Biomedical subjects

Frank Billson

Publications and source records attributed to Frank Billson.

8 recordsLinked to original sources

PubMed2006

Deletion at 14q22-23 indicates a contiguous gene syndrome comprising anophthalmia, pituitary hypoplasia, and ear anomalies.

Anophthalmia and pituitary gland hypoplasia are both debilitating conditions where the underlying genetic defect is unknown in the majority of cases. We identified a patient with bilateral anophthalmia and absence of the optic nerves, chiasm and tracts, as well as pituitary gland hypoplasia and ear anomalies with a de novo apparently balanced chromosomal translocation, 46,XY,t(3;14)(q28;q23.2). Translocation breakpoint analysis using FISH and high-resolution microarray comparative genomic hybridization (CGH) has identified a 9.66 Mb deleted region on the long arm of chromosome 14 which includes the genes BMP4, OTX2, RTN1, SIX6, SIX1, and SIX4. Three other patients with interstitial deletions involving 14q22-23 have been described, all with bilateral anophthalmia, pituitary abnormalities, ear anomalies, and a facial phenotype similar to our patient. OTX2 is involved in ocular developmental defects, and the severity of the ocular phenotype in our patient and the other 14q22-23 deletion patients, suggests this genomic region harbors other gene/s involved in ocular development. BMP4 haploinsufficiency is predicted to contribute to the ocular phenotype on the basis of its expression pattern and observed murine mutant phenotypes. In addition, deletion of BMP4 and SIX6 is likely to contribute to the abnormal pituitary development, and SIX1 deletion may contribute to the ear and other craniofacial features. This indicates that contiguous gene deletion may contribute to the phenotypic features in the 14q22-23 deletion patients.

Abnormalities, Multiple↗

PubMed2005

Paroxysmal tonic upgaze of childhood--a review.

Ouvrier and Billson (1988) were apparently the first to describe this entity. In the four original cases, the clinical features were as follows: (1) onset usually under 1 year of age, (2) episodes of variably sustained conjugate upward deviation of the eyes, with neck flexion (chin down) apparently compensating for the abnormal eye position, (3) downbeating saccades in attempted downgaze, (4) normal horizontal eye movements, (5) diurnal fluctuation of symptoms, (6) frequent relief by sleep, (7) exacerbation with febrile illnesses, (8) varying degrees of ataxia, (9) neurological examination usually otherwise normal, (10) absence of deterioration during long-term follow-up, (11) eventual improvement, (12) usually negative investigations, including imaging, EEG and CSF neurotransmitters. As of 2002, 49 cases have been reported. Aetiological factors have included autosomal dominant inheritance in four families, foetal exposure to sodium valproate in three cases, and structural lesions in five (hypomyelination x 2, periventricular leukomalacia, Vein of Galen malformation, pinealoma). Only a few cases have responded to L-dopa. The pathophysiology is still not understood. The outcome appears to be good in about half the cases. Ataxia, borderline cognitive abilities and residual minor oculomotor disorders are seen in the remainder.

Diagnosis, Differential↗

PubMed2005

Effect of fixation tasks on multifocal visual evoked potentials.

PURPOSE: This study investigated the effects of cognitive influence on the multifocal visual evoked potential (mVEP) at different levels of eccentricity. Three different foveal fixation conditions were utilized involving varying levels of task complexity. A more complex visual fixation task has been known to suppress peripheral signals in subjective testing. METHODS: Twenty normal subjects had monocular mVEPs recorded using the AccuMap objective perimeter. This allowed simultaneous stimulation of 58 segments of the visual field to an eccentricity of 24 degrees. The mVEP was recorded using three different fixation conditions in random order. During task 1 the subject passively viewed the central fixation area. For task 2 alternating numbers were displayed within the fixation area; the subject on viewing the number '3' in the central fixation area indicated recognition by pressing a button. Throughout task 3, numbers were displayed as in task 2. The subject had the cognitive task of summating all the numbers. RESULTS: Analysis revealed that the increased attention and concentration demanded by tasks 2 and 3 in comparison with task 1 resulted in significantly enhanced central amplitudes of 9.41% (Mann-Whitney P = 0.0002) and 13.45% (P = 0.0002), respectively. These amplitudes became reduced in the periphery and approached those of task 1, resulting in no significant difference between the three tasks. Latencies demonstrated no significant difference between each task nor at any eccentricity (P > 0.05). As the complexity of each task increased the amount of alpha rhythm was significantly reduced. CONCLUSIONS: Our findings indicate that task 1 required a minimal demand of cognition and was associated with the greatest amount of alpha rhythm. It was also the most difficult to perform because of loss of interest. The other two tasks required a greater demand of higher order cognitive skills resulting in significantly enhanced amplitudes centrally and the attenuation of alpha rhythm. Therefore, amplitudes are increased around the area of attention.

