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Biomedical subjects

J M Seddon

Publications and source records attributed to J M Seddon.

At least 55 records · Page 3Linked to original sources
PubMed1998

Risk factors for hemiretinal vein occlusion: comparison with risk factors for central and branch retinal vein occlusion: the eye disease case-control study.

OBJECTIVE: Possible risk factors for hemiretinal vein occlusion were identified and compared with risk factor profiles for central and branch retinal vein occlusion. DESIGN: The design was a multicenter case-control study. METHODS: The authors identified 79 patients with hemiretinal vein occlusion (HRVO), 258 patients with central retinal vein occlusion (CRVO), 270 patients with branch retinal vein occlusion (BRVO), and 1142 control subjects at 5 clinical centers. Risk factor data were obtained through interviews, clinical examinations, and laboratory analyses of blood specimens. RESULTS: Systemic hypertension and history of diabetes mellitus were associated with increased risk of HRVO. Risk of CRVO increased with history of diabetes, systemic hypertension, and higher erythrocyte sedimentation rate (females only); risk of CRVO decreased with increasing amounts of physical activity and increasing amounts of alcohol consumption. Systemic hypertension, higher body mass index, and higher alpha2-globulin levels were associated with increased risk of BRVO, whereas higher high-density lipoprotein levels and increasing levels of alcohol consumption were associated with decreased risk of BRVO. Glaucoma history was associated with all three types of retinal vein occlusion. CONCLUSION: Patients presenting with retinal vein occlusion should be evaluated for cardiovascular disease, diabetes, and glaucoma.

Adult↗
PubMed1997

Cancer incidence after retinoblastoma. Radiation dose and sarcoma risk.

CONTEXT: There is a substantial risk of a second cancer for persons with hereditary retinoblastoma, which is enhanced by radiotherapy. OBJECTIVE: To examine long-term risk of new primary cancers in survivors of childhood retinoblastoma and quantify the role of radiotherapy in sarcoma development. DESIGN: Cohort incidence study of patients with retinoblastoma followed for a median of 20 years, and nested case-control study of a radiation dose-response relationship for bone and soft tissue sarcomas. SETTING/PARTICIPANTS: A total of 1604 patients with retinoblastoma who survived at least 1 year after diagnosis, identified from hospital records in Massachusetts and New York during 1914 to 1984. RESULTS: Incidence of subsequent cancers was statistically significantly elevated only in the 961 patients with hereditary retinoblastoma, in whom 190 cancers were diagnosed, vs 6.3 expected in the general population (relative risk [RR], 30 [95% confidence interval, 26-47]). Cumulative incidence (+/-SE) of a second cancer at 50 years after diagnosis was 51.0% (+/-6.2%) for hereditary retinoblastoma, and 5.0% (+/-3.0%) for nonhereditary retinoblastoma. All 114 sarcomas of diverse histologic types occurred in patients with hereditary retinoblastoma. For soft tissue sarcomas, the RRs showed a stepwise increase at all dose categories, and were statistically significant at 10 to 29.9 Gy and 30 to 59.9 Gy. A radiation risk for all sarcomas combined was evident at doses above 5 Gy, rising to 10.7-fold at doses of 60 Gy or greater (P<.05). CONCLUSIONS: Genetic predisposition has a substantial impact on risk of subsequent cancers in retinoblastoma patients, which is further increased by radiation treatment. A radiation dose-response relationship is demonstrated for all sarcomas and, for the first time in humans, for soft tissue sarcomas. Retinoblastoma patients should be examined for new cancers and followed into later life to determine whether their extraordinary cancer risk extends to common cancers of adulthood.

Adolescent↗
PubMed1997

Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of severe central visual impairment among the elderly and is associated both with environmental factors such as smoking and with genetic factors. Here, 167 unrelated AMD patients were screened for alterations in ABCR, a gene that encodes a retinal rod photoreceptor protein and is defective in Stargardt disease, a common hereditary form of macular dystrophy. Thirteen different AMD-associated alterations, both deletions and amino acid substitutions, were found in one allele of ABCR in 26 patients (16%). Identification of ABCR alterations will permit presymptomatic testing of high-risk individuals and may lead to earlier diagnosis of AMD and to new strategies for prevention and therapy.

