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Biomedical subjects

T P O'Brien

Publications and source records attributed to T P O'Brien.

At least 19 recordsLinked to original sources
PubMed2005

Emerging guidelines for use of NSAID therapy to optimize cataract surgery patient care.

This analysis provides guidelines for the proper use of topical ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs), discusses their effect on inflammation, and their role in the prevention of cystoid macular edema (CME). A novel treatment strategy is presented for recommended topical ophthalmic NSAID dosing in patient populations based on risk factors for CME. The article reviews current topical ophthalmic NSAIDs, as well as a newest generation of pro-drug NSAIDs. In addition, combination therapy of NSAIDs and corticosteroids are discussed, along with a general review of therapeutic guidelines for dosing regimens, and benefits and risks of therapy. The goal of this analysis is to provide a suggested therapeutic regimen with topical NSAIDs to assist in achieving optimal clinical and functional outcomes.

Adrenal Cortex Hormones↗
PubMed2001

The role of apoptosis in the pathogenesis of Fuchs endothelial dystrophy of the cornea.

OBJECTIVE: To investigate the potential role of apoptosis in the pathogenesis of Fuchs endothelial dystrophy of the cornea. METHODS: Twenty-one corneal buttons from patients with Fuchs dystrophy and 15 control corneas were studied. Apoptosis was assessed by the in situ end-labeling of double-stranded DNA breaks, and by immunohistochemical characterization of cellular markers associated with apoptosis (Fas, FasL, Bcl-2, and Bax). Expression of Bcl-2 and Bax mRNA in the corneal stroma and endothelium was separately analyzed by a semiquantitative reverse transcriptase polymerase chain reaction. Furthermore, cultivated keratocytes generated from diseased corneal buttons and donor rims were exposed to camptothecin, an apoptotic inducer, for 6 and 24 hours. They were then examined for protein and messenger RNA (mRNA) expression of apoptotic regulatory molecules. RESULTS: DNA fragmentation was seen in the epithelium, stroma, and endothelium in 6 of 7 corneas with Fuchs dystrophy. A statistically significant difference was identified in the expression of Bax and its mRNA in the stroma, but not in the endothelium of Fuchs dystrophy corneas. Following exposure to camptothecin, keratocytes from patients with Fuchs dystrophy responded with an increased level of Bax and a low level of Bcl-2. This trend was distinctively different from the response of normal keratocytes. CONCLUSIONS: The evidence in this study points to a disease-related disturbance in the regulation of apoptosis in Fuchs dystrophy. Our findings suggest that excessive apoptosis may be an important mechanism in the pathogenesis of Fuchs dystrophy.

Aged↗
PubMed2001

The role of matrix metalloproteinases in ulcerative keratolysis associated with perioperative diclofenac use.

OBJECTIVE: To investigate the role of matrix metalloproteinases (MMPs) in the pathogenesis of ulcerative keratolysis associated with topical use of generic diclofenac preoperatively and postoperatively. To characterize the inflammatory response of the cornea in this case of ulcerative keratolysis. DESIGN: Case report with clinicopathologic correlation. MAIN OUTCOME MEASURES: Corneal culture for microbial growth. Clinical and histopathologic examinations including routine histolopathologic, immunofluorescent, and immunohistochemical studies. RESULTS: Microscopic examination of the corneal button disclosed fibrinous material with neutrophils and mononuclear inflammatory cells. The corneal epithelial basement membrane was irregularly thickened and patchy. Immunohistochemical staining detected weak staining of MMP-1 and a strong presence of MMP-8 in the epithelium. MMP-8 and 9 were also present in areas of leukocytic infiltration. MMP-2 appeared in a few stromal cells. Macrophages and leukocytes were the predominant infiltrating cells. CONCLUSIONS: A nonspecific inflammatory response occurred in this case of ulcerative keratolysis. Corneal epithelial cells are capable of secreting MMP-1 and 8 and may participate in the stromal degradation and repair process of the ulcerative keratolysis associated with topical nonsteroidol antiinflammatory use.