Adult↗

PubMed2005

The interaction of indocyanine green with human retinal pigment epithelium.

PURPOSE: This study sought to examine the in vitro interaction of human RPE cells with indocyanine green (ICG). The interaction between ICG and the RPE may have clinical relevance in the interpretation of clinical ICG angiography. METHOD: Cultured primary human RPE cells were incubated with ICG. Infrared fluorescence microscopy was used to detect RPE cell ICG fluorescence. The proportions of cells exhibiting ICG infrared fluorescence were quantified. Separate RPE cell populations were incubated with ouabain for 24 and 72 hours, respectively, before addition of the ICG to examine its effect on the uptake of ICG. The effect of ouabain on cell viability was assessed with trypan blue exclusion. RESULTS: Normal human RPE cells incubated with ICG exhibited strong infrared fluorescence. Exposure to ouabain for 24 hours before incubation with ICG had little effect on cell viability but significantly reduced cellular ICG fluorescence. In contrast, exposure to ouabain for 72 hours reduced cell viability and increased cellular ICG fluorescence. CONCLUSIONS: Cultured human RPE cells take up ICG dye. ICG uptake by RPE cells may involve active transport, as cells incubated with ouabain for 24 hours showed no reduction in cell viability but exhibited reduced infrared fluorescence. The paradoxical increased uptake of ICG into the cells after more prolonged exposure to ouabain may be due to ICG's movement through the damaged cell membrane. Fluorescence due to ICG uptake by RPE has clinical relevance in that it contributes to the fluorescence patterns observed in ICG angiography.

Biological Transport, Active↗

PubMed2004

Neurofibromatosis type 1 and optic pathway gliomas: follow-up of 54 patients.

OBJECTIVE: To describe the natural history of optic pathway gliomas (OPGs) in patients with neurofibromatosis type 1 (NF1), and to evaluate the current recommended guidelines for monitoring and follow-up of OPGs in this population. DESIGN: Retrospective case series. PARTICIPANTS: Patients with OPGs and NF1 seen in the neurofibromatosis clinic at the Children's Hospital at Westmead in Sydney, Australia. METHODS: Patients with definite NF1 and confirmed OPGs were identified and their medical records searched to obtain data on demographics, details of the OPG diagnosis, and serial ophthalmic examination findings. Patients were stratified into groups according to age and mode of presentation. MAIN OUTCOME MEASURES: Visual acuity was recorded for each eye and grouped into mild (Snellen equivalent > or = 6/12), moderate (Snellen equivalent = 6/15-6/60), and severe (Snellen equivalent < 6/60) visual impairment at time of diagnosis, during follow-up, and at the most recent examination. RESULTS: Data were collected on 54 patients, the majority of whom (78%) were seen from 1990 to 2002, with an average follow-up of 8.6 years. The mean age at the time of OPG diagnosis was 5.2 years, with 32 patients having symptoms or signs at the time of diagnosis. Seventeen patients were diagnosed after the age of 6 years (range, 7-15). Twenty-two patients had tumor progression within 1 year of diagnosis, and a further 6 patients showed progression after 1 year. Most patients' conditions were managed conservatively (68.5%). At follow-up, 17 patients (31.5%) had severe visual impairment (<6/60 Snellen equivalent) in their worse eye, and 16.7% had bilateral moderate/severe visual impairment. CONCLUSIONS: Contrary to some previous reports, our results show that OPGs in patients with NF1 often present in older children and may progress some time after diagnosis. Given the potential for serious visual consequences, these findings indicate a need for regular ophthalmological monitoring of this population for a long duration.

Adolescent↗

PubMed2004

Effect of check size and stimulation rate on blue-yellow multifocal visual evoked potentials.

BACKGROUND: To determine the effect of different stimulus frame rates and check sizes on blue-yellow multifocal visual evoked potentials (mVEP). METHODS: Subjects were examined at the Save Sight Institute at the University Sydney. Experiment 1 involved five adult subjects who underwent binocular stimulation by the Accumap multifocal objective perimeter. The eyes were stimulated with a cortically scaled dartboard pattern consisting of isoluminant blue and yellow checks. These were arranged in three concentric rings extending to an eccentricity of 26 degrees in the visual field. The stimulus pattern was driven by binary sequences resulting in pseudorandom binary exchange of two opposite checkerboard patterns at each of the 32 sites in the visual field. The mVEP were recorded at two different rates of display of the pattern stimulus. In experiment 2, mVEP were tested on 10 normal subjects. Each of the 36 stimulation sites contained a checkerboard pattern of 20, 30, 42 or 56 checks/site, the stimulation pattern was displayed at the optimum rate found in experiment 1. The size of the checks was inversely proportional to the number of checks per site. RESULTS: In experiment 1, the slow frame rate significantly increased the average amplitude throughout the field tested by 50 +/- 10.1% (P = 0.001). Latency was significantly shortened by 6.3% (P < 0.01). In experiment 2, the average amplitude peaked at 30 checks per segment; however, this was only calculated to be significantly different from the smallest check size (F(crit range 4,27) = 0.09 P < 0.05, anova, Tukey's T method). A similar difference was found in ring 1 (F(crit range 4,27) = 0.09, P < 0.05, anova, Tukey's T method). In ring 2, however, there was also a significant difference between 56 checks and 20, 30 and 42 (F(crit range 4,27) = 0.09, anova, P < 0.05). Altering the check sizes did not significantly affect the amplitudes in ring 3. The latencies were not significantly modified by altering check size at any eccentricity. CONCLUSIONS: These findings suggest that slowing the stimulation rate and displaying 30 checks per stimulation segment optimizes the blue-yellow mVEP stimulus.

