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Biomedical subjects

J M Seddon

Publications and source records attributed to J M Seddon.

At least 37 records · Page 2Linked to original sources
PubMed2000

Patterns of tumor initiation in choroidal melanoma.

This study attempts to document the occurrence of tumors with respect to clock hour location and distance from the macula and to evaluate tumor location in relation to retinal topography and light dose distribution on the retinal sphere. Analysis of patterns of tumor initiation may provide new evidence to clarify the controversy regarding the possible light-related etiology of choroidal melanoma. Incident cases of choroidal and ciliary body melanoma in Massachusetts residents diagnosed between 1984 and 1993 were the basis for analysis. Conventional fundus drawings and photos were used to assess the initiation site of each tumor. The initiation site was defined as the intersect between the largest tumor diameter and the largest perpendicular diameter of the tumor. Initiation sites were recorded using spherical coordinates. The retinal sphere was divided into 61 mutually exclusive sectors defined according to clock hour and anteroposterior distance from the macula. Rates of initiation were computed for each sector, overall, and according to gender and other clinical factors. Results were similar in left and right eyes; therefore, these were combined in analysis. Tumor initiation had a predilection for the macula (P < 0.0001). Overall, no significant clock hour preference was observed (P = 0.63). However, the parafoveal zone showed a strong circular trend (P < 0.01), with highest rates occurring in the temporal region, and the lowest rates occurring in the nasal region. Rates of occurrence in six progressively more anterior concentric zones (designated as the foveal, parafoveal, posterior, peripheral, anterior, and ciliary body zones) were 21.4, 14.2, 12.1, 8.9, 4.5, and 4.3 counts per spherical unit per 1000 eyes, respectively. Concentric zone location did not vary by gender (P = 0.93) or laterality (P = 0.78). However, posterior location was associated with light iris color (P = 0.01). Tumor diameters were largest in the peripheral region of the fundus and smallest in the macular and ciliary body zone (P < 0.001). Clock hour location was not influenced by gender (P = 0.74), laterality (P = 0.53), iris color (P = 0.84), or tumor diameter (P = 0.73). Results suggest that tumor initiation is not uniformly distributed, with rates of occurrence concentrated in the macular area and decreasing monotonically with distance from the macula to the ciliary body. This pattern is consistent with the retinal topography and correlates positively with the dose distribution of solar light on the retinal sphere.

Aged↗
PubMed2000

Prospective study of alcohol consumption and the risk of age-related macular degeneration.

OBJECTIVE: To describe the relationship between alcohol consumption and the incidence of age-related macular degeneration (AMD). METHODS: We conducted a prospective study among female nurses between 1980 and 1994 and among male health professionals between 1986 and 1994. We included 32764 women and 29488 men who were 50 years or older, without a diagnosis of AMD or cancer at baseline, and added additional subjects to the analysis as they reached 50 years of age. Their alcohol intake was assessed at baseline and updated during follow-up evaluations using a validated semiquantitative food-frequency questionnaire. After separate analyses for women and men, pooled estimates of the relationship of alcohol to the risk of AMD were calculated. RESULTS: Age-related macular degeneration associated with a visual acuity loss of 20/30 or worse, including the early and dry and wet types, was diagnosed in 298 women (from 697498 person-years of follow-up) and 153 men (229 180 person-years) by 1994, the end of follow-up. After controlling for age, smoking, and other risk factors, the pooled relative risks (RRs) and 95% confidence intervals (CIs) for AMD compared with nondrinkers were 1.0 (0.7-1.2) for drinkers who consumed 0.1 to 4.9 g/d of alcohol; 0.9 (0.6-1.4) for 5 to 14.9 g/d; 1.1 (0.7-1.7) for 15 to 29.9 g/d; and 1.3 (0.9-1.8) for 30 g/d or more. Among women, there was a suggestion of a modest increased risk of the disease in drinkers who consumed 30 g/d or more (RR, 1.5; 95% CI, 1.0-2.4); this was limited to an increased risk of the early and dry form (RR, 2.0; 95% CI, 1.2-3.4). No specific type of alcohol provided protection against AMD. CONCLUSION: This prospective study does not support an inverse relationship between moderate alcohol consumption and risk of AMD.

Aged↗
PubMed2000

A randomized controlled trial of varying radiation doses in the treatment of choroidal melanoma.