Aged↗
PubMed2001

Long-term survival of allogeneic donor cell-derived corneal epithelium in limbal deficient rabbits.

PURPOSE: To investigate the capability of cultivated allogeneic epithelial stem cells to restore a functional ocular surface in a limbal deficient cornea; to verify the long term survival of epithelial allograft; and to examine the host immune response to heterologous cell transplant in a rabbit model. METHODS: Limbal deficiency was established by performing limbectomy on rabbits (n = 100). Corneal epithelial stem cells were obtained from the limbus and replicated in vitro without a supporting layer. The cell (3 x 10(5)) suspension was then transplanted via topical application as eye drops. Animals were divided into allograft, autograft, and control groups. Females were used as recipients and males as donors for the allograft. Corneas were collected at 7, 14, 21, 40 days as well as 2, 3, 7 and 8 months after cell transplantation. Experimental corneas were evaluated by histology, immunofluorescence, immunohistochemistry and Y chromosome analysis. RESULTS: A well-differentiated corneal epithelium was recognized at 14 to 40 days after cell transfer overlying an infiltrated corneal stroma. Corneal re-epitheliazation was confirmed in 31 of 36 allograft corneas. No significant immune rejection was noted. Stromal abnormality caused by previous limbal deficiency was mostly resolved three months after the regeneration of corneal epithelium. CONCLUSIONS: Transplanted corneal epithelial stem cells were able to differentiate into normal corneal epithelium in vivo without the use of membrane scaffolding. This non-autologous donor cell-derived corneal epithelium survived up to 8 months without immunosuppression and was able to reverse the stromal scarring. Thus, cultivated epithelial stem cells have great potential as an alternative to multiple-surgical procedures in the treatment of limbal deficiency states.

Animals↗
PubMed2001

Molecular and functional mapping of the piebald deletion complex on mouse chromosome 14.

The piebald deletion complex is a set of overlapping chromosomal deficiencies surrounding the endothelin receptor B locus collected during the Oak Ridge specific-locus-test mutagenesis screen. These chromosomal deletions represent an important resource for genetic studies to dissect the functional content of a genomic region, and several developmental defects have been associated with mice homozygous for distinct piebald deletion alleles. We have used molecular markers to order the breakpoints for 20 deletion alleles that span a 15.7-18-cM region of distal mouse chromosome 14. Large deletions covering as much as 11 cM have been identified that will be useful for regionally directed mutagenesis screens to reveal recessive mutations that disrupt development. Deletions identified as having breakpoints positioned within previously described critical regions have been used in complementation studies to further define the functional intervals associated with the developmental defects. This has focused our efforts to isolate genes required for newborn respiration and survival, skeletal patterning and morphogenesis, and central nervous system development.

Alleles↗
PubMed2001

In vitro susceptibilities of bacterial ocular isolates to fluoroquinolones.

PURPOSE: To evaluate and compare the in vitro antimicrobial activity of levofloxacin versus ciprofloxacin and ofloxacin against ocular isolates from patients with bacterial conjunctivitis. METHODS: The in vitro antimicrobial susceptibilities of ocular isolates to levofloxacin, ofloxacin, and ciprofloxacin were determined using both the agar disk diffusion and broth dilution methods. RESULTS: Disk diffusion susceptibility testing disclosed that 99% (100 of 101 isolates) of gram-negative isolates and 98% (127 of 129 isolates) of gram-positive isolates were susceptible to levofloxacin; 96% (97 of 101 isolates) of gram-negative isolates and 78% (100 of 129 isolates) of gram-positive isolates were susceptible to ofloxacin; and 94% (95 of 101 isolates) of gram-negative isolates and 61% (79 of 129 isolates) of gram-positive isolates were susceptible to ciprofloxacin. Broth dilution testing disclosed that 99% (72 of 73 isolates) of gram-negative isolates and 98% (111 of 113 isolates) of gram-positive isolates were susceptible to levofloxacin; 96% (70 of 73 isolates) of gram-negative isolates and 92% (104 of 113 isolates) of gram-positive isolates were susceptible to ofloxacin; and 95% (69 of 73 isolates) of gram-negative isolates and 82% (93 of 113 isolates) of gram-positive isolates were susceptible to ciprofloxacin. CONCLUSIONS: In this study, levofloxacin demonstrated superior in vitro activity against human bacterial conjunctival isolates compared with either ofloxacin or ciprofloxacin (levofloxacin > ofloxacin > ciprofloxacin).