ATP-Binding Cassette Transporters↗
PubMed1997

Phosphatidylcholine-fatty acid membranes: effects of headgroup hydration on the phase behaviour and structural parameters of the gel and inverse hexagonal (H(II)) phases.

The phase behaviour and structural parameters of a homologous series of saturated diacyl phosphatidylcholine/fatty acid 1:2 (mol/mol) mixtures having chain lengths from C12 to C20 were studied by X-ray diffraction and calorimetry, as a function of water content. The chain-melting transition temperatures of the 1:2 PC/FA mixtures are found to be largely independent of the degree of hydration. For all chain lengths, the tilted L(beta') and rippled P(beta') gel phases of the pure PC component are replaced by an untilted L(beta) gel phase in the 1:2 PC/FA mixtures. This gel phase swells considerably upon hydration, with a limiting water layer thickness in the range 18-24 A, depending on the chain length. However, unlike pure phospholipid systems, the lateral chain packing within the gel phase bilayers is essentially identical in both the dry and the fully hydrated states. The fluid bilayer L(alpha) phase is suppressed in the 1:2 mixtures, being replaced by inverse non-lamellar phases for all chain lengths greater than C12, and at all levels of hydration. For chain lengths of C16 and greater, the inverse hexagonal H(II) phase is formed directly upon chain melting, at all water contents. For the shorter chain length mixtures, the behaviour is more complex, with the H(II) phase forming at low hydration, but with bicontinuous cubic phases appearing at higher levels of hydration. The implications of these surprising results are explored, in terms of the effective hydrophilicity of the associated PC and FA headgroups and the packing within the interfacial region. We suggest that the presence of the fatty acids significantly alters the lateral stress profile across the lipid monolayer in the fluid state, compared to that of the corresponding pure PC system, such that inverse phases, where the interface bends towards the water, become strongly favoured. Furthermore, for short chain lengths, packing constraints favour the formation of phases with negative interfacial Gaussian curvature, such as the bicontinuous cubic phases, rather than the H(II) phase, which has more severe chain packing frustration.

Calorimetry↗
PubMed1997

Phylogenetic relationships of chelid turtles (Pleurodira: Chelidae) based on mitochondrial 12S rRNA gene sequence variation.

Conflicting phylogenies have been proposed for the Chelidae (Testudines: Pleurodira), a family of side-necked turtles found only in Australasia and South America. Sequence data from the mitochondrial 12S rRNA gene were used to test these phylogenies. In total, 411 nucleotides were sequenced for each of 16 chelid species, including all 11 recognized chelid genera and, as outgroups, 5 genera of Pelomedusidae (Testudines: Pleurodira). Analyses using parsimony and neighbor joining algorithms strongly support the division of Australian Chelidae into the three monophyletic groups initially suggested by Burbidge et al. (1974; Copeia 2: 392-409): Chelodina (bootstrap value 99%), the Emydura group (87%), and Pseudemydura. The analyses suggest that the Australian chelids are a monophyletic lineage (64%), with the Australian long-necked turtles, Chelodina, more closely related to the Australian short-necked chelids than to the long-necked South American species. These relationships are in contrast to those of Gaffney (1977; Am. Mus. Novitates 2620: 1-28). The species of Australian long-necked chelids consistently form a monophyletic clade, with Chelodina longicollis and Chelodina oblonga as sister taxa. The data failed to resolve relationships among the Australian short-necked taxa: Emydura, the Elseya latisternum group, the Elseya dentata group, Rheodytes, and Elusor. Unlike Gaffney (1977), we find some weak support (58%) for Pseudemydura as the closest relative of the other Australian short-necked taxa. With the exception of Hydromedusa, the South American taxa are monophyletic and the subgenera of Phrynops are paraphyletic.

Animals↗
PubMed1997

Phenotypic heterogeneity in families with age-related macular degeneration.

