary glaucoma in a considerable number of cases, sometimes progressing to total disaster. We have shown that if enough corticosteroids are given immediately postoperatively, the risk for angle closure is not significant.

Administration, Topical↗

Pathology of ocular irritation with bleaching agents in the rabbit low-volume eye test.

Despite differences in the processes leading to tissue damage, the ocular irritation response to various surfactants, two concentrations of an acid and an alkali, and an acetone, alcohol, aromatic amine, and aldehyde has been shown to depend on the extent of initial injury. The purpose of this study was to assess the extent to which this fundamental relationship exists for bleaching agents in the rabbit low-volume eye test. Ten microl of sodium perborate monohydrate (NaBO3), sodium hypochlorite (NaOCl), 10% hydrogen peroxide (H2O2), and 15% H2O2 was applied directly to the cornea of the right eye of each rabbit. Macroscopic assessments for irritation were made 3 hours after dosing and periodically until 35 days. Light microscopic examinations were conducted on tissues obtained at 3 hr and on 1, 3, and 35 days. In vivo confocal microscopy (CM) and measurements of dead corneal epithelial cells and keratocytes at 3 hours and 1 day were used to characterize quantitatively initial corneal injury, while in vivo CM performed at 3 hours and 1, 3, 7, 14, and 35 days was used to characterize quantitatively the corneal changes over time. The changes with NaBO3 and NaOCl were consistent with mild irritancy. For both, corneal injury was limited to the epithelium and superficial stroma. The changes with 10% H202 and 15% H2O2 were consistent with severe irritation. Both concentrations affected the epithelium and deep stroma, with 15% H2O2 also at times affecting the endothelium. However, unlike other irritants previously studied, with 10% H2O2 and 15% H2O2 there was an incongruity between the extent of epithelial and stromal injury, with stromal injury being more extensive than epithelial injury. A similar, although less dramatic, effect was observed with NaBO3. Additionally, there was still significant keratocyte loss at 35 days with 10% H2O2 and 15% H2O2 even though the eyes at times were considered to be macroscopically normal. These observations highlight the need to include both epithelial and stromal components in an ex vivo or in vitro alternative assay. In conclusion, these results continue to support and extend our hypothesis that ocular irritation is principally defined by the extent of initial injury despite clear differences in the means by which irritants cause tissue damage. Importantly, we have identified unique differences in the ocular injury and responses occurring with bleaching agents that are important to consider in the development and validation of alternative ocular irritation tests to characterize a broad range of materials differing in type and irritancy.

Animals↗

Pathology of ocular irritation with acetone, cyclohexanol, parafluoroaniline, and formaldehyde in the rabbit low-volume eye test.

The ocular irritation responses to 11 different surfactants and two concentrations of acetic acid and sodium hydroxide have been shown to depend on the extent of initial injury, despite marked differences in the processes leading to tissue damage. The purpose of these studies was to determine the extent to which this fundamental relationship applies to other nonsurfactants. Ten microl of acetone (ACT). cyclohexanol (CY), parafluoroaniline (PF), or 37% formaldehyde (FA) was directly applied to the cornea of the right eye of each rabbit. Eyes and eyelids were macroscopically scored for signs of irritation beginning 3 hours after dosing and periodically until recovery or 35 days. Tissues were obtained for light microscopic examination after 3 hours and on days 1, 3, and 35. Initial corneal injury was characterized quantitatively at 3 hours and I day using in vivo confocal microscopy (CM) and by postmortem quantitation of dead corneal epithelial cells and keratocytes using a Live Dead Assay (L/D, Molecular Probes) and scanning laser CM. Corneal changes over time were characterized quantitatively using in vivo CM performed at 3 hours and 1, 3, 7, 14, and 35 days. The changes with ACT were consistent with mild irritation. Corneal injury was limited to the epithelium and superficial stroma, with the mean normalized depth of injury (NDI) being less than 10% with the majority of regions showing no stromal injury. Changes with CY and PF were consistent with moderate to severe irritation, and FA caused severe irritation. Specifically, corneal injury by CY and PF tended to involve the epithelium and anterior stroma, with the mean NDI being 10.4% to 23.8%, while injury with FA involved the epithelium, deep stroma, and at times the endothelium. Interestingly, with FA significantly less injury was observed at 3 hours with a dramatic increase in injury observed at 1 day and thereafter. In conclusion, these results continue to support and extend our hypothesis that ocular irritation is principally defined by the extent of initial injury despite clear differences in the means by which irritants cause tissue damage. We believe this approach can be applied to developing alternative assays based on injury to ex vivo eyes or injury to an in vitro corneal equivalent system.

