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Biomedical subjects

J P McCulley

Publications and source records attributed to J P McCulley.

At least 19 recordsLinked to original sources
PubMed1998

Keratoconjunctivitis sicca associated with meibomian secretion polar lipid abnormality.

OBJECTIVE: To determine whether an association between keratoconjunctivitis sicca (KCS) and meibomian gland lipids exists in patients with chronic blepharitis. METHODS: Meibomian gland lipids were collected from normal patients and those with chronic blepharitis. Some of the chronic blepharitis patients had an ocular surface abnormality with apparent aqueous deficiency similar to KCS. Lipids were separated by thin-layer chromatography and polar lipids were further separated by high-pressure liquid chromatography with detection by UV absorbance. Lipids were identified by retention time with comparison with standards and by gas chromatography and mass spectroscopy. RESULTS: A strong association between specific lipids and KCS signs was observed only with the polar lipids. Low levels of 2 phospholipids, identified as phosphatidylethanolamine and sphingomyelin, were significantly (P < .05) associated with ocular surface abnormalities that were consistent with KCS. CONCLUSIONS: Evaporative KCS syndrome (rather than tear insufficiency) in many individuals may be the result of polar lipid abnormalities. We believe that the 2 associated phospholipids identified in the patients with chronic blepharitis act as important structural components in the polar phase of the tear film lipid layer. We suggest that a deficiency in these lipids results in a poorly structured polar phase that in turn affects the nonpolar phase. Ultimately water transmission through the tear film lipid layer increases, thus resulting in evaporative KCS. These results should aid in development of tear film substitutes directed toward specific abnormalities.

Blepharitis↗
PubMed1998

Reliability of intraocular pressure measurements after myopic excimer photorefractive keratectomy.

OBJECTIVE: To determine the reliability of intraocular pressure (IOP) measurements by Goldmann applanation tonometry and pneumotonometry in eyes treated with excimer myopic photorefractive keratectomy (PRK). DESIGN: A prospective case series. PARTICIPANTS: Forty consecutive eyes treated with PRK were evaluated. INTERVENTION AND MAIN OUTCOME MEASURES: Central and peripheral corneal Goldmann tonometry and pneumotonometry measurements were done before surgery, at 1 week, and at 1 and 3 months after surgery. RESULTS: The IOP by Goldmann tonometry from the central cornea was significantly lower than the peripheral IOP; however, there was no difference between IOP measured from central and peripheral corneas by pneumotonometry, which, in turn, correlated with peripheral Goldmann measurements. There was a trend, but not a statistically significant correlation, between the spherical equivalent of the treatment and the amount of decrease in central Goldmann IOP. CONCLUSIONS: Pneumotonometry measures the IOP reliably after PRK from all parts of the cornea, whereas central Goldmann tonometry underestimates the IOP by 2.40+/-1.23 mmHg.

Administration, Topical↗
PubMed1997

In vitro amoebicidal activity of propamidine and pentamidine isethionate against Acanthamoeba species and toxicity to corneal tissues.

Effective chemotherapy for Acanthamoeba keratitis has been hampered because of the marked resistance of the parasites to a variety of antimicrobial agents. In view of the fact that topical Brolene (propamidine isethionate) and neosporin are currently considered to be the medical treatment of choice in Europe, we sought to determine whether pentamidine may be equally effective, because the drug is more readily available to ophthalmologists in the United States. In this study, we compared the amoebicidal activity of the Brolene (commercial product), propamidine isethionate and pentamidine isethionate (Pentam) in vitro against three different species of Acanthamoeba, and the drugs' corresponding biocompatibility with rabbit corneal epithelial and endothelial cell cultures. The results indicated that there were significant species differences in drug sensitivity. Propamidine (> 1,000 micrograms/ml) was clearly less effective than pentamidine (> 125 micrograms/ml) against A. castellanii, although equivalent potency (> 250 micrograms/ml) was observed against A. polyphaga. On the other hand, propamidine (> 31.25 micrograms/ml) was slightly more effective than pentamidine (> 62.5 micrograms/ml) against A. hatchetti. Both drugs were also relatively nontoxic after short-term contact with cell cultures, even though the highest concentration of pentamidine caused low-grade injury to the superficial epithelium and reversible membrane damage to the endothelium. Steady-state levels of propamidine at effective amoebicidal concentrations, however, were much more toxic than pentamidine, which indicated that the drug has a much lower therapeutic index. Our data suggest that pentamidine may be an effective therapeutic option because of its potency and low toxicity.

Acanthamoeba↗
PubMed1997

Complications of combined radial thermokeratoplasty and incisional keratotomy.

