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Biomedical subjects

M J Mannis

Publications and source records attributed to M J Mannis.

At least 55 records · Page 3Linked to original sources

Computerized topographic analysis of the healing graft after penetrating keratoplasty for keratoconus.

After penetrating keratoplasty, visual rehabilitation can be slow and is largely a function of corneal surface configuration. Computerized topographic analysis allows the detailed study of corneal surface factors that determine the optical function of the graft. We performed a prospective, longitudinal study of eight patients with keratoconus by using computerized topographic analysis to determine the rate and pattern of postoperative surface normalization and stabilization. Study data included Snellen visual acuity, contrast sensitivity function, central keratometry, photokeratoscopy, and computerized topographic analysis. Data were collected preoperatively and at one week, one month, two months, three months, and six months postoperatively. Results demonstrate that the greatest configurational changes both topographically and functionally occur in the first month after keratoplasty. The computer-generated surface asymmetry index and the surface regularity index correlated well with improvement in Snellen visual acuity measurements. Contrast sensitivity function was depressed initially but improved to well above preoperative values by one month postoperatively and paralleled the improvement in the surface indices and visual acuity. The axis of astigmatism stabilized by one month postoperatively. Our data indicate that topographic analysis provides a good indication of the rate and course of optical stabilization during the early healing process after keratoplasty and correlates well with visual function in the otherwise normal eye.

Adult↗

Stimulation of epithelial cell growth by the neuropeptide substance P.

The neuropeptide substance P (SP) was found to stimulate DNA synthesis and cell growth for epithelial cells (cornea and lens) in a serum-free environment. The length of treatment time was shown to be important since longer times shifted the dose-response curve to the left. In short-term DNA synthesis studies (40 h) the stimulation with SP (or synergism with insulin) was not apparent until close to 10 microM, however, when DNA synthesis assays were carried out over a long period of time (5 days) stimulation with SP was seen at 1 pM. The stimulation of DNA synthesis by SP was synergistic with insulin for lens epithelial cells, but little synergism was seen with corneal epithelial cells. It cell growth studies on lens epithelial cells SP also showed growth stimulation by itself and synergism with insulin at concentrations of 1-2 pM. The neuropeptide calcitonin gene related peptide (CGRP) showed no DNA synthesis stimulating ability on epithelial cells by itself at concentrations as high as 2.5 microM; however, it was synergistic with SP at a concentration of 0.025 microM. SP pretreatment of epithelial cells for 2 h causes an increase in cellular sensitivity to subsequent addition of either SP or insulin. This increase is consistent with the hypothesis that either the signal from SP persists after its removal from the cell or the dissociation time for SP from its receptor is longer than the wash time.

Animals↗

Defensins are mitogenic for epithelial cells and fibroblasts.

Defensins are a family of structurally homologous peptides contained within phagocytic cells. Although these peptides are best known for their broad spectrum antimicrobial properties, they also inhibit ACTH (corticotropin) stimulated corticosterone production, chemoattract monocytes, and lyse mammalian cells. We now report that these peptides are potent mitogens in vitro in the same concentration range that they display potent antimicrobial activity in vitro. These concentrations are in the same range as those expected to be present in vivo during the wound healing process. All defensins tested were stimulatory for epithelial cells and fibroblasts and acted synergistically with insulin. These are the first data to disclose the strong growth-promoting effects of this unique family of peptides and point to another basic mechanism whereby the macrophage and neutrophil may participate in a variety of trophic, physiologic, and pathologic processes.

Animals↗

Eyelid involvement in acanthosis nigricans.

We treated a 56-year-old man who had acanthosis nigricans associated with gastric adenocarcinoma and involving the axillae, hands, feet, anus, soft palate, and eyes. The patient developed epiphora from occlusion of the canaliculi with papillomatous lesions. Recognition of the ocular signs of this paraneoplastic syndrome may indicate to the ophthalmologist that the patient should have a thorough oncologic examination.

Acanthosis Nigricans↗

Corneal topography of posterior keratoconus.

Posterior keratoconus is an unusual abnormality of the cornea generally classified as one of the anterior chamber cleavage anomalies. It is characterized clinically by the presence of a circumscribed or generalized corneal thinning with posterior depression of the cornea and is considered distinct from keratoconus. Although patients with posterior keratoconus may have visual complaints clearly related to their abnormal corneas, the surface topography of these corneas has not been studied in detail. Keratometry and photokeratoscopy provide an incomplete picture of the surface geometry of posterior keratoconus. We utilized computer assisted topographic analysis to study the cornea of a patient with posterior keratoconus. The Topographic Modeling System demonstrated that the patient's cornea showed a central steepened "cone" coincident with the area of circumscribed posterior keratoconus as well as paracentral flattening. This report documents the topographic abnormality in this rare disorder.

Anterior Chamber↗

The effect of trabeculectomy on corneal topography.

