Biomedical subjects

K M Egan

Publications and source records attributed to K M Egan.

At least 19 recordsLinked to original sources

PubMed1992

Occupation and risk of uveal melanoma. An exploratory study.

BACKGROUND: Little is known about the cause of uveal melanoma, the most common primary intraocular malignant lesion in adults. This population-based case-control study evaluated occupational exposures. METHODS: One hundred ninety-seven newly diagnosed cases of uveal melanoma participated. Approximately two control subjects matched for age, sex, and telephone exchange area were selected for each case by random-digit dialing. Data were collected by a structured telephone interview. Two systems of occupational coding were used: an occupation-exposure linkage system and the Bureau of Census data. Conditional logistic regression for matched studies was used to examine various occupational exposures while controlling for previously reported potential confounders and for family income. The occupation-exposure matrix was used to define clusters of cases exposed to a particular chemical group from various occupations. RESULTS: Odds ratios were elevated for agriculture and farming work for both industry and occupation; this was consistent across both classification systems. Elevated odds ratios also were found for occupations involving machine operations, fabrication, assembling, equipment cleaning, and exposure to metal industries. Exposure to alkylating agents and phenols was associated with a lower risk compared with all other exposures. Several self-reported exposures also were studied. Exposures associated with elevated odds ratios were inks, insecticides, gases, radioactive substances, polybromated biphenyls, and chemical solvents. CONCLUSIONS: This exploratory study suggests various occupational associations for uveal melanoma and areas for future research.

Adolescent↗

PubMed1992

Nucleolar organizer regions in iris nevi and melanomas.

The silver staining of nucleolar organizer region-associated proteins is an objective method that has been used to differentiate benign from malignant neoplasms. Recently this method was used to distinguish benign choroidal nevi from malignant choroidal melanomas. We studied 24 iris melanocytic lesions to assess the applicability of this technique for differentiating benign from neoplastic iris tumors. Masked observers determined the number of silver-stained nucleolar organizer region dots per cell for silver-stained specimens. Iris nevi contained a mean of 1.6 silver-stained nucleolar organizer region dots per cell, whereas iris (spindle A and B, spindle B, epithelioid, mixed cell) malignant melanomas contained a mean of at least 3.5 silver-stained nucleolar organizer region dots per cell (P less than .0001). All iris nevi demonstrated counts lower than 1.9, whereas all iris melanomas demonstrated counts greater than 2.8. Silver-stained nucleolar organizer region counts were also compared with the clinicopathologic variables of gender, age, and largest specimen dimension. Only the largest specimen dimension correlated with silver-stained nucleolar organizer region counts (P less than .0029). The silver-stained nucleolar organizer region method is a simple technique for differentiating iris nevi from iris melanomas. The silver-stained nucleolar organizer region technique may aid in the assessment and treatment of iris lesions by confirming the malignancy of biopsy specimens.

Female↗

PubMed1992

Cataract extraction after proton beam irradiation for malignant melanoma of the eye.

We evaluated visual outcome and risk of metastases in patients who underwent cataract extraction after protonbeam irradiation of a uveal melanoma. A total of 84 patients underwent cataract extraction between 2 months and 11 years after irradiation. One year after cataract extraction, approximately half of the patients had visual acuity of 20/100 or better, and approximately one third had an acuity of 20/40 or better. Larger tumor size was highly correlated with poor visual outcome 1 year after extraction. Six patients underwent enucleation after cataract removal, five due to blind, painful eyes and one due to continued growth of a previously undiagnosed ring melanoma. The rate of metastases was not higher among patients who underwent cataract extraction (adjusted rate ratio, 0.83). Results suggest that cataract extraction offers improvement of vision in selected eyes previously irradiated for a uveal melanoma, without adding to the risk of metastases among patients undergoing the procedure.

Adult↗

PubMed1992

Histopathology of proton beam-irradiated vs enucleated uveal melanomas.