PURPOSE: To report complications of radial thermokeratoplasty (RTK) when used in combination with either radial keratotomy (RK) or astigmatic keratotomy (AK). METHODS: RTK is a technique for the surgical correction of hyperopia and presbyopia. 600 degrees C burns are applied to the peripheral cornea for 0.3 seconds using a specialized cautery probe. The thermal energy generated shrinks stromal collagen and flattens the peripheral cornea. The central cornea is steepened producing a myopic shift. RESULTS: Two patients who had RTK in combination with either RK or AK are reported. Patient 1 was bilaterally hyperopic and presbyopic. The patient had RTK performed on the left eye in an attempt to make that eye myopic. The goal was to allow the left eye to be used for near vision. After RTK, the left eye was significantly overcorrected. The patient then had RK in the left eye which resulted in profound overcorrection with return of hyperopia. Postoperatively, examination revealed gaping of the RK incisions and poor epithelial wound healing. The patient also complained of severe ocular pain. Despite suturing the RK incisions, the eye remained hyperopic. The patient underwent two additional RTK procedures which failed to correct the induced hyperopia. The second patient had induced hyperopic astigmatism after undergoing RK. RTK was then performed to correct the hyperopia. However, the result was a worsening of the astigmatism. Two t-cut astigmatic keratotomies were then performed which improved the astigmatism but subsequently exacerbated the hyperopia. A second RTK procedure was then performed; however, it failed to correct the induced hyperopia. CONCLUSIONS: RTK is an unproved surgical technique for the correction of hyperopia and presbyopia that needs much further evaluation before broad clinical application can be supported.

Cornea↗
PubMed1997

A compositional based model for the tear film lipid layer.

BACKGROUND: The tear film lipid layer is formed from lipids secreted by meibomian glands of the eyelid. After initial analyses of these lipids we concluded that an understanding of the function of the various classes of lipids in a normal lipid layer could only be understood after detailed investigations of both polar and nonpolar lipids of the meibomian gland. METHODS: Meibomian gland secretions were obtained from normals. Lipids were separated by thin layer chromatography and high pressure liquid chromatography, and analyzed by UV absorbance, gas chromatography and mass spectroscopy. RESULTS: Based on our analyses we concluded that the current understanding of lipid layer composition and function were inadequate or misleading. We therefore propose that the more polar lipids function as a structure (with surfactant characteristics) upon which the functional stability of the more nonpolar lipids are dependent. We further suggest that the interrelationships between lipid classes present, length of fatty acids and alcohols, their unsaturation, and hydroxylation are important for maintaining proper thixotropic characteristics of the lipid layer as well as optimal barrier properties. CONCLUSION: The tear film lipid layer is composed of 2 phases: (1) a thin polar phase adjacent to the aqueous-mucin phase and (2) a thick nonpolar phase associated with both the polar phase and the air interface. The structural characteristics of the polar phase and the barrier functions of the nonpolar phase are a direct result of specific compositional parameters.

Chromatography, Gas↗
PubMed1996

Meibomian gland triglyceride fatty acid differences in chronic blepharitis patients.

In this study, we analyzed the triglyceride fraction of human meibomian gland secretions to determine whether specific fatty acids were significantly associated with specific chronic blepharitis disease groups. Triglycerides, isolated from the lipid component of human meibomian secretions by thin-layer chromatography, were transmethylated with sodium methoxide/methanol. Samples from individuals were then analyzed by gas chromatography-mass spectroscopy (GC-MS). Significant fatty acid differences were determined by nonparametric analyses, utilizing Kruskal-Wallis analysis of between group differences and Student-Newman-Keuls multiple comparisons. The analyses showed that the triglyceride samples contained the expected normal, iso, and anteiso fatty acids; disease group differences (from normals) in some of these fatty acid types were significant only with a Bonferroni adjustment. The triglycerides also contained previously unreported polyunsaturated fatty acids as well as two four-member families of fatty acids that had mass spectra and retention times consistent with dimethylated carbon chains. Additionally, some members of the meibomian keratoconjunctivitis (MKC) group contained an unusual pattern of normal 20-carbon fatty acids, including a higher level of saturated and lower levels of unsaturated fatty acids. An important exception was the presence of a monosaturated fatty acid whose GC retention time and mass spectrum were consistent with the uncommon cis-10-20:1 isomer. This pattern was associated with the presence of patient posterior hordeola. Thus, the association of triglyceride fatty acid composition with chronic blepharitis disease signs could be much more important than previously thought. Furthermore, this is the first example of the association of specific fatty acids with a specific chronic blepharitis disease sign.

Blepharitis↗
PubMed1995

Acanthamoeba keratitis.

