Biomedical subjects

Hilary W Thompson

Publications and source records attributed to Hilary W Thompson.

16 recordsLinked to original sources

PubMed2006

Apolipoprotein E modulates establishment of HSV-1 latency and survival in a mouse ocular model.

PURPOSE: To evaluate and compare the neuroinvasiveness and neurovirulence after ocular HSV-1 infection in ApoE knockout (ApoE-/-) and control C57BL/6 (ApoE+/+) mice. METHODS: Age-matched (14 weeks of age) C57BL/6J (ApoE+/+) female mice and female ApoE knockout (ApoE-/-) mice were inoculated by corneal scarification with HSV-1 strain 17Syn+. Analysis of HSV-1 replication in the mouse cornea was assessed through infectious virus assays of ocular (tear film) swabs at 1 to 5 days postinoculation (PI), slit-lamp examination (SLE) of corneas at PI days 1 to 7, and survival of infected mice. The contribution of apoE to the efficient establishment of latency was measured by real-time PCR quantitation of the latent viral genome in the trigeminal ganglia (TG) of infected mice. RESULTS: These studies showed that HSV-1 strain 17Syn+ replicates efficiently in the eyes, regardless of the host ApoE genotype. Neither the scoring of corneal pathology via SLE nor the infectious virus assay of the tear film resulted in any statistical differences between ApoE knockout (-/-) mice or the C57BL/6 (ApoE+/+) mice. In mice latently infected with HSV-1, our real-time PCR data showed significantly lower viral copy numbers of HSV-1 DNA in ApoE knockout (ApoE-/-) mice compared with C57BL/6 (ApoE+/+) mice. C57BL/6 (ApoE+/+) mice are more susceptible to the neurovirulence of HSV-1 strain 17Syn+ than female ApoE knockout (-/-) mice, as demonstrated by the fact that 50% (7/14) of the female C57BL/6 (ApoE+/+) mice inoculated with 17Syn+ died, as opposed to none (0/14) of the age- and sex-matched ApoE knockout mice. CONCLUSIONS: These data indicate that age (14 weeks) and sex-matched (female) wild mice with an ApoE null background (ApoE-/-) are more resistant and less efficient in the establishment of latency compared with ApoE+/+ mice in the C57BL/6 background.

Animals↗

PubMed2005

Long-term study of accommodative esotropia.

PURPOSE: This study aimed, using a large sample size, to determine the long-term results of standard treatment of accommodative esotropia and identify predictors of outcome while minimizing bias in data collection and analysis. METHODS: Data from all the files of a large, long-established pediatric ophthalmology practice were collected and analyzed using a masked protocol. The study included every esotropic patient who had been prescribed glasses. Criteria for patient inclusion were designed to conform to earlier studies by the authors. RESULTS: The database totaled 1307 patients, of who 354 met inclusion criteria. A greater difference between near and distance esodeviation (AC/A relationship) correlated with a higher rate of deterioration of accommodative esotropia control (P < 0.0001). Deterioration also positively correlated with earlier age of onset (P < 0.0001), inferior oblique overaction (P = 0.0005), and amblyopia (P < 0.005). CONCLUSIONS: This study demonstrates that a high AC/A relationship increases the likelihood of deterioration of accommodative esotropia, supporting the earlier studies, as well as the accuracy of this database. It also represents a new model for the utilization of clinical trials' bias-reduction principals in the analysis of retrospective data.

Accommodation, Ocular↗

PubMed2005

HSV-1 DNA in tears and saliva of normal adults.

