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Biomedical subjects

H D Cavanagh

Publications and source records attributed to H D Cavanagh.

At least 127 records · Page 7Linked to original sources

Surgical treatment for a case of postoperative Pseudallescheria boydii endophthalmitis.

Pseudallescheria boydii (P. boydii) is an uncommon ocular pathogen which previously has been identified in only 10 of 905 fungal isolates identified by the Sid Richardson Microbiology Laboratory at the Cullen Eye Institute of Baylor College of Medicine. Furthermore, only one case of postoperative P. boydii endophthalmitis and four cases of endogenous P. boydii endophthalmitis have been reported. Three of the four patients with endogenous endophthalmitis died within 4 weeks of diagnosis. We describe a second case of postoperative endophthalmitis due to this fungus. The infection was successfully eradicated following vitrectomy, corneoscleral resection, and patch graft, in addition to intraocular, topical, and oral antifungal medication. Although in vitro sensitivities are variable, P. boydii is known to be relatively resistant to amphotericin B. This points to the importance of proper cultures and sensitivities when treating cases of suspected fungal endophthalmitis. Unfortunately, the patient's eye became phthisical 6 months following the initial intervention.

Aged↗

The magic mountain.

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Corneal Transplantation↗

The molecular basis of neurotrophic keratitis.

Endogenous proliferation of corneal epithelial cells is regulated by a bidirectional control process characterized by an adrenergic, cAMP-dependent 'off', and a cholinergic, muscarinic cGMP-dependent 'on' response. The adrenergic receptor(s) are located in the plasma membrane (microsomal fraction), whereas the novel feature of the system is a cholinergic receptor specific for acetylcholine (ACH) located in the nuclear membrane. Exogenous substances which raise intracellular cAMP levels such as isoproterenol or PGE1, shut off epithelial mitosis: and, carbamylcholine or ACH raise intranuclear cGMP levels and increase mitosis by specific, regulatory stimulation of RNA-polymerase II activity. We believe that this regulatory system explains the transitory mitotic suppression induced by superficial corneal wounding (interruption of adrenergic fibres, chalone-effect); and the marked, permanent depression of epithelial mitosis associated with decreased intracellular ACH levels which are produced by total corneal denervation, and which results in neurotrophic keratitis.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Penetrating keratoplasty in the management of iridocorneal endothelial syndrome.

The clinical results of penetrating keratoplasty for iridocorneal endothelial (ICE) syndrome are presented. Nine cases of penetrating keratoplasty for ICE syndrome were reviewed retrospectively. All grafts remain clear, with posterior corneal changes occurring in only one case, after a mean follow-up of 43 months. Penetrating keratoplasty produced visual improvement in 7 of the 9 cases, relief of pain in 6 of 6 cases, and prevention of further corneal infection in 1 case. We believe that penetrating keratoplasty has a place in the treatment regimen of this disease, not only to achieve improvement in vision, but also for relief of pain, and avoidance of recurrent corneal infections, and to allow a clear media for careful monitoring of optic disc and field changes in the associated glaucoma.

Adult↗

Effect of donor epithelium on corneal transplant survival.

Two hundred thirty-two penetrating keratoplasties in 228 eyes were performed with or without the removal of donor corneal epithelium in a prospective, randomized clinical trial to determine the effect of epithelial removal on graft survival. The removal of epithelium did not reduce the likelihood of graft failure, irreversible allograft reaction, or reversible allograft reaction.

Corneal Transplantation↗

Penetrating keratoplasty for herpes simplex keratitis and keratoconus. Allograft rejection and survival.

To determine the relationship between corneal allograft rejection and failure, we studied patients who underwent penetrating keratoplasty for herpes simplex keratitis (n = 82) and keratoconus (n = 345), two frequent indications for keratoplasty in young patients, using survival analysis. For first grafts for herpes, the probability of survival was significantly less than it was for keratoconus (P less than 0.0001). For second grafts, this difference was less pronounced, and for three or more grafts, the difference in survival was not significant. The incidence of rejection episodes was similar in first grafts for herpes (16.6%) and keratoconus (18.5%) (P greater than 0.05). However, the incidence of rejection episodes in regrafts for herpes was significantly greater than in keratoconus (23.7 versus 17%, P less than 0.01). The incidence of failure after rejection episodes (first grafts and regrafts combined) was significantly greater in grafts for herpes (52.4 versus 16.2%, P less than 0.001). Because survival after multiple regrafts in both groups is poor, additional measures, such as tissue matching, may be necessary to improve the likelihood of success in these high-risk cases.