The incidence of Acanthamoeba keratitis has decreased significantly, and it is no longer a reportable condition in the United States. Corneal abrasion and contact lenses play an important role in the development of Acanthamoeba keratitis. One of the most important features of the disease is severe pain, which is atypical for herpes simplex. The pathognomonic sign for Acanthamoeba is radial neuritis or inflammation around the corneal nerve caused by the parasites. The most important step in prevention of Acanthamoeba keratitis is effective education of patients about the care of contact lenses. A combination of Brolene and Neomycin is the best approach in treating Acanthamoeba keratitis. However, if treatment with these drugs fails, clotrimazole is recommended.

Acanthamoeba Keratitis↗
PubMed1995

Successful immunization against Acanthamoeba keratitis in a pig model.

The feasibility of inducing protective immunity to Acanthamoeba keratitis was tested in a pig model. Experiments were designed to determine if ocular infection with Acanthamoeba trophozoites would elicit protection against reinfection. Additional experiments examined whether injection of parasite antigens either intramuscularly, subconjunctivally, or by both routes would induce immunity. Therefore, four groups of animals were examined: (a) pigs that had resolved a primary corneal infection with Acanthamoeba; (b) pigs immunized intramuscularly; (c) pigs immunized subconjunctivally; and (d) pigs immunized intramuscularly and subconjunctivally. Animals were subsequently challenged with parasite-laden soft contact lenses and observed clinically for the appearance of Acanthamoeba keratitis. Acanthamoeba-specific serum antibody titers and blastogenic responses of peripheral blood lymphocytes were determined weekly. The results indicated that intramuscular injection of Acanthamoeba antigens failed to protect against ocular infection even though hosts developed high titers of IgG antibodies and displayed lymphocyte blastogenic responses to parasite antigens. Ocular infection alone failed to stimulate immunity in any of the animals. By contrast, 50% of the hosts immunized subconjunctivally were protected against corneal disease, and 100% of the animals immunized by a combination of intramuscular and subconjunctival administration of parasite antigens were completely protected against two separate ocular challenges with infectious parasites. Protection did not correlate with either IgG antibody titers or blastogenic potentials of peripheral blood lymphocytes. Interestingly, ocular infection alone failed to stimulate immunity to subsequent ocular challenge with infectious parasites. Thus, administration of parasite antigen via the subconjunctival route can protect against Acanthamoeba keratitis.

Acanthamoeba↗
PubMed1994

Efficacy of lodoxamide 0.1% ophthalmic solution in resolving corneal epitheliopathy associated with vernal keratoconjunctivitis.

A multicenter, randomized, double-masked, parallel-group study compared the long-term efficacy and safety of lodoxamide 0.1% ophthalmic solution and placebo in 118 patients with vernal keratoconjunctivitis. The test drugs were instilled four times daily for 90 days. Lodoxamide 0.1% ophthalmic solution was significantly (P < .05) more effective than placebo in lowering severity scores for epithelial disease and corneal staining, evidence of the superior efficacy of lodoxamide 0.1% ophthalmic solution in reversing the corneal complications commonly associated with moderate to severe vernal keratoconjunctivitis. Additionally, lodoxamide 0.1% ophthalmic solution ameliorated the other key signs of vernal keratoconjunctivitis, including upper tarsal papillae, limbal signs (papillae, hyperemia, and Trantas' dots), and conjunctival discharge. The between-group differences in the relief of symptoms (itching, tearing, and photophobia) were clinically significant but not always statistically significant. Treatment-related adverse events were reported with similar frequency in both treatment groups, and none were serious.

Adolescent↗
PubMed1994

Antibody-dependent neutrophil-mediated killing of Acanthamoeba castellanii.

Neutrophils from naive rats lysed low numbers of Acanthamoeba castellanii in the presence of normal rat serum and significantly higher numbers of the parasite in the presence of serum from immunized rats. With normal rat serum, neutrophils from rats immunized with crude parasite extract or from naive rats killed similar percentages of A. castellanii. However, neutrophils from immunized rats killed a significantly greater percentage of parasites in the presence of serum from immunized rats than was seen with any other combination of serum and neutrophils. The addition of supernatant from cultures of concanavalin A-stimulated rat spleen cells to incubations of the parasite in the presence of neutrophils from naive or immunized rats and immune serum resulted in the highest levels of amoebolysis seen in this study. This study has shown that neutrophils from naive rats or from rats immunized with A. castellanii antigen display a very limited amoebolytic capability which is significantly augmented in the presence of serum from immunized rats and further boosted by the addition of supernatant from Con A-stimulated rat spleen cell cultures.

Acanthamoeba↗
PubMed1994

Demonstration of feasibility of application of a portable keratometer to cadaveric donor corneas.