PURPOSE: To evaluate the ophthalmic phenotype in families with three or more individuals who have age-related maculopathy. METHODS: Eight families were identified at academic centers in Massachusetts and North Carolina. Macular findings were graded based on a modification of the grading system used in the Age-Related Eye Disease Study (AREDS). RESULTS: All families had at least three members with stage 3 (extensive drusen change) or higher maculopathy in at least one eye, and six families had at least two members with advanced maculopathy (stage 4, geographic atrophy of the retinal pigment epithelium, or stage 5, exudative maculopathy). Both stages 4 and 5 maculopathy were observed among different individuals in four families. Individuals with stage 3 maculopathy were members of families with more advanced maculopathy (six families) and were of similar age as more severely affected family members but tended to be older than those with stage 2. CONCLUSION: The phenotypic appearance of the macula in families with multiple affected individuals is heterogeneous and representative of the spectrum of macular findings typically associated with age-related maculopathy.

Adult↗
PubMed1997

Familial aggregation of age-related maculopathy.

PURPOSE: To determine whether age-related maculopathy aggregates in families by evaluating whether its prevalence is higher among relatives of case subjects with age-related maculopathy compared with relatives of control subjects without age-related maculopathy. METHODS: Individuals with (n = 119) and without (n = 72) age-related maculopathy were identified. First-degree relatives of case and control probands (parents, siblings, or offspring) 40 years of age or older were asked whether they had ever been diagnosed with macular degeneration. Medical records of 177 case and 146 control relatives confirmed the presence or absence of age-related maculopathy. RESULTS: The prevalence of medical-record confirmed age-related maculopathy was significantly higher among first-degree relatives of case probands (23.7%) compared with first-degree relatives of control probands (11.6%) with an age- and sex-adjusted odds ratio (OR), 2.4; 95% confidence interval (CI), 1.2 to 4.7; P = .013. Relatives of 78 case probands with exudative disease had a significantly higher prevalence of maculopathy (26.9%) compared with relatives of the 72 unaffected control probands (11.6%) (adjusted OR, 3.1; 95% CI, 1.5 to 6.7; P = .003), whereas the prevalence of age-related maculopathy among relatives of 41 probands with dry maculopathy (19.2%) was slightly but not significantly higher (adjusted OR, 1.5; 95% CI, 0.6 to 3.7; P = .36). CONCLUSIONS: The prevalence of age-related maculopathy among first-degree relatives of subjects with age-related maculopathy, particularly with exudative disease, is greater than among first-degree relatives of subjects without this disease. Results suggest that macular degeneration has a familial component and that genetic or shared environmental factors, or both, contribute to its development.

Adult↗
PubMed1997

Exclusion of TIMP3 as a candidate locus in age-related macular degeneration.

PURPOSE: Age-related macular degeneration (AMD) is a genetically complex disorder. Tissue inhibitor of metalloproteinases-3 (TIMP3) on chromosome 22 has been identified as a gene that is mutated in Sosby's fundus dystrophy, an autosomal-dominant macular dystrophy that phenotypically resembles AMD. The purpose of this study was to determine whether TIMP3 is a major susceptibility gene for the AMD phenotype. METHODS: Thirty-eight multiplex families with AMD were identified in Massachusetts and North Carolina. The macular findings were graded according to a modification of the grading system used in the Age-Related Eye Disease Study, and persons with extensive intermediate drusen, any large drusen, geographic atrophy, or evidence of exudative maculopathy were coded as affected for the purpose of the analysis. Linkage analysis was performed using both model-dependent (lod score) and model-independent (sibpair) methods. For the lod score analysis, both autosomal-dominant as well as recessive low penetrance "affecteds only" analyses were examined. Three markers, D22S280, D22S529, and D225268, linked tightly and flanking the TIMP3 locus, were chosen for the analysis. Association studies were performed by examining one randomly chosen affected person per family and comparing the patients with AMD with a series of age, gender, and ethnically matched control subjects with no known history of AMD. RESULTS: Lod score analysis excluded linkage in these data for an approximately 10-cm interval surrounding the TIMP3 gene for all models tested. In addition, no significant findings were observed with either the sibpair or the association study. CONCLUSIONS: No evidence of linkage or association or both was found between AMD and TIMP3 in these 38 families. These data suggest that although clinically similar, the genetic defect in Sorsby's fundus dystrophy is of a different cause than the majority of the genetic causes of AMD.