Acetone↗

Effect of cell migration on the maintenance of tension on a collagen matrix.

Although it is known that cells promote structural reorganization of the collagen architecture, how individual cells exert mechanical tension on the matrix is not clearly understood. In the present study we have investigated the mechanical interaction of individual corneal fibroblasts with a collagen matrix using an improved version of our previously described in vitro force-measurement system (Roy, P. et al. Exp. Cell Res. 232:106-117, 1997). The elastic distortion of the collagen matrix exerted by cells was temporally recorded and analyzed using a two-dimensional finite-element model to quantify the forces exerted on the matrix. Time-lapse videomicroscopy of serum-cultured cells on the matrix for up to 6 h revealed that individual fibroblasts generated measurable tension on the matrix during pseudopodial extension and slow retraction. Fast retraction, an event observed during active cell migration, was associated with dramatic release of tension on the matrix. An apparent inverse correlation was observed between cell translocation and maintenance of matrix tension. Additional experiments with cells under serum-free conditions revealed that these cells fail to generate any detectable tension on the matrix despite undergoing filopodial extension and retraction. Since serum-free cells do not form focal adhesions or stress fibers, these experimental data suggest that contractility of nonmotile cells, coupled with strong cell-matrix adhesion, is the most favorable mechanism of generating and maintaining tension on the extracellular matrix.

Adhesiveness↗

Quantitative characterization of acid- and alkali-induced corneal injury in the low-volume eye test.

Defining the extent of initial injury has proven to be a useful basis for differentiating the ocular irritation potential of surfactants; however, the applicability of this method to other types of irritants has not been demonstrated. In the following studies we characterized the extent of corneal injury following exposure to different concentrations of acetic acid and sodium hydroxide (NaOH) in the rabbit low-volume eye test. Groups of rabbits received 3% acetic acid, 10% acetic acid, 2% NaOH, or 8% NaOH and were evaluated in vivo by macroscopic and in vivo confocal microscopic examination and postmortem using a live/dead staining kit and scanning laser confocal microscopic examination. Quantitative assessment of macroscopic scores, corneal surface epithelial cell size, corneal epithelial thickness, corneal thickness, depth of stromal injury, corneal light scattering (confocal microscopy through focusing, CMTF), and number of dead cells was conducted at various times, including the following: at 3 hours and at 1, 3, 7, 14, and 35 days. Based on macroscopic scores, the order of ocular irritancy potential was 3% acetic acid < 2% NaOH < 10% acetic acid < 8% NaOH. Evaluation of the quantitative in vivo and postmortem microscopic live/dead data revealed a slight decrease in epithelial thickness and an increase in dead epithelial cell numbers with 3% acetic acid. With 2% NaOH, significant focal changes in epithelial cell size, epithelial thickness, corneal thickness, and number of dead surface epithelial cells occurred at 3 hours and at 1 day, with injury to only a very small number of corneal stromal keratocytes, despite the presence of epithelial denudation. Changes with 10% acetic acid were similar to those noted with 2% NaOH at 3 hours and 1 day, but these changes were more diffuse and included stromal injury to a depth of 7.2 +/- 9.3% of the corneal thickness, with significant numbers of dead keratocytes. Eight percent NaOH, on the other hand, caused focally extensive injury that averaged 26.3 +/- 18.4% of the corneal thickness at 1 day, with significant light scattering from the cornea, which did not return to normal by 35 days postinjury. Overall, these data indicate that ocular irritation as a result of acetic acid and NaOH was associated with changes similar to those observed with surfactants (ie, slight irritants damage the corneal epithelium, mild and moderate irritants damage the corneal epithelium and anterior stromal cells, and severe irritants damage the corneal epithelium and deep stroma). To our knowledge, this is the first time that the ocular irritation potential for different types of materials (acid/alkali, surfactants) has been shown to be primarily dependent on the initial area and depth of injury.

Acetic Acid↗