Adult↗

PubMed2003

A randomized clinical trial of a single dose of intravitreal triamcinolone acetonide for neovascular age-related macular degeneration: one-year results.

OBJECTIVE: To determine if a single intravitreal injection of 4 mg of triamcinolone acetonide in patients with classic choroidal neovascularization associated with age-related macular degeneration can safely reduce the risk of severe visual loss. METHODS: A double-masked, placebo-controlled, randomized clinical trial was performed in patients 60 years or older who had choroidal neovascularization with any classic component, a duration of symptoms of less than 1 year, and a visual acuity of 20/200 or better. Best-corrected visual acuity, intraocular pressure, and cataract grading were performed before the injection and then at 3, 6, and 12 months. MAIN OUTCOME MEASURE: The development of severe loss of vision (30 letters) by survival analysis on an intention-to-treat basis. RESULTS: One hundred fifty-one eyes were randomized into the study, and follow-up data were obtained for 73 (97%) of the 75 eyes in the treated group and for 70 (92%) of the 76 eyes in the control group. There was no difference between the 2 groups for the development of severe visual loss during the first year of the study (log-rank chi 2(1) = 0.03, P =.90). In both groups, the 12-month risk of severe visual loss was 35%, with a hazard ratio of 1.05 (95% confidence interval, 0.59-1.86). The change in size of the neovascular membranes, however, was significantly less in eyes receiving triamcinolone than in those receiving placebo 3 months after treatment (P =.01), although no difference was noted after 12 months. After 12 months, treated eyes had a significantly higher risk of an elevated intraocular pressure (31/75 [41%] vs 3/76 [4%]; P<.001), but not of cataract progression (P =.29). CONCLUSIONS: A single dose of intravitreal triamcinolone had no effect on the risk of loss of visual acuity during the first year of the study in eyes with age-related macular degeneration and classic choroidal neovascularization, despite a significant antiangiogenic effect found 3 months after treatment. This biological effect warrants further study.

Aged↗

PubMed2003

Systemic use of anti-inflammatory medications and age-related maculopathy: the Blue Mountains Eye Study.

PURPOSE: To assess whether an association exists between systemic use of anti-inflammatory medications at baseline and the prevalence or incidence of either late or early age-related maculopathy (ARM) in a population-based cohort. METHODS: 3654 participants of the Blue Mountains Eye Study baseline examination (1992-94) were followed during 1997-99. Use of anti-inflammatory medication was recorded during the baseline interview. After excluding 543 persons who died since baseline, 2334 (75% of the surviving participants) attended 5-year follow-up examinations. Retinal photographs taken during both examinations were graded using the Wisconsin Age-Related Maculopathy Grading System. Prevalence refers to the proportion of participants having ARM at baseline. Incidence refers to the proportion of participants without ARM at baseline who developed it over the 5-year period. Known ARM risk factors were adjusted for when assessing the relationship between use of anti-inflammatory medications and ARM. RESULTS: At baseline, 1010 (27.6%) of 3654 participants were current users of non-steroidal anti-inflammatory drugs (NSAIDs), 514 (14.1%) were past users and 1282 (35.1%) were ever users. The corresponding numbers of subjects reporting current, past or ever use of corticosteroids (including inhaled steroids) were 225 (6.2%), 519 (14.2) and 564 (15.4), respectively. Late ARM was present in 72 participants (2.0%) and early ARM was present in 171 participants (4.9%) at the baseline examination. During the follow-up period, 25 participants (1.1%) developed incident late ARM and 192 (8.7%) developed incident early ARM. After adjusting for age, sex, family history of ARM and smoking, no significant associations were evident for the use of NSAIDs or corticosteroids and the prevalence of either late or early ARM. There were also no associations found between use of these medications at baseline and the 5-year incidence of either late or early ARM. CONCLUSIONS: No association was found between use of systemic anti-inflammatory medications and either the cross-sectional prevalence or longitudinal incidence of ARM in this population.

Aged↗