PURPOSE: To assess the frequency of shedding of herpes simplex virus type 1 (HSV-1) DNA in tears and saliva of asymptomatic individuals. METHODS: Fifty subjects without signs of ocular herpetic disease participated. Serum samples from all subjects were tested for HSV IgG antibodies by enzyme-linked immunosorbent assay (ELISA) and for HSV-1 by neutralization assay. HSV-1 DNA copy number and frequency of shedding were determined by real-time polymerase chain reaction (PCR) analysis of tear and saliva samples collected twice daily for 30 consecutive days. RESULTS: Thirty-seven (74%) of the 50 subjects were positive for HSV IgG by ELISA. The percentages of positive eye and mouth swabs were approximately equivalent: 33.5% (941/2806) and 37.5% (1020/2723), respectively. However, the percentage of samples with high HSV-1 genome copy numbers was greater in saliva than in tears, which may have been a result of the sample volume collected. Shedding frequency in tears was nearly the same in men (347/1003; 34.6%) and women (594/1705; 34.8%); in saliva, men had a higher frequency of shedding (457/1009; 45.3% vs. 563/1703; 33.1%, men versus women). Overall, 49 (98%) of 50 subjects shed HSV-1 DNA at least once during the course of the 30-day study. CONCLUSIONS: The percentage of asymptomatic subjects who intermittently shed HSV-1 DNA in tears or saliva was higher than the percentage of subjects with positive ELISA or neutralization antibodies to HSV. Because most HSV transmission occurs during asymptomatic shedding, further knowledge of the prevalence of HSV-1 DNA in tears and saliva is warranted to control its spread. Shedding is simple to study, and its suppression may be an efficient way to evaluate new antivirals in humans.

Adult↗

PubMed2004

Bupropion (Zyban, Wellbutrin) inhibits nicotine-induced viral reactivation in herpes simplex virus type 1 latent rabbits.

We reported that nicotine applied via a transdermal patch (21 mg/day) induced viral reactivation and ocular shedding in herpes simplex virus type 1 (HSV-1) latent rabbits. One possible mechanism of action involves the release of catecholamines and other similar agents, triggering HSV reactivation. Bupropion (Zyban, Wellbutrin), a non-nicotine aid to smoking cessation, inhibits neuronal uptake of norepinephrine, serotonin, and dopamine. To determine whether bupropion inhibits HSV reactivation, rabbits latent with HSV-1 were grouped (at least 10 rabbits/group) and treated as follows: nicotine patch (transdermal delivery) and bupropion [Zyban sustained-release tablets (150 mg) twice a day (oral)], nicotine patch only, Zyban tablets only [twice a day (oral)], nicotine patch with oral placebo [twice a day (oral)], or no drug treatment. Eyes were swabbed for 22 consecutive days. The appearance of HSV-1 in the tear film was significantly less frequent in the bupropion-treated rabbits, in terms of positive rabbits/total rabbits, positive eyes/total eyes, and positive swabs/total swabs. Nicotine-treated rabbits had 78/440 (17.7%) positive/total swabs, and nicotine/placebo-treated rabbits had 149/792 (18.8%) positive/total swabs, whereas bupropion-treated rabbits had 23/440 (5.2%), and nicotine/bupropion-treated rabbits had 47/792 (5.9%) positive/total swabs. Thus, bupropion significantly reduces nicotine-induced HSV reactivation in latent rabbits.

Animals↗

PubMed2004

Comparison of retinal outcomes after scleral buckle or lens-sparing vitrectomy for stage 4 retinopathy of prematurity.

PURPOSE: To compare anatomic outcomes after lens-sparing vitrectomy (LSV) or scleral buckle (SB) for stage 4 retinopathy of prematurity (ROP). METHODS: Nonrandomized, retrospective study of infants consecutively treated for stage 4 ROP by LSV or SB. Outcomes were retinal attachment at 1 month of initial surgery and at the end of follow-up (6 months) and number of procedures to achieve retinal attachment. Exact chi2 methods determined significance, and student's t-test compared mean postmenstrual age and birthweight between the groups. RESULTS: After one procedure, LSV (72%) was associated with retinal attachment more often than was SB (31%). At the end of follow-up, after one or more procedures, there was no difference in retinal reattachment rate between LSV or SB as the first procedure. There were no differences between the surgical groups by mean postmenstrual age and birthweight or severity of ROP determined by zone, clock hours of ridge elevation, or quadrants of plus disease. CONCLUSION: This study supports the hypothesis that vitrectomy by LSV stops progressive stage 4 ROP. As an initial procedure, LSV was associated with retinal attachment more often than SB. Future prospective studies can determine the effects of LSV and SB on visual development in progressive stage 4 ROP.

Birth Weight↗

PubMed2003

Long-term vision results measured with Teller Acuity Cards and a new Light Perception/Projection Scale after management of late stages of retinopathy of prematurity.