Aged↗
PubMed1996

A prospective study of cigarette smoking and age-related macular degeneration in women.

OBJECTIVE: To evaluate the relationship between cigarette smoking and incidence of age-related macular degeneration (AMD) among women. DESIGN: Prospective cohort study with 12 years of follow-up (1980 to 1992), in which information on smoking habits was updated every 2 years. SETTING: Eleven states throughout the United States. PARTICIPANTS: A total of 31 843 registered nurses enrolled in the Nurses' Health Study who were aged 50 to 59 years in 1980 and did not report a diagnosis of cancer or AMD at the beginning of the study. Additional women entered the analytic cohort as they reached 50 years of age. MAIN OUTCOME MEASURE: Incidence of AMD with visual loss. RESULTS: During 556 338 person-years of follow-up, 215 women were newly diagnosed as having AMD. After adjusting for other risk factors for AMD, women who currently smoked 25 or more cigarettes per day had a relative risk (RR) of AMD of 2.4 (95% confidence interval [CI], 1.4-4.0) compared with women who never smoked. Past smokers of this amount also had a 2-fold increased risk (RR=2.0; 95% CI, 1.2-3.4) relative to never smokers. Compared with current smokers, little reduction in risk was suggested even after quitting smoking for 15 or more years. Risk of AMD also increased with an increasing number of pack-years smoked (P for trend <.001); among women who smoked for 65 or more pack-years, the risk was 2.4 times the risk of never smokers (95% CI, 1.5-3.8). Analyses of dry and exudative types of AMD and other alternative definitions of AMD revealed similar results. CONCLUSIONS: Cigarette smoking is an independent and avoidable risk factor for AMD among women. Because AMD is the most common cause of severe visual impairment among the elderly and treatment is not available or is ineffective for most patients, reducing the risk of this disease is another important reason to avoid smoking.

Cohort Studies↗
PubMed1996

Freeze fracture electron microscopy of lyotropic lipid systems: quantitative analysis of the inverse micellar cubic phase of space group Fd3m (Q227).

An inverse micellar cubic phase of cubic aspect 15 formed by dioleoylglycerol/dioleoylphosphatidylcholine mixtures has been studied by freeze fracture electron microscopy. The structure was well preserved after freezing samples which had been hydrated either in pure water or in 30 vol% aqueous glycerol solutions. Electron microscopy images of high quality and resolution have been obtained. Four types of fracture planes, perpendicular to the [111], [110], [311] and [100] crystallographic axes, were identified by optical diffraction of the images from selected areas of the replicas. This is the largest number of different fracture planes yet observed in any lipid mesophase by electron microscopy. These planes are also perpendicular to the directions of the lowest order, and most intense reflections in the X-ray patterns from this cubic phase. The images were filtered using correlation averaging techniques, and they revealed the presence of mirror planes, which establishes that the space group is Fd3m (Q227) rather than Fd3. The interpretation of the images was aided by the novel use of standard deviation (s.d.) information obtained from the averaging procedures. The results are easily interpreted with the structure model deduced from X-ray diffraction and consisting of a complex packing of two different sizes of quasi-spherical inverse micelles located at positions (a) and (d) of the Fd3m unit cell. The results also show clearly that the fracture pathways always coincide with the regions of high CH3 concentration, located between the crystallographic planes containing the larger inverse micelles located at positions (a).

Diglycerides↗
PubMed1996

Decision-making in the treatment of subfoveal neovascularization in age-related macular degeneration. An analysis from the patient's perspective.