OBJECTIVE: To determine if a reduction in proton radiation dose from the standard dose of 70 cobalt gray equivalents (CGE) to 50 CGE would decrease radiation-induced complications, thereby improving visual prognosis, without compromising local tumor control for patients with uveal melanoma at high risk of these complications. DESIGN: Randomized, double-masked clinical trial. PARTICIPANTS: A total of 188 patients with small or medium-sized choroidal melanomas (<15 mm in diameter and <5 mm in height) near the optic disc or macula (within 4 disc diameters of either structure). METHODS: Patients were treated with proton beam therapy at doses of either 50 CGE or 70 CGE between October 1989 and July 1994, and followed up biannually through April 1998. Outcomes included visual acuity, radiation complications, melanoma recurrence, and metastasis. RESULTS: Proportions of patients retaining visual acuity of at least 20/200 were similar in the 2 dose groups at 5 years after radiation (approximately 55%). Similar numbers of patients in each group experienced tumor regrowth (2 patients at 50 CGE vs 3 patients at 70 CGE; P>.99) and metastasis (7 patients at 50 CGE vs 8 patients at 70 CGE;P=.79). Five-year rates of radiation maculopathy also were similar (for both groups, approximately 75% for tumors within 1 disc diameter and 40% for tumors >1 disc diameter from the macula). Rates of radiation papillopathy were nonsignificantly decreased in the 50-CGE treatment group when tumors were located 1 disc diameter or less from the optic disc (P=.20). Patients treated with the lower dose also experienced significantly less visual field loss. CONCLUSIONS: This level of dose reduction did not result in a lesser degree of visual acuity loss. The lower-dose group did experience significantly less visual field loss. Local tumor recurrence and metastatic death rates were similar in both dose groups. Arch Ophthalmol. 2000;118:773-778

Adult↗
PubMed2000

A prospective study of alcohol consumption and cataract extraction among U.S. women.

PURPOSE: Alcohol consumption has been implicated in the pathogenesis of cataract in some, but not all analytic studies. To date, no prospective analysis of the relationship between alcohol consumption and cataract has been conducted in women. METHODS: We examined the association between alcohol consumption and cataract extraction in a prospective cohort of female registered nurses. In 1980, 50,461 women were included and others were added as they became 45 years of age for a total of 77,466 women. Information on alcohol consumption and incidence of senile cataract extraction was ascertained during 12 years of follow-up with biennial questionnaires. RESULTS: We observed 1468 cases of cataract extraction in 761,036 person-years of follow-up. Compared to nondrinkers, those consuming alcohol were not at increased risk of cataract, even up to 25 grams or more per day (2 or more drinks). Results remained unchanged after controlling for cataract risk factors including cigarette smoking, body mass index, and diabetes. When risk was examined for specific cataract subtypes only, those in the highest category of consumption had a multivariate relative risk of 1.10 for nuclear cataracts and 1.50 for posterior subcapsular cataracts only. CONCLUSIONS: These prospective data suggest that there is no substantial overall increased risk of senile cataract due to alcohol intake. The possibility that alcohol consumption leads to a modest increased risk of posterior subcapsular type opacities requiring extraction merits further exploration.

Adult↗
PubMed2000

Evaluating the effectiveness of a vision rehabilitation intervention using an objective and subjective measure of functional performance.

PURPOSE: To test the hypothesis that vision rehabilitation using optometry, occupational therapy and social work services increases patients' functional ability and to assess whether involving families in the intervention results in more successful outcomes. METHODS: We conducted an outcome study of 97 patients new to the Vision Rehabilitation Service. Subjects were between the ages of 19 and 91 years, with a median age of 76. Their visual acuities were 20/100 or worse in the better eye, with 50% of the subjects having acuities worse than 20/200. Macular degeneration was the most prevalent diagnosis. Subjects were assigned to either an individually focused (n=48) or a family focused (n=49) intervention. The outcome measure was change in function, as assessed by speed and accuracy of performance (objective measure) and by the patients' self-reports of difficulty and dependency in performing daily activities (subjective measures). Data were collected before and after the intervention. RESULTS: Most patients had documented improvement after rehabilitation on both objective (p=.0001) and subjective (decreased dependency, p=.01) measures of function. The sample size did not provide adequate statistical power to show differences between family focused and individually focused interventions. CONCLUSIONS: This study documents significant improvement after vision rehabilitation for a predominantly elderly population. Patients in both family and individually focused interventions improved comparably.