OBJECTIVES: To report visual acuity (VA) measured by Teller Acuity Cards (TACs) and a new Light Perception/Projection (LPP) Scale in infants with regressed or treated stage 3, 4, or 5 retinopathy of prematurity (ROP), and to compare VA in eyes that underwent successful vitreoretinal surgery for stage 5 ROP with eyes with persistent retinal detachment. METHODS: Nineteen infants (35 eyes) underwent VA testing using TACs and the LPP scale. The correlation between the methods was determined. Comparisons in VA scores were made in eyes by stage of ROP at the first examination and retinal status at the end of follow-up and between eyes with successful surgical reattachment and persistent retinal detachment. RESULTS: Scores obtained with the LPP scale and TACs were highly correlated (Spearman rank-order correlation coefficient, 0.92; P<.001). Visual acuity was better in eyes with retinal attachment at the end of follow-up than in eyes with retinal detachment whether the ROP stage at first examination was 4A (n = 6), 4B (n = 16), or 5 (n = 6). In eyes that progressed to stage 5 ROP and had successful surgical retinal reattachment (n = 16), both methods of measurement yielded better visual function than in eyes with persistent retinal detachment. The LPP scale provided scores for eyes without quantifiable grating acuity determined with TAC. CONCLUSIONS: The LPP scale scores were correlated with TAC scores in infants with stages 3, 4, and 5 ROP. Surgical retinal reattachment in stage 5 ROP resulted in better visual function. The LPP scale may be useful in measuring low vision in infants without quantifiable grating acuity and with later stages of ROP.

Female↗

PubMed2003

Analyzing data in which the outcome is time to an event part II: The presence of multiple covariates.

In this article, the second of a series on the analysis of time to event data, we address the case in which multiple predictors (covariates) that may influence the time to an event are taken into account. The hazard function is introduced, and is given in a form useful for assessing the impact of multiple covariates on time to an event. Methods for the assessment of model fitting are also discussed and an example with cancer survival as outcome with the presence or absence of multiple genes as covariates is presented.

Humans↗

PubMed2003

Deformation of the lamina cribrosa and anterior scleral canal wall in early experimental glaucoma.

PURPOSE: To test the hypothesis that pathophysiologic deformation of the lamina cribrosa and anterior scleral canal wall underlies the onset of confocal scanning laser tomography (CSLT)-detected optic nerve head (ONH) surface change in early experimental glaucoma. METHODS: Both eyes of four normal (two normal eyes) monkeys and four with early glaucoma (one eye with laser-induced IOP elevation, observed until the onset of CSLT-detected ONH surface change) were enucleated immediately after death and immersion fixed at IOP 0 mm Hg. In an additional four normal monkeys and five with early glaucoma, both eyes were cannulated, and IOP set to 10 mm Hg in one normal eye and either 30 or 45 mm Hg in the other (normal or early-glaucoma) eye. After 15 to 80 minutes of acute IOP elevation, these nine monkeys were perfusion-fixed. Within images of serial sagittal sections of the ONH tissues in all 17 monkeys, anterior lamina cribrosa position, laminar thickness, and scleral canal diameter were measured. For each parameter, differences between the two eyes of each monkey and between treatment groups were assessed by ANOVA. RESULTS: Within the eyes of the eight monkeys with IOP 0 mm Hg, the lamina cribrosa was posteriorly displaced and thicker and the scleral canal was enlarged at Bruch's membrane and at the anterior laminar insertion in the early-glaucoma eyes compared with the contralateral normal eyes (plastic deformation). Within the high-IOP normal eyes, the lamina cribrosa was posteriorly displaced compared with that in the low-IOP normal eyes, but there were no significant differences in laminar thickness or scleral canal diameter (normal compliance). Within the high-IOP early-glaucoma eyes, the lamina cribrosa was posteriorly displaced and thicker and the scleral canal enlarged, compared with both low-IOP normal eyes and high-IOP normal eyes (hypercompliant deformation). Differences in laminar position between the high-IOP early-glaucoma eyes and the contralateral low-IOP normal eyes (hypercompliant plus plastic deformation) were more than eight times greater than the differences between the high-IOP normal eyes and the contralateral low-IOP normal eyes (normal compliance). CONCLUSIONS: Both plastic (permanent) and hypercompliant deformation of the lamina cribrosa and anterior scleral canal wall are present in young adult monkey eyes with early experimental glaucoma. These findings suggest that damage to the ONH connective tissues occurs early in the monkey model of experimental glaucoma.

