Biomedical subjects
Publications and source records attributed to D H Char.
We used in vitro bromodeoxyuridine to analyze the labeling indexes of conjunctival cells in several external eye diseases. Patients with superior limbic keratoconjunctivitis, squamous cell carcinoma of the conjunctiva, drug-induced pseudopemphigoid, and Stevens-Johnson syndrome had increased conjunctival DNA synthesis.
We retrospectively studied 42 men with acquired immunodeficiency syndrome-related Kaposi's sarcoma of the conjunctiva or eyelids who were treated with radiation. Forty-nine sites were treated, 35 (71%) of which involved the eyelids, 12 (24%) the conjunctiva, and two (4%) both the eyelids and conjunctiva. Group 1 consisted of 31 sites treated with a single dose of 800 cGy and group 2 consisted of 18 sites treated with a multiple-fraction regimen and total doses between 1500 and 3600 cGy. The response and recurrence rates in the two groups were similar. One patient from group 2 died within 1 month of treatment and was not included in the analysis. The lesions improved in all cases. A complete response was obtained in 10 (32%) of the 31 lesions in group 1, compared with four (22%) of 18 lesions in group 2. A partial response was obtained in 21 (68%) of 31 lesions in group 1, compared with 13 (72%) of 18 lesions in group 2. Expected minor reactions in the treatment field, primarily loss of cilia, were comparable in the two groups. No serious complications were noted. Recurrence occurred in seven (22%) of the 31 sites in group 1 (six patients) and seven (39%) of the 18 sites in group 2 (six patients). The results suggest that a single treatment of 800 cGy is a safe and effective palliative therapy for ophthalmic acquired immunodeficiency syndrome-related Kaposi's sarcoma.
PURPOSE: The purpose of this study is to identify clinical, ultrasonographic, and fluorescein angiographic features of extramacular disciform lesions that allow differentiation from uveal tumors. METHODS: This was a retrospective study of 19 patients referred to our ocular oncology unit with a possible malignancy who had a diagnosis of an extramacular disciform lesion made after complete evaluation. RESULTS: The level of accuracy for each diagnostic technique alone was as follows: clinical (79%), ultrasonography (83%), and angiography (83%). Fluorescein angiography had limited utility because of severe media opacities in seven cases. No tumor developed an intraocular malignancy during the follow-up period. CONCLUSION: A combination of the above, noninvasive techniques can be used to correctly diagnose extramacular disciform lesions.
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A patient with recurrent squamous cell carcinoma of the conjunctiva was referred with 20/20 vision in an eye with obvious intraocular extension. A modified iridocyclochoroidectomy was performed and the tumour was removed. Three and a half years later the patient's vision is 20/30 and there is no recurrence. This is the first case in which an eye has been successfully salvaged with documented intraocular squamous cell carcinoma of the conjunctiva.
Monoclonal antibodies and flow cytometry were used to study lymphocyte, monocyte and tumor cell antigen expression in uveal melanoma. Forty-one melanomas were studied after various forms of treatment. An antimelanoma antibody, 13A3E, stained 81.7% of the cells. Tumors treated with helium ions or 125I plaques had 13A3E staining reduced to 62.5%, p = 0.011. HLA-A,B,C stained 85.4%, and HLA-DR stained 7.0% of the cells. T cells (CD3 positive) comprised 4.5% (range 0.1-29.2%) of total cell population. Natural killer (NK) cells, B cells and macrophages were present in small numbers (mean less than 2.5% in each case). Tumors with numerous T cells (greater than 5%), were used for T cell subtype studies. The mean helper/inducer (CD4) to cytotoxic/suppressor (CD8) ratio was 1.00 (range 0.11-3.15). CD8 decreased, and CD4 increased with age in unirradiated tumors (p less than 0.02).
In three cases of benign pigmented lesions (one melanocytoma and two pigment epithelial adenomas) there was evidence of tumor growth and the lesions were referred to us as uveal melanomas. The fine needle aspiration biopsy specimens were correctly interpreted in the operating room as being benign tumors. The pigment granules in these benign pigmented lesions are much larger than are observed in uveal melanomas. When they were visible through the heavy pigmentation, the cellular detail appeared benign. In two cases the tumors were successfully resected with cyclochroidectomy techniques and the visual outcome was good. The third eye was studied after it had been removed at another institution. Fine needle aspiration biopsy can often differentiate a benign-simulating pigmented lesion from uveal melanoma.