BACKGROUND: The clinical management of subfoveal neovascularization in age-related macular degeneration remains controversial. Large multicenter clinical trials recommend laser photocoagulation for certain subfoveal membranes, but many ophthalmologists are reluctant to treat patients with such lesions because a substantial initial visual loss may be induced by the treatment itself. Despite these controversies in management, the attitude of patients toward treatment of these lesions has not been assessed systematically. METHODS: In this article, a newly designed survey containing five hypothetical clinical scenarios was given to 68 patients with age-related macular degeneration to measure their relative preferences for the potential long-term benefits of laser photocoagulation compared with the immediate visual loss induced by laser therapy. RESULTS: This pilot study reveals a strong preference by these patients for laser intervention, despite the risk of immediate visual loss. On all five questions, the laser treatment outcome was preferred over the natural course of the disease. CONCLUSION: Ophthalmologists, when making clinical recommendations to patients with subfoveal exudative macular degeneration, may wish to consider the results of this survey, which suggest a substantial patient preference for laser treatment versus no intervention.

Aged↗
PubMed1995

Prediction of visual function after cataract surgery. A prospectively validated model.

OBJECTIVE: To develop a model to predict visual functional improvement after cataract extraction with intraocular lens implantation based on preoperative data. DESIGN: A prospective study with serial evaluations of visual function preoperatively and at 3 and 12 months after surgery. SETTING: The General Eye Service of the Massachusetts Eye and Ear Infirmary. Boston, Mass, and 33 ophthalmology practices in Boston. PATIENTS: Patients (N = 426; ages, > or = 65 years) who were undergoing cataract surgery. METHODS: Twelve-month improvement in visual function was measured by using the Activities of Daily Vision Scale (ADVS). Ordinal logistic regression was used to identify correlates of improved ADVS scores in 281 patients (derivative set). Potential factors included the preoperative visual acuity, preoperative ADVS score, four chronic ocular diseases, eight medical conditions, and demographic characteristics. Five predictors were identified and used to construct a prediction rule. The accuracy of the prediction rule was evaluated in an independent group of 145 patients (validation set). RESULTS: Postoperatively, 40% of the 281 patients in the derivative set had substantial improvement in their ADVS scores, and 53 (19%) had some improvement. Predictors of improvement included younger age (P < .001), a poorer preoperative ADVS score (P < .001), posterior subcapsular cataract (P = .09), and absence of age-related cataract (P = .09), and absence of age-related macular degeneration (P = .07) and/or diabetes (P = .006). When applied to the independent sample of 145 patients, these five characteristics classified the patients into three groups in which the probabilities of substantial improvement were 85%, 34%, and 3%, thus verifying the discriminatory power of the prediction rule. CONCLUSIONS: Preoperative data can identify patients who are likely to have improvements in visual function after cataract surgery. Such findings may be useful in the selection of patients for this high-volume procedure.

Activities of Daily Living↗
PubMed1995

Serum zinc and serum lipid profiles in 778 adults.

There has been increasing use of high-dosage zinc supplementation in the population, in particular as a potential treatment for age-related macular degeneration. We examined the relationship between fasting serum zinc and serum lipid levels in 778 adults, aged 22 to 80 years, who were control subjects in a multicenter, clinic-based case-control study. The samples were taken during 1987 to 1990, a time when vitamin/mineral supplementation was becoming increasingly common. We found that higher serum zinc levels, most notably those above the highest quintile, were associated with higher levels of total serum cholesterol, low-density-lipoprotein cholesterol, and triglycerides. No significant trend was noted for high-density-lipoprotein cholesterol. Previous studies demonstrated that high-dosage zinc supplements raise serum zinc levels. The possibility that use of such supplements can adversely affect serum lipid profiles suggests that chronic ingestion of such supplements should not be done without adequate medical supervision.

Adult↗
PubMed1994

Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group.