An automated portable keratometer was used to measure corneal curvatures of cadaveric donor corneas. Globe contours were maintained despite unrecordable intraocular pressures, and reproducible keratometric values were consistently obtainable. Evaluation of nondonor eyes, at varying intraocular pressures (IOPs) ranging from 0 to 66 mm Hg (Schiotz), yielded keratometric readings that were not significantly different at different IOPs. Early correlation of keratometric values in five grafted eyes showed a trend of +/- 0.5 D from measured cadaveric donor keratometry values when compared with that of the donor sutured into the recipient bed. The study suggests the feasibility of incorporating cadaveric donor keratometry readings in the prediction of final donor keratometric values in the recipient bed, thus allowing more accurate selection of intraocular lens powers for triple procedures and the avoidance of transplanting corneas with unusual or abnormal corneal curvatures.

Aged↗
PubMed1994

Apoptosis as a mechanism of cytolysis of tumor cells by a pathogenic free-living amoeba.

Previous studies have shown that trophozoites of the pathogenic free-living amoeba Acanthamoeba castellanii rapidly lysed a variety of tumor cells in vitro. Tumor cells undergoing parasite-mediated lysis displayed characteristic cell membrane blebbing reminiscent of apoptosis. The present investigation examined the role of apoptosis (programmed cell death) in Acanthamoeba-mediated tumor cell lysis. The results showed that more than 70% of tumor cell DNA was fragmented following exposure to Acanthamoeba cell extracts. By contrast, only 7% of untreated control cells underwent DNA fragmentation. DNA fragmentation increased significantly in a dose-dependent fashion following concentration of the parasite extract. Apoptosis was also confirmed by DNA ladder formation. Characteristic DNA ladders, consisting of multimers of approximately 180 to 200 bp, were produced by tumor cells exposed to Acanthamoeba cell extracts. The morphology of tumor cell lysis was examined by light and scanning electron microscopy. Tumor cells exposed to parasite extract displayed morphological features characteristic of apoptosis including cell shrinkage, cell membrane blebbing, formation of apoptotic bodies, and nuclear condensation. By contrast, similar effects were not found in tumor cells exposed to extract similarly prepared from normal mammalian cells (i.e., human keratocytes). The results suggest that at least one species of pathogenic free-living amoeba is able to lyse tumor cells by a process that culminates in apoptosis.

Acanthamoeba↗
PubMed1993

In vitro and in vivo tumoricidal properties of a pathogenic/free-living amoeba.

The chemotactic and tumoricidal properties of the pathogenic/free-living amoeba Acanthamoeba castellanii were examined in vivo and in vitro. A. castellanii trophozoites displayed strong positive chemotactic responses to human melanoma (OCM-1) and murine melanoma (D5.1G4) cells. Although the parasites typically invade and destroy the corneal epithelium and stroma, positive chemotactic responses were not detected against extracts of either of these corneal elements. In vitro studies revealed that viable parasites, as well as cell-free parasite lysates, produced swift and extensive cytolysis of a wide variety of tumor cells. The tumoricidal properties of A. castellanii were examined in vivo and revealed that injection of viable parasites or cell-free parasite lysates into progressively growing subcutaneous melanomas resulted in 83% and 53% reductions in the tumor masses compared with untreated controls. The feasibility of utilizing the tumoricidal properties of pathogenic/free-living amoebae and their cell-free products in the treatment of drug-resistant or radioresistant tumors warrants further investigation.

Acanthamoeba↗
PubMed1993

Clinical and diagnostic use of in vivo confocal microscopy in patients with corneal disease.

BACKGROUND: The purpose of this article is to introduce the practicing ophthalmologist to the optical principles and images produced by a tandem scanning confocal microscope (recently approved by the Food and Drug Administration for general clinical use). The tandem scanning confocal microscope allows real-time viewing of structures in the living cornea at the cellular level in four dimensions (x, y, z, and time). METHODS: Nine patients (2 males, 7 females), ranging in age from 7 to 52 years, were examined. Images were recorded on super VHS videotape, digitized and processed on a computer workstation, and photographed for presentation. RESULTS: Two-dimensional (x, y) 400 x 400-microns images (9-microns z-axis thickness) are presented for normal corneal structures and for the clinical conditions of herpetic keratitis, wound healing after myopic excimer ablation, Acanthamoeba infection, corneal dystrophies (granular, Reis-Buckler), contact lens abrasion, and the irido-corneal endothelial syndrome. CONCLUSION: Clinical confocal microscopy has the unique potential of providing noninvasive assessment of corneal injury and disease at the cellular level that is not available currently from other technologies.

Acanthamoeba Keratitis↗