Animals↗

PubMed2003

Coordinate activation of HIF-1 and NF-kappaB DNA binding and COX-2 and VEGF expression in retinal cells by hypoxia.

PURPOSE: Proinflammatory signaling mechanisms are implicated in the induction of retinal neovascularization (NV) during ischemic retinopathies. This study examined transcription factor (TF) AP-1, HIF-1, and NF-kappaB DNA-binding in relation to cyclooxygenase (COX)-2 and VEGF RNA and protein levels in hypoxia-triggered monkey choroidal retinal (RF/6A) endothelial cells. Effects of the carboxamide CGP43182 were tested on COX-2 and VEGF activation and prostaglandin (PG)E(2) release. METHODS: RF/6A cells were subjected to hypoxia for 1 and 3 hours, at which times RNA and proteins were isolated. Potential AP-1, hypoxia-inducible factor (HIF)-1 and NF-kappaB DNA-binding sites were identified using DNA sequence search algorithms and were analyzed using gel-shift assay. COX-2 and VEGF RNA, protein, and PGE(2) levels were quantified by RT-PCR, Western analysis, and enzyme immunoassay, respectively. Tubular morphogenesis was analyzed with phase-contrast imaging microscopy. RESULTS: Nuclear AP-1, HIF-1 and NF-kappaB promoter DNA binding increased 1.5-, 4-, and 3-fold, respectively, after 1 hour of hypoxia. COX-2 RNA was elevated five- and fourfold after 1 and 3 hours of hypoxia, respectively. VEGF RNA and protein abundance lagged behind COX-2 induction but were each increased two- to threefold 3 hours after hypoxia. CGP43182 was found to inhibit NF-kappaB DNA binding, COX-2 and VEGF gene expression, PGE(2) release, and hypoxia-induced tubular morphogenesis. CONCLUSIONS: Maximum HIF-1 and NF-kappaB DNA binding immediately before COX-2 expression suggests that these TFs are important regulators of COX-2 induction in hypoxic RF/6A cells. IL-1beta emulated AP-1, HIF-1, and NF-kappaB DNA binding during hypoxia and may be a novel cytokine trigger for NV. CGP43182 appears to be an effective inhibitor of NV. VEGF expression appears to be regulated through dual interdependent mechanisms involving HIF-1 directly and indirectly through NF-kappaB-mediated COX-2 expression and PGE(2) production.

Animals↗

PubMed2003

Long-term study of accommodative esotropia.

PURPOSE: Previous studies of accommodative esotropia have been hampered by bias-prone methods of data collection and analysis and by small sample size. The studies have conflicting conclusions, causing uncertain results. This study aims to determine long-term results of standard treatment of accommodative esotropia and identify predictors of outcome, while minimizing bias in data collection and analysis, using the largest possible sample size. METHODS: A research assistant collected data from all files of a large, long-established pediatric ophthalmology practice (M.M.P.). The assistant was given standardized collection forms that allowed inclusion of all patient data points over all visits. The assistant was masked as to study goals. She was instructed to include any patient with esotropia who had been prescribed glasses during treatment. Descriptive terms were converted to code numbers. A second, similarly masked research assistant entered data into a computerized database. Criteria for patient inclusion were designed to conform to earlier studies by I.H.L. and M.M.P. and were implemented by computer. RESULTS: The database totaled 1,307 patients (747,717 data points). Of these, 354 qualified for this analysis. A greater difference between near and distance esodeviation (AC/A relationship) correlated with a higher rate of deterioration of accommodative esotropia control (P<.0001). Deterioration also positively correlated with earlier age at onset, inferior oblique overaction, and amblyopia. CONCLUSIONS: This study agrees with our previous findings that a high AC/A relationship increases the likelihood of deterioration of accommodative esotropia, thus confirming the integrity of the database. This unique, unbiased dataset will be used for future analyses of esotropia.