OBJECTIVE--To evaluate the relationships between dietary intake of carotenoids and vitamins A, C, and E and the risk of neovascular age-related macular degeneration (AMD), the leading cause of irreversible blindness among adults. DESIGN--The multicenter Eye Disease Case-Control Study. SETTING--Five ophthalmology centers in the United States. PATIENTS--A total of 356 case subjects who were diagnosed with the advanced stage of AMD within 1 year prior to their enrollment, aged 55 to 80 years, and residing near a participating clinical center. The 520 control subjects were from the same geographic areas as case subjects, had other ocular diseases, and were frequency-matched to cases according to age and sex. MAIN OUTCOME MEASURES--The relative risk for AMD was estimated according to dietary indicators of antioxidant status, controlling for smoking and other risk factors, by using multiple logistic-regression analyses. RESULTS--A higher dietary intake of carotenoids was associated with a lower risk for AMD. Adjusting for other risk factors for AMD, we found that those in the highest quintile of carotenoid intake had a 43% lower risk for AMD compared with those in the lowest quintile (odds ratio, 0.57; 95% confidence interval, 0.35 to 0.92; P for trend = .02). Among the specific carotenoids, lutein and zeaxanthin, which are primarily obtained from dark green, leafy vegetables, were most strongly associated with a reduced risk for AMD (P for trend = .001). Several food items rich in carotenoids were inversely associated with AMD. In particular, a higher frequency of intake of spinach or collard greens was associated with a substantially lower risk for AMD (P for trend < .001). The intake of preformed vitamin A (retinol) was not appreciably related to AMD. Neither vitamin E nor total vitamin C consumption was associated with a statistically significant reduced risk for AMD, although a possibly lower risk for AMD was suggested among those with higher intake of vitamin C, particularly from foods. CONCLUSION--Increasing the consumption of foods rich in certain carotenoids, in particular dark green, leafy vegetables, may decrease the risk of developing advanced or exudative AMD, the most visually disabling form of macular degeneration among older people. These findings support the need for further studies of this relationship.

Aged↗
PubMed1994

Improved visual function and attenuation of declines in health-related quality of life after cataract extraction.

OBJECTIVE: To measure the effect of cataract extraction and lens implantation on elderly persons' health-related quality of life and on their ability to perform visual activities. DESIGN: Evaluations of health status were conducted preoperatively and at 3 and 12 months after surgery on patients scheduled for cataract extraction. SETTING: Patients were enrolled from the General Eye Service of the Massachusetts Eye and Ear Infirmary and 33 Boston practices. PATIENTS: The cohort consisted of 464 patients aged 65 years or older who were identified from the surgical schedule of the Massachusetts Eye and Ear Infirmary. At 3 to 12 months after surgery, 458 (99%) of the participants were successfully contacted. Health-related quality of life data were available for 419 (90%) to assess changes after surgery. MAIN OUTCOME MEASURES: Ophthalmologic examinations were performed preoperatively and during the follow-up period. The Activities of Daily Vision Scale (ADVS) and the Medical Outcomes Study 36-item short from (SF-36) were administered before surgery and at 3 and 12 months postoperatively to assess changes in health status. RESULTS: At 12 months after surgery, 95% of patients had improved Snellen visual acuity, 80% had improved ADVS scores, but only 36% had improved SF-36 physical functioning. Average scores on seven of eight SF-36 subscales worsened at 12 months. Patients with improved ADVS scores had significantly smaller declines across all SF-36 dimensions except for role limitations due to emotional problems. CONCLUSION: Improved visual function after cataract surgery was associated with better health-related quality of life, suggesting that age-related declines in health may be attenuated by improvements in visual function.

Activities of Daily Living↗
PubMed1994

The role of lipids in the detection of lupus anticoagulant by the dilute Russell Viper venom test: are platelets or reagents containing hexagonal HII phases necessary?

Liposomes prepared from rabbit brain extracts (RBE) and individual pure lipids (high phosphatidyl serine content, HIPS) were compared with frozen-thawed platelets (PLTS) in the dilute Russell Viper venom time (dRVVt). While all three preparations demonstrated sensitivity to lupus anticoagulant (LA) the highest detection rate was seen with RBE. For confirmation of LA, high concentration RBE achieved the most efficient correction of the defect. Electron microscopy and particle sizing showed RBE to be small, discrete liposomes, whereas HIPS and PLTS were aggregates of larger diameter particles. Low-angle X-ray diffraction showed no evidence of hexagonal HII phase. There appears to be no specific requirement either for platelets or for reagents containing hexagonal HII phases in the dRVVt. The dRVVt can be optimized by incorporating a simple dilute rabbit brain lipid mixture for detection of LA and a concentrated mixture as a correcting reagent.

Animals↗