Activities of Daily Living↗
PubMed2000

Evolutionary lineages of RT1.Ba in the Australian Rattus.

In this study, the evolutionary history of the variable second exon of RT1.Ba and its adjoining intron b are compared across a number of species and subspecies of the Australian RATTUS: Three lineages are identified in the second intron across a range of Rattus species. Two of these lineages, separated by the insertion of a probable rodent short interspersed nucleotide element and by point mutations outside the indel region, are both found in each of the major clades of the endemic Australian RATTUS: This pattern of ancestral polymorphism is reflected in the adjoining exon 2 sequences, although phylogenetic constraints confirm that the clustering is not identical to that of the associated intron sequences. In addition, the coding sequences show evidence of the retention of ancestral polymorphism, with identical exon sequences found in two divergent species, and some indication of gene conversion detected for the exon sequences.

Amino Acid Sequence↗
PubMed1999

The genetics of age-related macular degeneration.

Age-related macular degeneration (AMD) is increasingly recognized as a complex genetic disorder in which one or more genes contribute to an individual's susceptibility for developing the condition. Twin and family studies as well as population-based genetic epidemiologic methods have convincingly demonstrated the importance of genetics in AMD, though the extent of heritability, the number of genes involved, and the phenotypic and genetic heterogeneity of the condition remain unresolved. The extent to which other hereditary macular dystrophies such as Stargardts disease, familial radial drusen (malattia leventinese), Best's disease, and peripherin/RDS-related dystrophy are related to AMD remains unclear. Alzheimer's disease, another late onset, heterogeneous degenerative disorder of the central nervous system, offers a valuable model for identifying the issues that confront AMD genetics.

Apolipoproteins E↗
PubMed1999

Clinical course of macular holes: the Eye Disease Case-Control Study.

OBJECTIVE: To describe the clinical course of affected and unaffected eyes in patients with idiopathic macular holes. PATIENTS: Prospective study of patients with macular holes enrolled in the Eye Disease Case-Control Study. MAIN OUTCOME MEASURES: The best-corrected visual acuity at follow-up was compared with that at baseline. Changes in the macular holes, including increases in size or spontaneous regression, were assessed. The rates of development of new macular holes in fellow unaffected eyes were estimated. RESULTS: Of the 198 patients examined at baseline, 28 (14.1%) died before reevaluation. Of those who survived, 122 (71.8%) had a follow-up examination. Approximately 34% (34.4%) of all eyes with macular holes had an increase in the size of the macular hole. Forty-five percent of eyes had a decrease in visual acuity of 2 or more lines and 27.8%, of 3 or more lines; 40.9% remained stable, with a gain or loss of fewer than 2 lines. The rate of development of a new macular hole during follow-up in fellow eyes that were unaffected at baseline was 4.3% for 3 or fewer years of follow-up, 6.5% for 4 to 5 years of follow-up, and 7.1% for 6 or more years of follow-up. Spontaneous regression of the macular hole occurred in 3 (8.6%) of 35 patients with a follow-up interval of 6 or more years, whereas no regression occurred in patients with a shorter follow-up. CONCLUSIONS: The visual acuity of 45.0% of eyes with macular holes deteriorated by 2 or more lines during follow-up. The rate of development of macular holes in unaffected fellow eyes was low.

Adult↗
PubMed1999

Evaluation of the Best disease gene in patients with age-related macular degeneration and other maculopathies.

Vitelliform macular dystrophy (VMD2, Best disease, MIM153700) is an early onset, autosomal, dominant macular degeneration characterized by the deposition of lipofuscin-like material within and below the retinal pigment epithelium (RPE); it is associated with degeneration of the RPE and overlying photoreceptors. Recently, we cloned the gene bestrophin, which is responsible for the disease, and identified a number of causative mutations in families with VMD2. Here, we report that the analysis of bestrophin in a collection of 259 age-related macular degeneration (AMD) patients provides evidence that mutations in the Best disease gene do not play a significant role in the predisposition of individuals to AMD. However, our results suggest that, in addition to Best disease, mutations within the bestrophin gene could be responsible for other forms of maculopathy with phenotypic characteristics similar to Best disease and for other diseases not included in the VMD category.

Adult↗
PubMed1999

Influence of age-related maculopathy on visual functioning and health-related quality of life.

