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Biomedical subjects

J M Seddon

Publications and source records attributed to J M Seddon.

At least 109 records · Page 6Linked to original sources
PubMed1989

Evaluation of prior primary malignancy as a determinant of uveal melanoma. A case-control study.

To examine whether individuals with a history of malignancy are at increased risk for uveal melanoma developing, the authors conducted a case-control study comparing history of prior malignancy among 197 New England cases and 385 matched controls identified by random digit dialing (RDD), and 337 cases residing within the United States and 800 sibling controls. Estimated relative risks for uveal melanoma associated with nonskin cancers were 1.2 (95% confidence interval [Cl], 0.61-2.3) and 0.9 (95% Cl, 0.49-1.5) for RDD and sibling comparisons, respectively. Prior skin malignancy (melanoma and basal or squamous cell types) tended to increase the estimated risk in both groups (case/RDD comparison: relative risk, 1.5; 95% Cl, 0.67-3.5 and case/sibling comparison: relative risk, 1.7; 95% Cl, 0.93-2.9). Among females, history of a malignancy was associated with a higher risk in the case/RDD comparison only (relative risk estimate, 2.2; 95% Cl, 0.97-5.1). These results suggest that the association of prior malignancies with uveal melanoma is weak. Cutaneous malignancies and uveal melanomas may share some common risk factors.

Basal Cell Carcinoma↗
PubMed1989

Evaluation of tumor regression and other prognostic factors for early and late metastasis after proton irradiation of uveal melanoma.

The authors examined the relationship of change in tumor height after proton beam irradiation with the risk of metastasis in 700 patients treated for uveal melanoma before July 1, 1986. Rates of change in tumor height were computed for each patient using follow-up ultrasonographic measures during the first 2 years after treatment. Risk of metastasis was evaluated separately in the first 2 years after treatment when tumor decline was assessed (concurrent metastasis), and 2 years or later after treatment (subsequent metastasis). Using Cox proportional hazards models to adjust for other known risk factors, tumors regressing rapidly were significantly more likely to metastasize concurrently with their regression (P less than 0.05). The opposite was found for subsequent metastasis: tumors with a slow annual decline were more likely to metastasize after 2 years after treatment (P less than 0.05). Substantial changes also were noted in the ability of previously described prognostic factors (largest tumor diameter, tumor height, ciliary body involvement, and patient's age) to predict early and late metastasis. Characteristics placing individuals at high risk of metastasis may change markedly with time after treatment.

Follow-Up Studies↗
PubMed1989

The risk of enucleation after proton beam irradiation of uveal melanoma.

Enucleation after proton beam irradiation of uveal melanomas occurred in 64 (6.4%) of 994 eyes with a median follow-up time of 2.7 years. The median time between irradiation and enucleation in the 64 enucleated eyes was 13 months. The probability of retaining the eye was 95 and 90%, 2 and 5 years postirradiation, respectively. Three percent of eyes were enucleated during posttreatment year 1, and the yearly rate was 1% by the fourth year. No patient had enucleation later than 5 1/2 years posttreatment. The complication most likely to result in enucleation was neovascular glaucoma although this was frequently managed without enucleation. Other common reasons for enucleation were documented or suspected tumor growth and complete retinal detachment with associated loss of vision. The leading risk factors for enucleation were anterior tumor margin involving the ciliary body, tumor height greater than 8 mm, and proximity of the tumor to the fovea. Based on the presence or absence of these factors, 5-year eye retention rates were 99, 92, and 76% for low-, moderate-, and high-risk groups, respectively. Thus, the probability of eye retention after proton beam irradiation is high even among those at greatest risk of enucleation.

Eye Enucleation↗
PubMed1989

A computerized image analysis method for measuring elastic tissue.