We detected seven tumors with magnetic resonance imaging, which demonstrate some of the uses and limitations of this diagnostic technique. In one patient, the correct diagnosis of extraocular extension was demonstrated with magnetic resonance imaging when both clinical and ultrasonographic data were not diagnostic. In another case, an extremely small area of extraocular extension was detected with ultrasound evaluation but was not noted on magnetic resonance imaging. Magnetic resonance imaging is highly reliable in the detection of intraocular tumors. In pigmented uveal melanomas it is both sensitive and highly specific. In amelanotic processes magnetic resonance imaging can identify a mass but cannot always adequately characterize it. Further experience will be necessary to determine the proper role of magnetic resonance imaging in the evaluation of uveal tumors.
In a case-control study, we explored a potential association between uveal melanoma and reproductive factors in women. Responses from telephone interviews of 186 women diagnosed with uveal melanoma were compared with responses of 423 women without this disease. All women resided in 11 U.S. western states. We observed a decreased risk of uveal melanoma for women who had ever been pregnant [relative risk (RR) = 0.60, 95% confidence interval (CI) = 0.37 -0.95], with an increase in this protective effect with more live births after adjustment for age, menopausal status, eye color, and skin sensitivity to the sun (1-2 births, RR = 0.47,95% CI 0.29-0.78; 3-4 births, RR = 0.38, 95% CI = 0.22-0.64; 5 or more births, RR = 0.33, 95% CI = 0.15-0.71). The largest effect was observed between nulliparous and parous women. No other reproductive factors, including use of oral contraceptives or postmenopausal estrogens, were shown to be related to risk for uveal melanoma. We conclude that most reproductive factors in this population play little or no role in the etiology of uveal melanoma. The association with number of live births must be confirmed in other studies to assure that it is unrelated to confounding factors not measured in this study.
Techniques for the measurement of bromodeoxyuridine (BrdUrd) positive cells generally include either microscopic evaluation of paraffin embedded sections or measurements on cell suspensions using a fluorescent activated cell sorter. The accuracy of these measurements and their correlations can be affected by a number of technical and intrinsic tumor factors. Extrinsic parameters including degree of necrosis and tumor growth fraction are less easily analyzed in BrdUrd stained material. Retinoblastoma tumor cell cycling was prospectively studied in 11 children using in vivo and one child using in vitro BrdUrd. BrdUrd measurements were made by staining cell suspensions or sections of paraffin embedded tumor and analyzing by microscopy. Approximately 14% of viable cells were in the synthesis-phase of the cell cycle. The correlation between BrdUrd in cell suspensions and BrdUrd in paraffin embedded sections did not reach significance (r = 0.48). DNA analysis of these tumors was also performed using flow cytometry. Nine tumors were found to have a normal diploid DNA content, one had a G1 peak below the diploid control, two had a G1 peak above the diploid control, and one had two G1 peaks (a diploid and a hyperdiploid peak). There was no correlation between abnormal DNA content and the percent of cells in synthesis.
Fortunately, most patients with thyroid-related eye disease have mild ocular involvement that spontaneously involutes. Less than 5% of patients with hyperthyroidism will develop sufficiently severe ocular abnormalities that will require surgical intervention. Most patients with thyroid eye findings should be symptomatically managed. Some will require use of either topical drops or oral steroids to alleviate their eye problems. In approximately one half of those patients who present acutely with severe thyroid orbital finding, nonsurgical therapies will be sufficient to control their eye disease. In the other half, eventually multiple surgical procedures may be required, and as discussed previously, the timing and sequence of those procedures are crucial to achieve optimal results.