The histopathology of eyes with uveal melanoma was compared in a masked fashion in 47 eyes whose primary treatment was enucleation and a matched series of 47 eyes enucleated after proton beam irradiation. Irradiated tumors were more likely to show signs of necrosis (P less than .001) and fibrosis (P = .005) and to have balloon cells present (P = .002). In the irradiated group, mitotic figures were fewer in 40 high-power fields (P = .020), and the prevalence of tumor blood vessel damage (P less than .001) was higher. Changes in the retina were more common in the irradiated series, but damage was usually overlying or in close proximity to the tumor. Based on characteristic changes, the pathologist distinguished irradiated from nonirradiated eyes in 85% of the cases. These findings suggest that irradiation damages tumor cells and blood vessels, and alters the tumor's capacity for cellular reproduction.

Adult↗

PubMed1992

Radiation maculopathy after proton beam irradiation for choroidal melanoma.

PURPOSE: Radiation maculopathy is a microangiopathy of the retina, which is often observed after irradiation of the eye. To quantitatively determine the frequency of anatomic and functional features of this condition, the authors reviewed a large series of patients with choroidal melanomas who were treated by proton beam irradiation. METHODS: Color photographs and/or fluorescein angiograms of 218 patients with paramacular choroidal melanomas were graded by two independent masked readers to determine the frequency of the various lesions of radiation maculopathy. RESULTS: Overall, 194 (89%) of the 218 patients in this study developed some degree of radiation maculopathy. The earliest and most common finding was macular edema, which was observed in 87% of patients, overall, by the end of year 3. Microvascular changes (microaneurysms and/or telangiectasia), intraretinal hemorrhages, and capillary nonperfusion were noted in 76%, 70%, and 64% of eyes, respectively, by the end of postirradiation year 3. Visual acuity was retained at 20/200 or better in 90% of eyes 1 year after irradiation and in 67% of eyes 3 years after treatment. CONCLUSION: Radiation maculopathy is common after proton beam irradiation of paramacular choroidal melanomas. However, ambulatory vision is preserved in many eyes.

Adolescent↗

PubMed1992

Intraocular recurrence of uveal melanoma after proton beam irradiation.

The authors evaluated tumor recurrence as an end point in 1077 uveal melanoma patients treated by proton beam irradiation between 1975 and 1987, with a mean follow-up of 4.0 years. Twenty tumors (1.9%) exhibited definitive growth between 4 months and 66 months after irradiation (median, 19 months): 10 were marginal recurrences, 5 were ring melanomas, 3 were uncontrolled tumors, and 2 were extrascleral extensions. Ten of these eyes were enucleated without further intervention, 2 patients died of metastases soon after the growth was detected, and 8 patients had further conservative therapy. In 5 other patients, tumor growth was suspected but unconfirmed and the eye was enucleated elsewhere; the 5-year probability of local tumor control based on 25 recurrences was 97% +/- 1%. There was a nonsignificant increase in the rate of metastases among patients with documented tumor recurrence (adjusted relative risk, 1.5; 95% confidence interval, 0.66 to 3.4). Results suggest that recurrence of uveal melanomas treated by proton beam therapy is uncommon, but that treatment failure may increase risk of death from metastasis.

Adolescent↗

PubMed1992

Smoking and the risk of early metastases from uveal melanoma.

Smoking is suspected of altering host immunity and may therefore hasten the development of metastases among cancer patients. The authors followed 946 patients with melanomas of the choroid and/or ciliary body who had been treated with proton beam irradiation and who had provided a smoking history during their evaluation before treatment. After a mean follow-up of 33 months, 98 patients were diagnosed with metastatic disease. Metastasis-free survival rates 3 years after irradiation were similar in association with never, past, and current cigarette smoking (86%, 89%, and 90%, respectively; P = 0.90). Rates also were similar with increasing pack-years of exposure and when the product smoked was cigarettes versus pipes or cigars only. Estimates for smoking effects were unchanged after adjusting for established prognostic factors for metastases. Results suggest that smoking does not alter the risk of metastases during the first few years after irradiation of choroidal melanomas.

Adolescent↗

PubMed1992

Evaluation of skin microtopography as a measure of ultraviolet exposure.