A computerized image analysis technique for quantifying area fractions of elastic tissue in light microscopic sections is presented that considers the nonuniform distribution of the elastic tissue. The method uses Verhoeff-van Gieson stained sections. The analysis is stratified vertically in three uniform layers starting at the dermo-epidermal junction and horizontally by two schemes. A standard method consists of five equally spaced measurements. The densest method uses the three areas that contain the most elastic tissue. The area fractions are determined by counting the positive and total pixels (thresholding). A validity test utilizing independent physical measurements demonstrated differences of no more than 1.7%. Reliability tests for reading the same section on different days and adjacent sections showed no significant differences (p less than 0.05) between the readings. Reliability tests of sections using different stain lots and adjacent biopsy sites also did not have significant differences. This method may be particularly useful for studies in which the distribution of the material to be measured may be very uneven, such as in solar elastosis.

Biopsy↗
PubMed1988

Phosphatidylcholine-fatty acid membranes. I. Effects of protonation, salt concentration, temperature and chain-length on the colloidal and phase properties of mixed vesicles, bilayers and nonlamellar structures.

The phase and colloidal properties of phosphatidylcholine/fatty acid (PC/FA) mixed vesicles have been investigated by optical methods, acid-base titration, and theoretically as a function of temperature (5-80 degrees C), molar lipid ratio (0-1), lipid chain length (C14-C18), headgroup ionization (1.5 less than or equal to pH less than or equal to 10), vesicle concentration (0.05-32 mumol vesicle.dm-3, and ionic strength (0.005 less than or equal to J less than or equal to 0.25). Increasing the fatty acid concentration in PC bilayers causes the phase transition temperatures (at 4 less than or equal to pH less than or equal to 5) to rise until, for more than 2 FA molecules per PC molecule, the sample turbidity exhibits only two transitions corresponding to the chain-melting of the 1:2 stoichiometric complexes of PC/FA, and pure fatty acid. The former transition is into a nonlamellar phase and is accompanied by extremely rapid vesicle aggregation (with association rates on the order of Ca approximately 10(7) dm3.mol-1.s-1) and massive lipid precipitation. Fluid-phase vesicles with less than 2 FA per PC associate much more slowly (Ca approximately 10(3) dm3.mol-1.s-1), their aggregation being comparable to that of the ordered-phase liposomes. Under no conditions was the relation between the fatty acid concentration and the vesicle association rate for the fluid-phase vesicles linear. In contrast to the X-ray diffraction data, optical measurements reveal a 'pretransitional region' between the chain-melting temperature of the PC component and the temperature at which the gross transformation into a nonlamellar phase sets in. This is seen for all lipid mixtures investigated. On the relative temperature scale, lipids with different chain lengths behave qualitatively similarly; however, the effective association constants determined for samples of constant lipid concentration seem to decrease somewhat with the number of CH2 groups per chain. Fatty acid protonation, which yields electrically neutral bilayers, invariably increases the rate of vesicle association; we have measured, for example, Ca approximately 10(2) at pH approximately 7 and Ca approximately 10(7) dm3.mol-1.s-1 at pH approximately 4). Protonation of the phosphatidylcholine phosphate groups, which causes a net positive charge to accumulate on the lipid vesicles, initially increases (Ca approximately 10(8) dm3.mol-1.s-1) but ultimately decreases (Ca approximately 10(7) dm3.mol-1.s-1) the rate of association between PC/FA (1:2) mixed vesicles.(ABSTRACT TRUNCATED AT 400 WORDS)

Chemical Phenomena↗
PubMed1988

The incidence of eye injuries in New England adults.

A population-based study examined the incidence of eye injuries among New England adults and its association with demographic characteristics and risk-taking behaviors. In 3253 random digit-dialed telephone interviews, 26 adults reported 27 eye injuries during the preceding year, yielding a rate of 9.75 eye injuries per 1000 New England adults. Fifty-nine percent of eye injuries occurred at work. Men had a risk of eye injuries 5.5 times that of women and there was a steep linear decline in eye injury rates with advancing age. Individuals who had other, noneye injuries during the preceding year and individuals who had recently driven after drinking, used marijuana, received a ticket for a moving violation, or not worn seat belts had higher rates of eye injury, but these elevated rates were not statistically significant. Educational and preventive efforts to avoid eye injuries should be directed toward young males in high-risk occupations.

Adolescent↗
PubMed1988

Conservative treatment of uveal melanoma: probability of eye retention after proton treatment.