Anti-Infective Agents↗
PubMed2000

Loss of late primitive streak mesoderm and interruption of left-right morphogenesis in the Ednrb(s-1Acrg) mutant mouse.

This study characterizes defects associated with abnormal mesoderm development in mouse embryos homozygous for the induced Ednrb(s-1Acrg) allele of the piebald deletion complex. The Ednrb(s-1Acrg) deletion results in recessive embryonic lethality and mutant embryos exhibit a truncated posterior body axis. The primitive streak and node become disfigured, consistent with evidence that cell migration is impaired in newly formed mesoderm. Additional defects related to mesoderm development include notochord degeneration, somite malformations, and abnormal vascular development. Arrested heart looping morphogenesis and a randomized direction of embryonic turning indicate that left-right development is also perturbed. The expression of nodal and leftb, Tgf-beta-related genes involved in a left-determinant signaling pathway, is variably lost in the left lateral plate mesoderm. Mutational analysis has demonstrated that Fgf8 and Brachyury (T) are required for normal mesoderm and left-right development and the asymmetric expression of nodal and leftb. Fgf8 expression in nascent mesoderm exiting the primitive streak is dramatically reduced in mutant embryos, and diminished T expression accompanies the progressive loss of paraxial, lateral, and primitive streak mesoderm. In contrast, axial mesoderm persists and T and nodal appear to be appropriately expressed in their specific domains in the node and notochord. We propose that this mutation disrupts a morphogenetic pathway, likely involving FGF signaling, important for the development of streak-derived posterior mesoderm and lateral morphogenesis.

Alleles↗
PubMed2000

Acute unilateral corneal immunoprotein deposition in IgM monoclonal gammopathy.

A healthy 43-year-old officer of a merchant ship at sea developed pain, redness, and photophobia in his right eye. During the next 2 weeks, he noted the presence of a band of opacity spreading from his temporal limbus toward his central cornea. His episcleral vessels were engorged in a distribution contiguous with the peripheral, sectorial, fleck-like corneal opacities. The opacity had progressed during topical and systemic antibiotic therapy, but halted with use of topical corticosteroids. Systemic evaluation showed mild IgM monoclonal gammopathy. Transmission electron microscopy of a corneal biopsy specimen revealed electron-dense fibrils identified as immunoprotein. To our knowledge, this is the first report of a case of acute unilateral deposition of corneal immunoprotein in a patient with monoclonal gammopathy. Clinicians should begin with a broad differential diagnosis when evaluating patients with corneal opacity.

Acute Disease↗
PubMed2000

Mechanisms of retention of pyrrolidinyl norephedrine on immobilized alpha(1)-acid glycoprotein.

The HPLC separation of the R,S and S,R enantiomers of pyrrolidinyl norephedrine on immobilized alpha-1 glycoprotein (AGP) was investigated. Conditions for the separation were varied using a premixed mobile phase containing an ammonium phosphate buffer and an organic modifier. The influence of mobile phase pH, ionic strength, organic modifier composition, modifier type, and temperature on the chiral selectivity and retention were investigated. The presented data demonstrate that independent phenomena govern the enantioselectivity and retention. Retention is a function of both ion exchange equilibria and hydrophobic adsorption. Thermodynamic data derived from van't Hoff plots illustrates that while enantioselectivity is also enthalpically driven, the magnitude of the enthalpy term is governed by pH. Enantioselectivity has little dependence on ionic strength. Hydrophobic interactions appear to foster hydrogen bonding interactions; the two appear to be mutually responsible for chiral selectivity. The chiral selectivity decreases as the pH is decreased and increases with mobile phase buffer strength.