PURPOSE: To describe the influence of age-related maculopathy on visual functioning and health-related quality of life. METHODS: A prospective, cross-sectional, observational cohort sample of 201 persons with various stages of age-related maculopathy was recruited from the Massachusetts Eye and Ear Infirmary as part of a longitudinal study of age-related macular degeneration. Persons were considered to have age-related maculopathy if one or more of the following clinical characteristics were present: drusen, retinal pigment epithelial changes, geographic atrophy, or evidence of exudative disease. Median corrected visual acuity for this sample was 20/25 in the better eye, with all subjects having 20/200 or better visual acuity in at least one eye at baseline. All participants underwent a comprehensive ophthalmologic examination with a dilated pupil. In addition to the usual clinical data collection, severity of age-related maculopathy was graded by an ophthalmologist who used standard clinical criteria and was masked to the participants' descriptions of visual functioning and health-related quality of life. All participants completed an interview that included the Activities of Daily Vision Scale, a survey designed to assess difficulties with routine daily activities that require vision, and the Short Form-36 Health Survey, a generic measure of multidimensional health-related quality of life. RESULTS: Severity of age-related maculopathy was associated with poorer scores of the Activities of Daily Vision Scale. This association was most significant for near vision and driving activities. In this sample, the SF-36 Health Survey scales were not significantly correlated with severity of age-related maculopathy. CONCLUSIONS: Reported visual functioning is significantly associated with the clinical severity of age-related maculopathy. However, once visual acuity is taken into consideration, clinical grading of age-related maculopathy did not explain a significant portion of the variation in visual functioning. The lack of significant correlation between severity of age-related maculopathy and the SF-36 Health Survey may have resulted from the small number of participants in our sample with severe bilateral age-related maculopathy.

Activities of Daily Living↗
PubMed1999

Variation on islands: major histocompatibility complex (Mhc) polymorphism in populations of the Australian bush rat.

Loss of genetic variation in small, isolated populations is commonly observed at neutral or nearly neutral loci. In this study, the loss of genetic variation was assessed in island populations for a locus of major histocompatibility complex (Mhc), a locus shown to be under the influence of balancing selection. A total of 36 alleles was found at the second exon of RT1.Ba in 14 island and two mainland populations of Rattus fuscipes greyii. Despite this high overall diversity, a substantial lack of variation was observed in the small island populations, with 13 islands supporting only one to two alleles. Two populations, Waldegrave and Williams Islands, showed moderately high levels of heterozygosity (52-56%) which were greater than expected under neutrality, suggesting the action of balancing selection. However, congruence between the level of variation at this Mhc locus and in previous allozyme electrophoresis and mitochondrial DNA studies highlights the dominant influence of genetic drift and population factors, such as bottlenecks and structuring in the founding population, in the loss of genetic variation in these small, isolated populations.

Animals↗
PubMed1999

Do age-related macular degeneration and cardiovascular disease share common antecedents?

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss and blindness in elderly Americans. The etiology of this condition remains unknown and treatment options are limited. Some epidemiological findings point to a cardiovascular risk profile among persons with AMD. Documented risk factors for cardiovascular disease (such as age, smoking, hypertension, hypercholesterolemia, post-menopausal estrogen use, diabetes, and dietary intake of fats, alcohol and antioxidants) have also been associated with AMD in some studies. This raises the possibility that the causal pathways for cardiovascular disease and AMD may share similar risk factors. Future research on this hypothesis could lead to important insights into etiologic factors for AMD. Research could also identify modifiable risk factors and suggest new treatment options which could prevent AMD, slow its progression, or reduce visual loss. Susceptible individuals could then be targeted for improved health promotion and disease prevention measures for this disabling and highly prevalent disorder.

Aging↗
PubMed1999

A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in US women.