Enucleation was performed after proton treatment in 57 of 1006 (5.7%) uveal melanoma patients treated with proton beam therapy at the Harvard Cyclotron Laboratory between July 1975 and December 31, 1986. Only 2% of 99 patients with small tumors and 4% of 566 patients with intermediate size tumors underwent enucleation after treatment; 10% of 341 patients with large tumors lost the treated eye. No eyes were removed after 52 months, with 89% of enucleations performed during the first 36 months after treatment. Eye retention rates at 60 months were 89.1 +/- 3.0% for the entire group, and 97 +/- 3.7%, 92.7 +/- 3.1%, and 78.3 +/- 7.0% in patients with small, intermediate, and large tumors, respectively. Significantly greater enucleation rates were observed in patients with large tumors than in those with intermediate tumors (p = less than .0001), in patients with tumor height greater than 8 mm relative to those with tumors less than or equal to 8 mm, p = (less than .0001), with tumor diameter greater than 16 mm compared to less than or equal to 16 mm, (p = less than .0001), and with tumor involvement of the ciliary body compared to involvement of the choroid only (p = less than .0001). Possible strategies to decrease the likelihood of enucleation in patients at apparently increased risk of losing the eye after conservative therapy, that is, those with large tumors involving the ciliary body, might include a lower total dose, a more protracted treatment course, or a lower radiation dose and adjuvant treatment with chemotherapy and/or immunotherapy, with hyperthermia, or with other radiation sensitizers.

Actuarial Analysis↗
PubMed1988

Comparison of transillumination and histologic slide measurements of tumor diameter in uveal melanoma.

Tumor size is an important prognostic factor for deaths due to uveal melanoma. The objectives of this study are: (1) to determine the association between largest tumor diameter assessed by clinical transillumination and largest tumor diameter assessed by measurement of the histologic slide; (2) to predict a clinical transillumination diameter for each enucleation specimen based on the best combination of histologic variables--diameter, height, location, and tumor shape; and (3) to use the predicted transillumination diameter in place of histologic diameter measurement as a prognostic factor for patients treated by enucleation in order to reevaluate previously reported survival outcomes for patients treated by proton beam and enucleation. Comparison of measurements on 40 eyes indicated that transillumination largest diameter measurements were larger than histologic slide measurements (mean difference, 2.87 mm). Multiple linear regression analysis yielded the following equation: transillumination diameter = [4.73 + (0.58 X histologic diameter) + (0.38 X histologic height) + (1.87 X anterior location)]. Using the actual and predicted transillumination measurements, the results of this study support a previously published report on these data: treatment type, tumor size, and location were predictive of melanoma-related deaths, metastases, and all deaths.

Evaluation Studies as Topic↗
PubMed1988

Metastasis from uveal melanoma after proton beam irradiation.

The incidence of metastasis and prognostic factors for metastasis in 780 consecutive patients with uveal melanomas treated with proton beam irradiation were evaluated. Metastasis developed in 64 patients (8%). The median time from treatment to the diagnosis of metastasis was 2.1 years (range, 3 months to 7.3 years). The liver was primarily involved in 58 (90%) patients. The 5-year cumulative probability of metastasis developing was 20%. Prognostic factors for metastasis developing were quite comparable to those found for patients treated by enucleation and included largest tumor diameter, involvement of the ciliary body, older age, and extrascleral extension. Surgical localization, tumor height, and elevated liver enzymes before treatment were not important factors in the development of metastasis.

Adolescent↗
PubMed1988

Preliminary results on phosphorus-31 nuclear magnetic resonance evaluation of human uveal melanoma in enucleated eyes.