Chromatography, High Pressure Liquid↗
PubMed2000

The role of apoptosis in the early corneal wound healing after excimer laser keratectomy in the rat.

BACKGROUND: The potential role of apoptosis in corneal wound healing after excimer laser keratectomy was investigated in a rat model. METHODS: Lewis rats underwent laser keratectomy using a 193-nm excimer laser. The central corneas were ablated in three depths: group A, epithelium; group B, superficial stroma; group C, deep stroma. Eyes were collected at 1, 12, 24, and 36 h and 1 week. Cellular markers associated with apoptosis--Fas, Fas ligand (FasL), Bcl-2, and Bax were examined by immunohistochemistry. Keratocyte depletion and endothelial changes were evaluated histologically. In situ end labeling of double-stranded DNA breaks was used to demonstrate apoptosis in corneal sections. RESULTS: Keratocyte depletion was observed in 6 (50%) of 12 rats (total from groups A, B, and C) at 12 h, 11 (73%) of 15 at 24 h, 3 (20%) of 15 at 36 h, and 2 (15%) of 13 at 1 week after laser surgery. Corneal endothelial edema was observed in the ablation zone. Expression of Fas, FasL, Bcl-2, and Bax in corneal cells showed dynamics similar to that of keratocyte depletion and endothelial changes. There was less expression of apoptotic molecules in newly generated epithelial cells and more in endothelial cells of the stromal ablation groups. CONCLUSIONS: Excimer laser keratectomy triggered apoptosis of corneal keratocytes and endothelial cells. More endothelial edema was observed in the stromal ablation than in the epithelial ablation group. The expression of apoptotic molecules coincided with the period of keratocyte depletion and regeneration and of endothelial recovery, suggesting that apoptosis is a dynamic part of corneal wound healing and remodeling after excimer laser keratectomy.

Animals↗
PubMed2000

Herpes simplex virus DNA identification from aqueous fluid in Fuchs heterochromic iridocyclitis.

PURPOSE: To report the presence of herpes simplex virus DNA in the aqueous humor of an eye with Fuchs heterochromic iridocyclitis. METHODS: In an eye with a clinical diagnosis of Fuchs heterochromic iridocyclitis, samples of aqueous humor and anterior capsule of the lens were obtained during cataract surgery. Polymerase chain reaction was performed on the samples to detect the presence of viral DNA including herpes simplex virus, varicella-zoster virus, and cytomegalovirus. Serologic analysis was also performed for antiviral immunoglobulins. RESULTS: Herpes simplex virus DNA was identified in the aqueous humor but not in the anterior capsule. Serum immunoglobulin G was positive for herpes simplex virus, varicella-zoster virus, and cytomegalovirus. CONCLUSIONS: The presence of herpes simplex virus DNA in the aqueous humor of an eye with Fuchs heterochromic iridocyclitis suggests that herpes simplex virus infection may play a role in the pathogenesis of Fuchs heterochromic iridocyclitis.

Adult↗
PubMed2000

Late traumatic dislocation of laser in situ keratomileusis corneal flaps.

PURPOSE: To report the management and outcome of late-onset traumatic dislocation of laser in situ keratomileusis (LASIK) flaps. DESIGN: Retrospective, observational case series. PARTICIPANTS: Four patients with late-onset LASIK flap dislocation occurring after mechanical trauma at various intervals (10 days-2 months) after the procedure. INTERVENTION: In all cases of postoperative traumatic LASIK flap dislocation, the flap was refloated with scraping and irrigation of the underlying stromal bed within 12 hours of the injury. A bandage contact lens was placed, and a regimen including topical antibiotics and corticosteroids was instituted in all cases. MAIN OUTCOME MEASURES: Best spectacle-corrected visual acuity and complications associated with the surgery were monitored. RESULTS: Postoperative follow-up ranged from 4 to 21 months. Nonprogressive epithelial ingrowth was noted in one patient and diffuse lamellar keratitis developed in another patient. All patients recovered pretrauma spectacle-corrected visual acuity. CONCLUSIONS: Corneal LASIK flaps are prone to mechanical dislocation as late as 2 months after the procedure. Appropriate management results in recovery of optimal visual outcomes.