Accommodation, Ocular↗

PubMed2002

Clinician change detection viewing longitudinal stereophotographs compared to confocal scanning laser tomography in the LSU Experimental Glaucoma (LEG) Study.

PURPOSE: To compare optic nerve head (ONH) surface change detection by confocal scanning laser tomography (CSLT) within the LSU Experimental Glaucoma (LEG) study to expert clinicians viewing the LEG stereophotographs. DESIGN: Experimental study. PARTICIPANTS: Four fellowship-trained glaucoma specialists. METHODS: In the LEG study, six 15 CSLT images (TopSS, Laser Diagnostics Technologies, San Diego, CA) and four 2x optic disc stereophotographs were obtained from both eyes of 12 monkeys on 3 separate days and then every 2 weeks after laser to one eye (study eye) to elevate intraocular pressure. ONH surface change detection within the CSLT images is described in our companion report. In this report, the preliminary study compared change detection by the CSLT multivariate strategy with that of a single clinician viewing stereophotograph pairs on three separate occasions as the "gold standard." The main study compared change detection by three additional clinicians viewing a subset of LEG stereophotograph pairs on three separate occasions with that of the CSLT multivariate strategy as the "gold standard." Clinician change detection was assessed for partial (two of three occasions) or complete (three of three occasions) agreement. Three comparison groups within the main study are emphasized: 44 group A comparisons assessed false-positive change detection (specificity); 38 group B comparisons assessed change detection within 38 instances (11 onset and 27 progression events) of CSLT-detected study eye change; and 30 group C comparisons assessed change detection within 30 instances in which the CSLT failed to detect change in study eyes. MAIN OUTCOME MEASURES: Clinician change detection within each comparison with either partial or complete agreement. RESULTS: Within the main study, intrareading (-.29 to 0.67) and interreading (0.24--0.56) session agreement for each clinician was slight to moderate by kappa test. Good specificity (less than 10% false-positive change detection) was achieved within the 44 group A comparisons by two of the three clinicians, but only when the more stringent criterion (change detection on three of three occasions) was applied. Of the 38 group B comparisons (in which the CSLT detected change), the two clinicians who achieved good specificity in group A failed to detect change in 25 and 16 instances, respectively, using the more stringent (three of three) criterion. Similarly, of the 30 group C comparisons (in which the CSLT failed to detect change), these two clinicians detected change in three and seven instances, respectively, but in only one comparison did they both detect change. CONCLUSIONS: This study provides the first direct evidence that an existing CSLT may reasonably meet or exceed the ONH surface change detection performance of fellowship-trained glaucoma specialists in at least those eyes with good CSLT reproducibility.

Animals↗

PubMed2002

Change detection in regional and volumetric disc parameters using longitudinal confocal scanning laser tomography.

PURPOSE: To develop a clinically specific strategy for optic nerve head (ONH) surface change detection within longitudinally acquired confocal scanning laser tomographic (CSLT) images. DESIGN: Experimental study. PARTICIPANTS AND/OR CONTROLS: Twelve monkeys, each with one glaucomatous and one contralateral normal eye. MAIN OUTCOME MEASURES: Detection of ONH surface change within the CSLT images of each monkey's glaucomatous eye. METHODS: Six 10 and six 15 CSLT images and four stereo optic disc photographs were obtained from both eyes of 12 monkeys on 3 separate days (imaging sessions) and then every 2 weeks after laser to one eye (study eye) to elevate intraocular pressure. For each set of 10 and 15 images per eye (and for each of the 7-25 imaging sessions per monkey), 37 CSLT parameters were calculated. Univariate change required an individual parameter to change in excess of its analysis of variance-determined minimum detectable change (MDC) value. Multivariate change required groups of three parameters, considered together, to demonstrate significant change as determined by a multivariate analysis of variance. The rate of false-positive change detection for each individual parameter and for a group of three-parameter combinations was determined using both a one-in-a-row strategy (change at a single session) and a two-in-a-row strategy (change at two successive sessions) within the postlaser images of the 12 unchanging contralateral normal eyes. Change detection within the study eye images was then assessed for only those individual parameters and three-parameter combinations that were clinically specific (i.e., showed less than 10% false-positive change detection in the normal eyes). RESULTS: A total of 36 prelaser (three per monkey) imaging sessions and 158 postlaser (4-22/monkey) imaging sessions was performed. Clinically specific change detection (low rate of false positives) was achieved only with the two-in-a-row strategy. Overall, multivariate ONH surface change detection performed best; the best-performing three-parameter combination detected only 8 change events (4 onset and 4 progression) in 139 imaging sessions within the postlaser imaging sessions of the contralateral normal eyes and a total of 47 change events (11 onset and 36 progression) within the postlaser imaging sessions of the 12 study eyes. Counterintuitive (anterior) change occurred in most parameters within the late postlaser imaging sessions of the study eyes followed to end-stage damage. CONCLUSIONS: Clinically specific detection of the onset and progression of glaucomatous ONH surface change is possible within longitudinally acquired CSLT images.