BACKGROUND: Oxidation of lens proteins plays a central role in the formation of age-related cataracts, suggesting that dietary antioxidants may play a role in prevention. However, the relation between specific antioxidants and risk of cataract remains uncertain. OBJECTIVE: Our objective was to examine prospectively the association between carotenoid and vitamin A intakes and cataract extraction in women. METHODS: A prospective cohort of registered female nurses aged 45-71 y and free of diagnosed cancer was followed; in 1980, 50461 were included and others were added as they became 45 y of age for a total of 77466. Information on nutrient intake was assessed by repeated administration of a food-frequency questionnaire during 12 y of follow-up. RESULTS: During 761762 person-years of follow-up, 1471 cataracts were extracted. After age, smoking, and other potential cataract risk factors were controlled for, those with the highest intake of lutein and zeaxanthin had a 22% decreased risk of cataract extraction compared with those in the lowest quintile (relative risk: 0.78; 95% CI: 0.63, 0.95; P for trend = 0.04). Other carotenoids (alpha-carotene, beta-carotene, lycopene, and beta-cryptoxanthin), vitamin A, and retinol were not associated with cataract in multivariate analysis. Increasing frequency of intakes of spinach and kale, foods rich in lutein, was associated with a moderate decrease in risk of cataract. CONCLUSIONS: Lutein and zeaxanthin and foods rich in these carotenoids may decrease the risk of cataracts severe enough to require extraction.

Adolescent↗
PubMed1999

A prospective study of carotenoid intake and risk of cataract extraction in US men.

BACKGROUND: Dietary antioxidants, including carotenoids, are hypothesized to decrease the risk of age-related cataracts by preventing oxidation of proteins or lipids within the lens. However, prospective epidemiologic data concerning this phenomenon are limited. OBJECTIVE: Our objective was to examine prospectively the association between carotenoid and vitamin A intakes and cataract extraction in men. DESIGN: US male health professionals (n = 36644) who were 45-75 y of age in 1986 were included in this prospective cohort study. Others were subsequently included as they became 45 y of age. A detailed dietary questionnaire was used to assess intake of carotenoids and other nutrients. During 8 y of follow-up, 840 cases of senile cataract extraction were documented. RESULTS: We observed a modestly lower risk of cataract extraction in men with higher intakes of lutein and zeaxanthin but not of other carotenoids (alpha-carotene, beta-carotene, lycopene, and beta-cryptoxanthin) or vitamin A after other potential risk factors, including age and smoking, were controlled for. Men in the highest fifth of lutein and zeaxanthin intake had a 19% lower risk of cataract relative to men in the lowest fifth (relative risk: 0.81; 95% CI: 0.65, 1.01; P for trend = 0.03). Among specific foods high in carotenoids, broccoli and spinach were most consistently associated with a lower risk of cataract. CONCLUSIONS: Lutein and zeaxanthin may decrease the risk of cataracts severe enough to require extraction, although this relation appears modest in magnitude. The present findings add support for recommendations to consume vegetables and fruit high in carotenoids daily.

Adult↗
PubMed1999

A prospective study of vitamin supplement intake and cataract extraction among U.S. women.

We prospectively examined the association between vitamin supplement intake and the incidence of cataract extraction during 12 years of follow-up in a cohort of 47,152 female nurses. Women were 45 years or older and free of diagnosed cancer in 1980; others were added as they reached 45 years of age, for a total of 73,956 women. During 720,082 years of follow-up, 1,377 senile cataracts were diagnosed and extracted. Those who used multivitamins or separate supplements of vitamin C, E, or A did not have decreased risks of cataract as compared with nonusers even for use of 10 or more years. After adjusting for cataract risk factors, including cigarette smoking, body mass index, and diabetes mellitus, users of vitamin C supplements for 10 or more years had a relative risk (RR) of 0.95 [95% confidence interval (CI) = 0.76-1.20]. Associations were stronger among long-term vitamin C supplement users who were never-smokers (RR = 0.71; 95% CI = 0.47-1.08) and less than 60 years of age (RR = 0.72; 95% CI = 0.49-1.04). These findings suggest that there is little overall benefit of long-term use of vitamin supplements for risk of cataracts requiring extraction.

Adult↗
PubMed1998

The rate of mitochondrial 12S rRNA gene evolution is similar in freshwater turtles and marsupials.

Assertions that the "conventional" rate of mitochondrial DNA (mtDNA) evolution is reduced in poikilotherms in general and turtles in particular were tested for side-necked turtles (Pleurodira: Chelidae). Homologous data sets of mitochondrial 12S rRNA gene sequences were used to compare the average divergence between the Australian and South American species for two Gondwanan groups: the chelid turtles and the marsupials. The mean nucleotide divergences between continental groups for both the turtles and the marsupials are remarkably similar. These data suggest that the rate of evolution of mitochondrial 12S rRNA gene is not substantially slower in turtles than in the homeothermic marsupials.

Animals↗