Adult↗
PubMed2000

Management of flap striae.

There have been no comprehensive investigations of striae after LASIK. The ophthalmic literature has few reports, and no one consistent therapy has been recommended. Striae are relatively uncommon; nevertheless, refractive surgeons need a systematic approach in prevention and therapy for striae. Careful flap handling and positioning can prevent many striae. Early recognition is very important and makes treatment significantly more likely to eliminate or reduce the striae. If the striae are identified within 24 hours, lifting and refloating will likely result in resolution of the striae. If the striae are more imbedded and have been present longer, additional techniques, such as those discussed, are helpful. New techniques will likely be developed because of an increase in lamellar procedures and an increase in the occurrence of striae.

Contact Lenses↗
PubMed2000

Comparison of cerebrovascular effects of intravenous cocaine injection in fetal, newborn, and adult sheep.

Cocaine may cause stroke, intracranial hemorrhage, seizures, and neurobehavioral abnormalities in fetuses, newborns, and adults, and there could be developmental and/or species differences in mechanisms for these cocaine-induced cerebrovascular effects. To evaluate developmental differences in responses to cocaine, we compared the cerebrovascular and metabolic responses to a 2 mg/kg iv cocaine dose in unanesthetized fetal (n = 8, previously reported, direct fetal injection), newborn (n = 6), and adult (n = 12) sheep. We measured cerebral blood flow, mean arterial blood pressure, and arterial and venous O(2) content, and we calculated cerebral O(2) consumption and cerebral vascular resistance at baseline and at 30 s and at 5, 15, and 60 min after cocaine injection. Cerebral blood flow increased 5 min after injection in the fetus and newborn, but not until 15 min in the adult. In the fetus, cocaine caused a transient cerebral vasoconstriction at 30 s; in all three groups, cocaine caused cerebral vasodilation, which was delayed in the adult. Cerebral metabolic O(2) consumption increased 5 min after injection in the fetus and newborn, but not until 15 min after injection in the adult. Arterial O(2) content decreased 5 min after injection in the fetus and 15 min after injection in the adult. We speculate that clinical differences in response to cocaine injection may be explained, in part, by these developmental differences in the cerebrovascular and metabolic responses to cocaine.

Animals↗
PubMed2000

The subspecialty training, practice type, and geographical distribution of recently trained ophthalmologists: a study of male and female physicians.

OBJECTIVE: To characterize the distribution of male and female ophthalmologists with regard to practice type, subspecialty training, rural-urban distribution, and regional distribution. METHODS: Ophthalmology Matching Program files containing the records of residents who began their second year at accredited programs between 1986 and 1990 (inclusive), were compared to membership files of the American Academy of Ophthalmology. Practice locations for each individual were classified according to region, stage, and Rural-Urban Continuum County Code, as defined by the US Department of Agriculture. RESULTS: This cohort comprised 2,494 individuals, 77.1% (1922) of whom were male and 22.9% (572) of whom were female. Group practice was most common (55.9% for women and 61.3% for men). More women were in salaried positions associated with health maintenance organizations (p = 0.006) and academic settings (p < 0.001) than were men. Notable differences in subspecialty choice were restricted to pediatric ophthalmology, chosen three times more frequently by women, and vitreoretinal diseases/surgery, chosen twice as often by men. Only 5.6% of women selected nonmetropolitan practice locales compared to approximately twice that percentage of men. The Middle Atlantic and New England regions attracted more women, while the South Atlantic attracted more men.

Cohort Studies↗