Clinical evaluation of uveal melanomas by nuclear magnetic resonance (NMR) techniques depends on ascertaining how these tumors characteristically appear in NMR images and spectra. The authors have determined NMR characteristics of suspected uveal melanomas by phosphorus-31 (31P) NMR spectroscopy of freshly enucleated human eyes. Nuclear magnetic resonance examination was performed at 8.45 Tesla within 90 minutes after enucleation. Enucleated eyes were maintained at 4 degrees C in tissue culture medium during the 30 minutes required for transport. Nuclear magnetic resonance spectra were obtained within 10 minutes, a clinically acceptable time, using a two-turn 31P surface coil. Spectral parameters included 10-kHz spectral width, 1024 data points, and 0.5-second recycle delay. Phosphorus-31 NMR spectroscopy allowed differentiation of choroidal melanomas from normal ocular structures. Differentiating features include significant peaks in tumor spectra due to the phosphodiesters glycerol 3-phosphoryl ethanolamine (GPE) and glycerol 3-phosphorylcholine (GPC), and the phosphomonoesters phosphorylethanolamine (PE) and phosphorylcholine (PC). These preliminary data are encouraging and suggest that clinical trials at the lower magnetic field strengths available in NMR imaging systems seem feasible and warrant investigation.

Choroid Neoplasms↗
PubMed1988

The spectrum and burden of ocular injury.

The authors conducted a hospital-based study to ascertain basic, descriptive epidemiologic information about ocular trauma in an urban setting. Over a 6-month period, 3184 patients presenting to our emergency ward with ocular trauma were studied. Severe injuries totaled 5.1% (ruptured globe, intraocular foreign body, hyphema, orbital/facial fracture) and 94.9% were superficial injuries and contusions. A disproportionate burden of severe ocular injury was borne by those less than 15 years of age. The work place accounted for 48% of all injuries and 50% of ruptured globes. Automobile repair-related tasks were specifically associated with injury. Sports injuries, although accounting for 3.4% of all injuries, were responsible for 60% of hyphemas and 10% of ruptured globes. Annual direct and indirect costs for these ocular injuries are estimated conservatively at $5 million and a loss of 60 work years. A large burden of preventable eye trauma is borne by both patients and society.

Adolescent↗
PubMed1988

Interobserver and intraobserver reliability in the clinical classification of drusen.

The interobserver and intraobserver reliability in determining clinical characteristics of drusen were measured in 161 eyes with age-related macular degeneration (AMD). The percent agreement was 76% for the number of drusen; 89% for the presence or absence of soft drusen; 79% for the presence or absence of confluence drusen; 84% for the presence or absence of focal hyperpigmentation; and, 91% for the presence or absence of geographic (areolar) atrophy. Kappa for each of these characteristics ranged from 0.46 to 0.71 in eyes of patients with bilateral nonexudative AMD and from 0.59 to 0.80 in the fellow eye of patients with unilateral exudative AMD (disciform scarring or macular changes associated with choroidal neovascularization). A significant difference could not be shown in the interobserver reliability for each drusen characteristic after stratifying the data into eyes from patients with bilateral drusen and patients with unilateral exudative AMD. The intraobserver reliability for two graders, obtained on approximately 30% of the original study group by repeating these gradings 6 months after the initial gradings, ranged from 85% to 96% with kappas from 0.60 to 0.85 for all drusen characteristics except for number of drusen. These readers demonstrated good interobserver and intraobserver agreement using definitions describing each of these drusen characteristics.

Adult↗
PubMed1988

Drusen characteristics in patients with exudative versus non-exudative age-related macular degeneration.

The drusen characteristics of 38 eyes from 38 patients with bilateral drusen associated with age-related macular degeneration (AMD) were compared in a masked fashion to 89 fellow eyes from 89 patients with unilateral exudative AMD (disciform scarring or choroidal neovascularization). The average age of the drusen group (67.4 years) was significantly less (P = 0.01) than the average age of the unilateral exudative group (72.6 years). Multiple logistic regression was used to compare the drusen characteristics in the two groups, controlling for the age and sex of the patients. Among patients 75 years of age and younger, patients with confluent drusen had an increased risk of having a fellow eye with exudative AMD compared with patients without confluent drusen. Among patients older than 75 years of age, confluent drusen did not significantly differentiate the two study groups, although confluent drusen in this older age group were more often associated with the bilateral drusen group. Focal hyperpigmentation of the retinal pigment epithelium was also associated with the unilateral exudative group. These drusen characteristics should be evaluated in future prospective studies designed to determine which eyes with drusen are at greatest risk for developing the blinding complications of choroidal neovascularization.