Adolescent↗

Survival of corneal grafts from donors supported by mechanical ventilation.

Eighty-five patients undergoing penetrating keratoplasty with tissue from donors supported by mechanical ventilation (Ventilator group) were compared to a surgeon- and diagnosis-matched group (Control group). Age at surgery, duration of follow-up, and sex of recipient patients were similar in the two groups. The mean donor age in the Ventilator group (26.4 years) was significantly less than in the Control group (45.8 years, P less than 0.0001). Mean time on the ventilator was 99.4 hours (range, 4 hours to 21 days). Overall graft survival rates in the Ventilator and Control groups were similar (P greater than or equal to 0.72). Time on the ventilator did not affect graft survival. Cultures of corneoscleral donor rims were positive more often in the Ventilator group than in Controls (39.7 versus 23.1%), but the difference was not significant (P = 0.09). Prolonged ventilator time was not associated with a higher rate of positive corneoscleral rim cultures, nor did positive cultures affect graft survival. The most common cause of graft failure in both groups was allograft rejection. In no case could postoperative bacterial infection be attributed to contamination of the donor material. One case of primary donor failure occurred in the Ventilator group, but the incidence (1.2%) is similar to that of previously reported studies. The data indicate that corneal tissue from ventilator-supported donors should be considered for use in penetrating keratoplasty.

Adolescent↗

Activity of DNA and RNA polymerases in resurfacing rabbit corneal epithelium.

Activity of RNA polymerases I, II and III (distinguished using alpha-amanitin) and activity of DNA polymerases alpha and beta (distinguished using N-ethylmaleimide) were assayed for varying intervals and at varying substrate (UTP or dTTP) concentrations in the purified nuclear fraction from corneal epithelium of carbamylcholine-treated and control eyes of rabbits with resurfacing acid burn defects. Incorporation was linear with time for all enzymes up to 30 min. In 10 min assays at varying substrate concentrations, all polymerases from carbamylcholine-treated eyes had significantly elevated Vmax compared to corresponding control enzymes. The drug also increased apparent affinity of RNA polymerase II for UTP and apparent affinity of DNA polymerases alpha and beta for dTTP. Results are discussed in relation to potential mechanisms by which effects of carbamylcholine on polymerase activity may be mediated.

Animals↗

Subcellular localization of muscarinic effects on enzymes of cyclic nucleotide metabolism in cultured corneal epithelial cells of the rabbit.

Activities of adenylate and guanylate cyclases and cAMP and cGMP phosphodiesterases (cAPDE, cGPDE) were assayed in cell homogenates and subcellular fractions of cultured rabbit corneal epithelium, and effects of carbamylcholine on enzyme activities in each fraction were evaluated. Activity of cyclases and phosphodiesterases was detectable in control incubations of homogenates, nuclei, the mitochondrial/lysosomal fraction, microsomes, and cytosol, although microsomal guanylate cyclase represented a very small proportion of the total cellular activity. In homogenates, carbamylcholine significantly elevated guanylate cyclase and cAPDE and reduced cGPDE activity. In mitochondria/lysosomes, guanylate cyclase was elevated and cGPDE reduced, but the drug did not alter cAPDE activity. In microsomes, carbamylcholine enhanced cAPDE but did not alter guanylate cyclase of cGPDE activity. In the soluble cytoplasmic fraction the drug reduced guanylate cyclase activity. The purified nuclear fraction exhibited substantial activity of cyclases and phosphodiesterases. Carbamylcholine significantly elevated activity of nuclear guanylate cyclase and cAPDE and significantly reduced nuclear cGPDE activity. The drug did not significantly alter adenylate cyclase in homogenates or in any cell fraction. The presence of activity of enzymes of cyclic nucleotide metabolism in the cell nucleus and the sensitivity of nuclear guanylate cyclase, cAPDE and cGPDE to carbamylcholine, which in the same concentration range enhances activity of DNA and RNA polymerases, suggested the hypothesis that effects on cyclic nucleotide-dependent phosphorylation of nuclear proteins might be among regulatory mechanisms by which the drug alters rates of replication and transcription in corneal epithelial cells.

3',5'-Cyclic-AMP Phosphodiesterases↗

Effects of topical carbamylcholine on corneal epithelial resurfacing.