To determine whether there were more prior cancers in uveal melanoma patients than in a geographically matched control group, the authors compared the history of prior cancer in 407 uveal melanoma patients who lived in the western United States with that of 870 control subjects. Control subjects were selected by random digit dial and frequency-matched for age at diagnosis of patient, race, and sex. Fifty-one (12.5%) patients and 86 (9.9%) control subjects reported skin cancers whereas 25 (6.1%) patients and 47 (5.4%) control subjects reported other cancers. No statistically significant elevated estimates of relative risk (RR) were found for uveal melanoma with history of skin cancer in either men (RR = 1.4, 95% confidence interval (CI) = 0.87-2.3) or women (RR = 1.1, 95% CI = 0.58-2.0), or with history of other prior cancer in either sex (men, RR = 1.0, 95% CI = 0.42-2.2; women, RR = 1.1, 95% CI = 0.55-2.1). Data from this study do not support an association between prior cancer and increased risk of uveal melanoma.
Forty-two (16%) of 261 patients with ocular melanoma who were treated with helium ions between January 1978 and November 1986 have developed metastatic disease. The time between start of helium ion treatment and recognition of metastatic disease ranged from 3 to 67 months (median, 27 months). The mean pretreatment tumor height in the patients with metastases was 7.7 mm. All 42 patients who developed metastatic disease have died. The median survival after diagnosis of metastatic disease was 5 months; the longest survival was 49 months. The most common site of metastasis was the liver (n = 34). Four (10%) of the 42 patients with metastases also had local recurrence of the tumor. Multivariate analysis identified three variables that predicted independently the development of metastases and lack of survival. These variables are anterior location of tumor (P = .027), tumor height greater than 5 mm (P = .02), and tumor diameter greater than 10 mm (P = .0075).
Understanding tumor growth patterns has implications for prognosis as well as for response and susceptibility to treatment. The antibody Ki-67 was used as a marker of cycling cells and bromodeoxyuridine (BrdUrd) was used as a marker of proliferating cells to characterize the cycling and proliferative rates of cells from human choroidal melanoma. The BrdUrd labeling indices varied from 0-1.1% and the Ki-67 labeling indices ranged from 0-3.0.3%. Linear regression modeling showed good correlation defined by the equation: Ki-67 index = 0.237 + 1.63 x BrdUrd labeling index with r = 0.919. Correlations between these indices and clinical and histologic parameters were not significant.
A number of approaches are being investigated to increase the prognostic accuracy for uveal melanoma patients; the standard deviation of nucleolar area measurements and the DNA content appear to correlate better with survival than do classic histologic parameters. The utility of performing cytomorphometric measurements on fine needle aspiration (FNA) biopsy samples was prospectively analyzed for 24 eyes containing uveal melanomas that were examined with both 25-gauge FNA biopsy and standard histologic techniques. "Masked" analysis of the cellular composition of the 24 cases showed the presence or absence of epithelioid cells to be accurately predicted on the FNA samples in all cases. Image analysis cytomorphometric measurements of nucleolar area showed marked variability (with r less than 0.4) when FNA and histologic samples from the same case were compared. The relationship between these measurements was affected by cell type, sampling, specimen processing and investigator experience.
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We described a model of orbital myositis that was induced by 12-0-tetradecanoyl-phorbol-13-acetate (TPA) injection into the superior rectus muscle of New Zealand white rabbits. In this study, in vivo 31P magnetic resonance spectroscopy (MRS) was performed with a 4.7 Tesla Oxford (Oxford Instruments, Oxford, England) magnet to monitor the evolution of muscle inflammation in control animals and the response of this model to external beam radiation. 31P MRS showed a dramatic increase in high-energy phosphorus and phospholipid metabolites 48 hr after TPA injection. These spectra were similar to those from implanted allogenic fibroblasts. Within 18-48 hr after a single dose (400 cGy) or sequential doses (3 days at 400 cGy) of orbital irradiation, reduced extraocular muscle swelling and a significant decrease of all 31P metabolites occurred. A decrease (63 +/- 6%) in the signal-to-noise (S/N) ratio of the control inflamed muscle 31P MR spectra increased by 28 days after inflammation. Two days after single-dose radiation, 31P MR metabolites were significantly lower (58 +/- 5%, P less than 0.012) than control spectra. These postradiation spectra mirror the 28-day control spectra and are consistent with previous histologic data that show decreased fibroblastic activity. Change in 31P MRS was a sensitive indicator of treatment response latency.