A pilot study was conducted to investigate the use of skin microtopography as a semiquantitative noninvasive method for estimating cumulative sun exposure in epidemiologic studies of eye disease. The subjects received a kit through the mail containing materials needed to make a replica of the skin texture of a sun-exposed area of the hand. Each subject previously had undergone a skin biopsy around the same site to evaluate elastotic degeneration, and all were interviewed about past sun exposures. A gradable skin impression was obtained from 96 of 115 (83%) participants after two mailings. The impressions were graded according to the degree of skin texture alteration using standard photographs; interobserver reliability was 0.73 using a weighted kappa statistic. The impression score was correlated most strongly with age (r = 0.53). Independent predictors of higher impression scores (more skin texture changes) were older age, cigar or pipe smoking, less education, lighter iris color, lighter skin color, male gender, and tendency to sunburn. After adjustment for age and the other predictor variables, the biopsy score was not correlated with the impression grade (r = 0.18, P = 0.13). Behaviors indexing sun exposure were not correlated with microtopography. These results suggest that skin microtopography as done in this study reflects aging from intrinsic parameters more than from actinic damage.

Adolescent↗

PubMed1991

A multi-component upstream activation sequence of the Saccharomyces cerevisiae glyceraldehyde-3-phosphate dehydrogenase gene promoter.

The majority of the activation potential of the Saccharomyces cerevisiae TDH3 gene promoter is contained within nucleotides -676 to -381 (relative to the translation initiation codon). An upstream activation sequence (UAS) in this region has been characterized by in vitro and in vivo assays and demonstrated to be composed of two small, adjacent DNA sequence elements. The essential determinant of this upstream UAS is a general regulatory factor 1 (GRF1) binding site at nucleotides -513 to -501. A synthetic DNA element comprising this sequence, or an analogue in which two of the degenerate nucleotides of the GRF1 site consensus sequence were altered, activated 5' deleted TDH3 and CYC1 promoters. The second DNA element of the UAS is a 7 bp sequence which is conserved in the promoters of several yeast genes encoding glycolytic enzymes and occurs at positions -486 to -480 of the TDH3 promoter. This DNA sequence represents a novel promoter element: it contains no UAS activity itself, yet potentiates the activity of a GRF1 UAS. The potentiation of the GRF1 UAS by this element occurs when placed upstream from the TATA box of either the TDH3 or CYC1 promoters. The characteristics of this element (termed GPE for GRF1 site potentiator element) indicate that it represents a binding site for a different yeast protein which increases the promoter activation mediated by the GRF1 protein. Site-specific deletion and promoter reconstruction experiments suggest that the entire activation potential of the -676 to -381 region of the TDH3 gene promoter may be accounted for by a combination of the GRF1 site and the GPE.

Base Sequence↗

PubMed1991

Survival of patients with metastases from uveal melanoma.

The authors evaluated a series of 145 consecutive patients with metastases from uveal melanoma, after proton beam irradiation, to assess the effect of early diagnosis and treatment for metastases on survival. Metastases were diagnosed between 7 weeks and 8.3 years (median, 2.4 years) after proton beam irradiation. Most patients (n = 94) were symptomatic before diagnosis; the remainder were first detected during screening examination. Liver involvement was documented in nearly all patients (n = 136). The majority of patients had died from metastases by the close of the study (n = 137). Significantly longer survival occurred among patients diagnosed during screening examination (P = 0.004) and among young patients (P = 0.03). The majority of patients received some form of treatment for metastases (69%). Median survival was 2.0 months for patients receiving no treatment compared with 5.2 months for those receiving treatment for metastases (P = .0001). However, the overall 1-year survival rate was poor (13%). Prophylactic adjuvant therapy could be explored as a means to increase disease-free survival in patients with uveal melanoma.

Adult↗

PubMed1990

Host factors, UV radiation, and risk of uveal melanoma. A case-control study.