Adult↗
PubMed1987

Death from uveal melanoma. Number of epithelioid cells and inverse SD of nucleolar area as prognostic factors.

Criteria for the Callender classification of uveal melanoma are subjective and lead to variations among observers of the same tumor. Two other measures for cell type-the number of epithelioid cells per high-power field (Epi/HPF) and the inverse SD of nucleolar area (ISDNA)-were evaluated as prognostic factors for survival following enucleation for uveal melanoma in 232 patients. Variables significantly related to the number of Epi/HPF were related to ISDNA. Larger, more anteriorly located tumors had a high number of Epi/HPF and a low ISDNA. The two measures were also correlated. Using Kaplan-Meier survival analysis, both measures were related to tumor deaths. Worse prognosis was associated with a higher number of Epi/HPF and a lower ISDNA. Considered together in Cox' proportional hazards analysis, both measures independently predicted outcome. Separately, each measure predicted uveal melanoma-related deaths, in combination with largest tumor dimension, invasion of tumor to the line of transection, and location of the anterior tumor margin. Although ISDNA is the more objective measure of cell type, its practicality compared with other measures of cell type must also be considered.

Adult↗
PubMed1987

Proton and sodium 23 magnetic resonance imaging of human ocular tissues. A model study.

Clinical evaluation of uveal melanomas by magnetic resonance imaging (MRI) techniques depends on developing an understanding of the appearance of these tumors in magnetic resonance (MR) images. We have determined MR characteristics of uveal melanomas by proton (1H) and sodium 23 MRI of freshly enucleated human eyes at 1.5 tesla. The MR images were obtained using two-turn proton and 23Na surface coils, designed to both transmit and receive the radiofrequency signal. Proton MRI techniques included saturation recovery and spin echo; the gradient-recalled echo technique was used for 23Na MRI. Proton and 23Na MR images provide complementary information; contrast between intraocular tumors and vitreous, lens, or subretinal hemorrhage may be varied by using MR pulse sequences that emphasize tissues based on T1, T2, proton, or sodium density values. A combination of proton and 23Na MRI provides differentiation between normal ocular structures and intraocular tumors, as well as associated complications, such as retinal detachments and subretinal hemorrhages.

Eye↗
PubMed1987

Uveal melanomas near the optic disc or fovea. Visual results after proton beam irradiation.

Proximity to the disc and fovea is a risk factor for visual loss after proton beam irradiation of uveal melanomas. Of 562 eyes treated over a 10-year period with pretreatment visual acuity of 20/200 or better, 363 (64.6%) contained tumors within 2 disc diameters (DD) of the disc or fovea. Rates of visual loss after treatment to worse than 20/200 and causes of visual decline were evaluated using Kaplan-Meier analysis. Cumulative rates of visual loss among subjects with tumors near the disc or fovea were 33 and 47% 1 and 2 years after treatment compared to 17 and 28%, respectively, for subjects with tumors located farther from both structures. The leading cause of visual loss in the first year among eyes with tumors near the disc or fovea was retinal detachment. Controlling for other predictors of visual loss to worse than 20/200, location near the disc or fovea was independently related to visual loss primarily due to retinal detachment, cataract, and radiation retinopathy. Despite the unfavorable location of these tumors, over half of patients with 20/200 or better pretreatment visual acuity had useful vision 2 years after treatment.

Cataract↗
PubMed1987

Long-term results of proton beam irradiated uveal melanomas.

The first 128 consecutive patients with uveal melanomas treated with proton beam irradiation were studied in order to evaluate survival and visual acuity status of patients with relatively long-term follow-up. The median follow-up was 5.4 years, and no patient was lost to follow-up. All tumors showed regression. The most recent visual acuity was 20/40 or better in 35% and 20/100 or better in 58%. Eight eyes were enucleated because of complications. Metastasis developed in 26 patients (20.5%) from 3 months to 7 years after treatment. Results indicate that proton irradiation is quite successful for achieving local control of uveal melanomas. A large proportion of the treated eyes maintained useful vision. Five-year follow-up data indicate that proton irradiation has no deleterious effect on the likelihood of the development of metastasis.

Eye Diseases↗