Trabeculectomy is increasingly being performed earlier in the treatment of primary open-angle glaucoma (POAG). Surgically-induced alterations in corneal curvature resulting from filtering surgery may have a significant impact on patients, especially younger ones, whose vision may already be compromised by visual-field loss. Using data obtained by computer-assisted topographic analysis performed preoperatively and at 12 weeks postoperatively, we longitudinally studied the corneal surface changes induced by primary trabeculectomy in eight eyes undergoing surgery for POAG or normal-tension glaucoma. Additional data collected included refraction, keratometry, axial length, intraocular pressure, and pachometry. Five of eight eyes developed 1.50 to 2.50 diopters of steepening in the 90-degree meridian. One patient developed flattening in the 180-degree meridian without vertical steepening. Two patients had little change in the central optical zone. Of the six eyes with induced with-the-rule astigmatism, keratometry was less sensitive than topographic analysis in detecting the changes induced by trabeculectomy. Our data indicate that changes in corneal curvature are induced by filtering surgery, but may be undetectable without topographic analysis.

Astigmatism↗

Myopia and refractive error in dogs.

The refractive error of 240 phakic dogs of various breeds was measured using streak retinoscopy and averaged (-0.27 +/- 1.41 D relative to infinity). Analysis by breed showed that the German Shepherd, Rottweiler, and Miniature Schnauzer breeds had an increased prevalence of myopia with an average refractive error of -0.86 +/- 1.31 D, -1.77 +/- 1.84 D, and -0.66 +/- 1.05 D, respectively. Myopia also was found in older dogs with marked nuclear sclerosis of the crystalline lens. Fifty-three percent of all German Shepherd dogs in a veterinary clinic population (n = 58 eyes) had a myopic refraction of greater than or equal to -0.50 D; 64% of all Rottweiler dogs (n = 28 eyes) were myopic. An in-depth investigation of German Shepherd dogs, using A-scan ultrasonography, photokeratoscopy, and streak retinoscopy, was done at Guide Dogs for the Blind (San Rafael, CA). By contrast with the results obtained in the veterinary clinic population, the overall average refractive error of guide dog German Shepherd dogs (n = 106 eyes) was +0.19 +/- 0.81 D, and only 15% of these dogs were myopic. The axial length and corneal curvature of myopic eyes did not differ significantly from nonmyopic eyes.

Animals↗

Herpes simplex dendritic keratitis after keratoplasty.

We treated three patients with herpes simplex dendritic keratitis that occurred between three and 11 months after keratoplasty. The patients had no history of herpetic infection. The eyes of two of the patients were grafted for corneal scarring of undetermined origin. The eye of the third patient was grafted for pseudophakic bullous keratopathy. At the time of onset of dendritic keratitis, all three patients were receiving either maintenance or higher doses of topical corticosteroids. All infections responded to topical antiviral treatment. The findings in these patients illustrate the importance of considering herpes simplex keratitis in the differential diagnosis of all late-onset epithelial defects in the corneal graft, even in the absence of a history of herpes simplex keratitis.

Administration, Topical↗

In vitro antimicrobial activity of defensins against ocular pathogens.

New approaches to antimicrobial therapy for ocular pathogens must overcome organisms that are resistant to current therapeutic modalities. This investigation examined the antimicrobial activity of novel antimicrobial neutrophil peptides (defensins NP-1 and NP-5) against isolates from clinical ocular microbial infections in humans and horses. The test panel of human clinical isolates included Candida albicans, an alpha-hemolytic Streptococcus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Morganella morganii. The test panel of equine pathogens included three clinical isolates of P aeruginosa and two clinical isolates of Staphylococcus aureus. The equine isolates were chosen for their relative resistance to commonly employed antimicrobial therapy. The two defensins differed markedly in their bactericidal activity. Defensin NP-5, at a 50-micrograms/mL concentration, exhibited minimal bactericidal activity against the majority of isolates of the test panel. The inferior microbicidal activity of NP-5 is consistent with previously published results. However, at this concentration, NP-5 did exhibit appreciable bacteriostatic activity against human ocular pathogens M morganii (74%), alpha-hemolytic Streptococcus (57%), and P aeruginosa (93%) during the 2-hour incubation period. In contrast, defensin NP-1 at 10 micrograms/mL exerted potent microbicidal activity against all isolates, effecting a 2 to 3 log10 decrease in colony-forming units within a 60-minute incubation period. Under the assay conditions employed, these findings demonstrate: (1) two distinct mechanisms by which defensins exert their antimicrobial activity against microbial pathogens associated with clinical ocular disease in humans and horses, and (2) that rabbit defensin NP-1 is a potent antimicrobial agent against a wide array of ocular pathogens.

Animals↗

Intracameral thrombin and the corneal endothelium.

We perfused the endothelia of isolated human corneas mounted in the specular microscope with BSS Plus containing 1,000-U/ml or 100-U/ml dilutions of two commercially available topical thrombin preparations. Corneas perfused with thrombin at 1,000 U/ml showed intracellular and intercellular vacuole formation and altered junctional complexes. As listed on the package inserts, the thrombin preparations contained preservatives and other additives that present a significant osmotic load in 1,000-U/ml preparations. Corneas perfused with 100-U/ml thrombin solutions showed a significant attenuation in their deswelling rate but no ultrastructural alterations. One available thrombin preparation when diluted to 100 U/ml had a glycine concentration associated with previous retinal electroretinography changes. Polyacrylamide gel electrophoresis of one manufacturer's thrombin solution showed multiple high and low molecular weight constituents. Analysis of particulate contamination showed one 100-U/ml thrombin preparation to have a large quantity of particulates. Although thrombin may be useful when applied topically as an aid in surgical hemostasis, its use intraocularly presents substantial concern regarding the preparation's purity, additives, contaminants, and adverse effects on ocular tissues.

Aged↗