Uveal melanoma threatens life, as well as sight. To evaluate the effect of constitutional factors and UV radiation on the risk of uveal melanoma, 197 cases in New England were compared with 385 matched population controls, identified by random-digit dialing, and 337 cases residing within the United States were compared with 800 sibling controls. In the population-based comparison, estimated relative risks (RRs) of uveal melanoma, after adjustment for other factors, were elevated for the following: ancestry from more northern latitudes with a substantially elevated risk for Northern European ancestry (RR, 6.5; 95% confidence interval [CI], 1.9 to 22.4) and more than a twofold risk for British ancestry (RR, 2.4; 95% CI, 1.1 to 5.1), as compared with Southern European or other Mediterranean heritage; light skin color as compared with dark (RR, 3.8; 95% CI, 1.1 to 12.6); and 10 or more cutaneous nevi as compared with none (RR, 2.7; 95% CI, 1.5 to 4.9). There was a statistically significant trend for increasing risk with more northern heritage and more moles. Southern residence (below latitude 40 degrees N) for more than 5 years also increased risk (RR, 2.8; 95% CI, 1.1 to 6.9), as compared with none. In both comparisons, use of sunlamps was a risk determinant (RR, 3.4; 95% CI, 1.1 to 10.3 with random-digit dialed controls and RR, 2.3; 95% CI, 1.2 to 4.3 with sibling controls, comparing occasional or frequent use to never use), as was intense sun exposure (RR, 1.7; 95% CI, 0.9 to 3.0 and RR, 2.1; 95% CI, 1.4 to 3.2, respectively). However, birthplace below latitude 40 degrees N and outdoor work were associated with a lower risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1990

Relative survival rates after alternative therapies for uveal melanoma.

Survival in a group of 556 patients with uveal melanoma treated by proton beam irradiation with a median follow-up of 5.3 years was compared with that of 238 patients enucleated during the same 10-year period as irradiated patients (July 1975 to December 1984) with a median follow-up of 8.8 years, and 257 patients enucleated during the preceding 10 years (January 1965 to June 1975) with a median follow-up of 17.0 years. Adjustments were made for known prognostic factors including age, tumor location, tumor height, and clinical estimate of tumor diameter (for enucleated patients this was estimated in a regression equation relating histologic to clinical measurement). The overall rate ratio for all cause mortality was 1.2 (95% confidence interval, 0.9-1.6) for the concurrent enucleation series versus proton beam, and 1.6 (95% confidence interval, 1.2-2.1) for the earlier enucleation series versus proton beam. Relative rates of metastatic death, cancer death, and all cause mortality comparing alternative treatments were found to vary with time after treatment. Interval-specific rate ratios were evaluated using proportional hazards models fitted to separate time intervals after treatment. For all three outcomes, rate ratios were over two and statistically significant for the first 2 years after treatment and closer to one and nonsignificant after year 6 comparing the two enucleation groups with proton beam. Results suggest that treatment choice has little overall influence on survival in patients with uveal melanoma.

Adult↗

PubMed1990

An NMR blood test for uveal melanoma?

In a recent article a simple nuclear magnetic resonance (NMR) blood test was suggested for the detection of the presence of cancer. The test's sensitivity to uveal melanoma of both pre- and posttreatment status has been investigated. Cases in this study were 95 patients with uveal melanoma, and controls were 70 participants in an ongoing case control study of retinal eye disease being conducted at the Massachusetts Eye and Ear Infirmary. Proton NMR evaluations at 4.7 T (200 MHz) were performed on plasma obtained from EDTA and citrated blood samples. The average line-width values were calculated from each spectrum. Statistical analysis revealed that mean proton NMR line widths were essentially equal for patients with treated (18.7 Hz) and untreated tumors (18.4 Hz) and for controls (18.5 Hz). Results based on this data set suggest that proton NMR spectroscopy has little predictive power in the detection of uveal melanoma or in the monitoring of therapy.

Adult↗

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↗

PubMed1989

Microbiology of contact lens-related keratitis.

We reviewed 397 cases of microbial keratitis examined at the Massachusetts Eye and Ear Infirmary, Boston, MA, U.S.A., from January 1982 through December 1985. Of these, 136 cases (34%) were related to contact lens use. Extended-wear contact lenses were used by 107 (79%) of these patients. Cosmetic contact lenses accounted for 59 (44%) of lens-related cases, aphakic contact lenses 44 (32%), and therapeutic (bandage) contact lenses 33 (24%). Fifty-three microbial keratitis cases associated with contact lens wear were culture-positive: 28 (52%) were gram-positive, and 19 (36%) were gram-negative. Mixed cultures, fungi, and Acanthamoeba accounted for two cases (4%) each. Pseudomonas aeruginosa was specifically associated with cosmetic soft contact lens use.

Adult↗