Effects of topical carbamylcholine on resurfacing of epithelial defects produced in both eyes of New Zealand albino rabbits with 18 N H2SO4 were evaluated. One eye of each animal received carbamylcholine (50 microliter of a 1.5% solution in HBSS) t.i.d. (10 AM, 1 PM, and 4 PM) for 7 days, with treatment beginning the morning after defect production. The contralateral eye received 50 microliters HBSS and served as control. Resurfacing was monitored by fluorescein staining and photography. Rates of resurfacing were calculated by linear regression analysis of plots of defect surface area versus time. Data represent treated and control eyes of 19 animals in two experimental series. In these experiments, carbamylcholine significantly enhanced epithelial resurfacing, although the effect was not dramatic. Mean resurfacing rates were 11.9 +/- 1.4 mm2/24 hr for carbamylcholine-treated eyes versus 8.5 +/- 1.3 mm2/24 hr for control eyes (p less than .001). On each day after initiation of treatment, the mean percentage of original defect area remaining was significantly lower in treated than in control eyes. At the end of the 7-day treatment regimen, none of the defects were completely resurfaced (mean for treated eyes = 79.9 +/- 2.2%, mean for control eyes = 56.8 +/- 4.3%).

Administration, Topical↗

Gentamicin-resistant Pseudomonas endophthalmitis after penetrating keratoplasty.

A case of pseudomonas endophthalmitis after penetrating keratoplasty is described. Bacterial sensitivities in this case and in five of six previously reported cases of endophthalmitis after corneal transplant showed resistance to gentamicin, an antibiotic routinely used in the transport medium. The recovery of antibiotic resistant bacteria in antibiotic supplemented media is discussed with emphasis on prevention.

Aged↗

Cyclic nucleotides in muscarinic regulation of DNA and RNA polymerase activity in cultured corneal epithelial cells of the rabbit.

DNA and RNA polymerase activities in the purified nuclear fraction from cultured rabbit corneal epithelial cells were assayed over a range of substrate (labeled dTTP or UTP) concentrations using calf thymus DNA as template. Effects of carbamylcholine on polymerase activities were evaluated over a range of drug concentrations including those saturating muscarinic receptors. Carbamylcholine significantly (p less than 0.001) enhanced activity of both polymerases, both in nuclei incubated with the drug during assay and in nuclei from carbamylcholine-treated cells. Drug effects were blocked by atropine. Regression analysis of Hill plots for variation of polymerase activity with carbamylcholine concentration indicated half-maximal activity of both polymerases at approximately 1 microM carbamylcholine. Mechanisms by which carbamylcholine may alter polymerase activities are discussed in relation to effects of the drug on nuclear enzymes of cyclic nucleotide metabolism and on cyclic nucleotide-dependent protein phosphorylation.

Animals↗

Penetrating keratoplasty for exogenous Paecilomyces keratitis followed by postoperative endophthalmitis.

Three patients developed Paecilomyces lilacinus keratitis while being treated with topical corticosteroids and antibiotics. The first patient, a diabetic man, suffered superficial ocular trauma while being treated for recurrent anterior uveitis related to an iris-fixated intraocular lens. The second patient developed keratitis while being treated for anterior segment inflammation associated with herpes zoster ophthalmicus. The third patient, a woman with chronic lymphoma in remission, was receiving topical antibiotics and corticosteroids for a corneal transplant performed one year previously. All three patients underwent penetrating keratoplasty after progression to perforation or failure of medical therapy. Two eyes (cases 1 and 2) eventually required enucleation. The fungal isolates demonstrated in vitro resistance to amphotericin and natamycin with greater sensitivity to imidazole derivatives. Thus, we recommend prompt and prolonged topical treatment with miconazole or other imidazole derivatives along with avoidance of penetrating keratoplasty and corticosteroids.

Aged↗

A cluster of cases of Mycobacterium chelonei keratitis associated with outpatient office procedures.

We studied three cases of keratitis caused by Mycobacterium chelonei, a nontuberculous mycobacterial species. The cases occurred in two women, 76 and 80 years old, and one man, 67 years old, treated as outpatients in the same office. One case followed suture removal and the other two occurred after posterior capsulotomy. Corneal lesions appeared within two to three weeks of trauma and were white, round infiltrates with indistinct margins and radiating projections. The lesions were found at all levels of the stroma and were associated with an epithelial defect. Anterior chamber reaction varied from a minimal response to a hypopyon. One patient responded to topical therapy with amikacin and erythromycin, but the other two patients required penetrating keratoplasties because of deep abscesses, which progressed toward the sclera despite therapy. These cases emphasized the possibility of rapidly growing nontuberculous mycobacteria producing serious ocular infections.

Aged↗