Animals↗

PubMed2002

Corneal pathogenesis of Staphylococcus aureus strain Newman.

PURPOSE: To determine the pathogenic role of gamma- and alpha-toxin in a rabbit model of Staphylococcus aureus keratitis. METHODS: S. aureus strains Newman (expressing gamma-toxin), Newman Delta(hlg) (deficient in gamma-toxin), Newman Delta(hlg)/pCU1 hlg(+) (chromosomal gamma-toxin-deficient mutant rescued by a plasmid encoding gamma-toxin), and Newman Delta(hla) (alpha-toxin-deficient) were intrastromally injected into rabbit corneas. Eyes were scored by slit lamp examination (SLE), and bacterial colony-forming units (CFU) per cornea were determined at 15, 20, and 25 hours after infection. Histologic examination of corneas was performed. Rabbits were immunized against alpha-toxin and subsequently challenged with S. aureus strain Newman. Western blot analyses of culture supernatants were performed to detect alpha-toxin production. RESULTS: All strains grew equivalently, producing approximately 7 log CFU per cornea at 25 hours after infection. SLE scores at 20 and 25 hours after infection revealed that strains Newman Delta(hlg) and Newman Delta(hla), although virulent, caused significantly less ocular damage and inflammation than their parent or the gamma-toxin genetically rescued strain (P <or= 0.0006). Histologic and SLEs revealed that all strains except Newman Delta(hla) produced corneal erosions. Rabbits immunized actively or passively to alpha-toxin had reduced SLE scores (P <or= 0.0003 and P <or= 0.0033, respectively) and no epithelial erosions when infected with strain Newman. Western blot analysis demonstrated that strains Newman and Newman Delta(hlg), but not Newman Delta(hla), produced alpha-toxin. CONCLUSIONS: These results illustrate that the virulence of strain Newman involves both alpha- and gamma-toxin, with alpha-toxin mediating corneal epithelial erosions. An additional uncharacterized toxin could also be active in damaging the cornea.

Animals↗

PubMed2002

Effect of immunosuppression on gene expression in the HSV-1 latently infected mouse trigeminal ganglion.

PURPOSE: To determine alterations in expression of genes in herpes simples virus (HSV)-1 latently infected mouse trigeminal ganglia (TGs), after treatment with cyclophosphamide and dexamethasone. METHODS: Scarified corneas of female BALB/c mice were inoculated with HSV-1 strain McKrae. Four weeks after inoculation, cyclophosphamide and dexamethasone were intravenously injected to induce HSV-1 reactivation. Uninfected mice were also treated with the immunosuppressants. Four groups of animals were studied: uninfected, not treated; uninfected, drug treated; latently infected, not treated; and latently infected, drug treated. PolyA+ mRNA from the TGs of each group was reverse transcribed, labeled with 32P, incubated on a 1185-gene array membrane, and analyzed by phosphorimaging. As a comparison and to confirm microarray results, semiquantitative RT-PCR was also performed for selected genes. RESULTS: The immunosuppressive drugs significantly increased expression of two genes (calpactin 1 light chain and guanine nucleotide-binding protein alpha-stimulating polypeptide [GNAS]) in the ganglia of uninfected mice compared with those in untreated uninfected mice. Ten genes were shown to be significantly increased in the latent TGs of mice treated with immunosuppressants compared with latently infected untreated mice. These genes were prostaglandin E2 receptor EP4 subtype (PTGER4), insulin promoter factor 1 (IPF1), glutathione S-transferase mu2, cyclin D2, peripherin, plasma glutathione peroxidase, methyl CpG-binding protein 2, retinal S-antigen, ErbB2 proto-oncogene, and GNAS. Eight genes were shown to be significantly decreased in the HSV-1 latent TGs treated with the drugs, compared with untreated latently infected mice. These genes were peripheral myelin protein 22, decorin, transcription factor AP-1, dystroglycan 1, myelin protein zero, mitogen-activated protein kinase 3, prothymosin beta 4, and brain lipid-binding protein. The results obtained by semiquantitative RT-PCR were similar to those obtained by microarray analysis. CONCLUSIONS: Those genes with expression altered by immunosuppressive drug treatment may play an important role in ocular HSV-1 recurrence. Changes in expression of genes in the prostaglandin pathway, a transcription factor, and an enzyme in the cell cycle are considered especially important in HSV-1 reactivation by immunosuppression and are reviewed.

Animals↗

PubMed2002

Peripapillary scleral thickness in perfusion-fixed normal monkey eyes.

PURPOSE: To characterize the thickness of the peripapillary sclera in perfusion-fixed normal monkey eyes so as to build accurate computational models of intraocular pressure (IOP)-related stress and strain within these tissues. METHODS: Nine rhesus monkeys were perfusion fixed, each with one normal eye set to an IOP of 10 mm Hg by manometer. A 6-mm-diameter specimen containing the optic nerve head and peripapillary sclera was trephined from each scleral shell and cut into 4-microm serial sagittal sections across the scleral canal opening, either horizontally (four eyes) or vertically (five eyes). The thickness of the peripapillary sclera was measured on every 24th section at 100-microm intervals from the posterior scleral canal opening (PSCO) to the peripheral edge of the specimen. The data were pooled by quadrant (superior, inferior, nasal, and temporal), regions within each quadrant, and distance from the PSCO, overall and for individual eyes, and subjected to analysis of variance. RESULTS: In terms of distance from the PSCO, the peripapillary sclera was thinnest nearest the PSCO (201 microm, nasal; 201 microm, temporal; 240 microm, inferior; 249 microm, superior), thickened progressively to a maximum in the midperiphery approximately 600 to 1000 microm from the PSCO (326 microm, nasal; 415 microm, superior; 420 microm, temporal; 422 microm, inferior), and thinned again peripherally in all quadrants. The peripapillary sclera was thinner in the nasal quadrant when compared with the other quadrants superiorly, inferiorly, and temporally (central region means of 291 microm, nasal; 369 microm, superior; 372 microm, inferior; and 369 microm, temporal; P < 0.0001). CONCLUSIONS: In the normal monkey eye, peripapillary scleral thickness varies significantly with distance from the posterior scleral canal opening and is thinner in the nasal quadrant than in the other quadrants. These differences are substantial and are likely to affect the magnitude of IOP-related stress and strain within these tissues for a given level of IOP.

Animals↗

PubMedDate not supplied

Using dependency/association rules to find indications for computed tomography in a head trauma dataset.

Analysis of a clinical head trauma dataset was aided by the use of a new, binary-based data mining technique, termed Boolean analyzer (BA), which finds dependency/association rules. With initial guidance from a domain user or domain expert, the BA algorithm is given one or more metrics to partition the entire dataset. The weighted rules are in the form of Boolean expressions. To augment the analysis of the rules produced, we applied a probabilistic interestingness measure (PIM) to order the generated rules based on event dependency, where events are combinations of primed and unprimed variables. Interpretation of the dependency rules generated on the clinical head trauma data resulted in a set of criteria that identified minor head trauma patients needing computed tomography (CT) scans. The BA criteria contained fewer variables than were found using recursive partitioning of Chi-square values (five variables versus seven variables, respectively). The BA five-variable criteria set was more sensitive but less specific than the seven-variable Chi-square criteria set. We believe that the BA method has broad applicability in the medical domain, and hope that this paper will stimulate other creative applications of the technique.

Algorithms↗